Toe walking

Toe walking is a pattern of walking in which a child walks on balls of his or her feet, with no contact between the heels and ground. Most children begin walking at 12 to 15 months of age. Toe walking is common in children who are learning to walk. When children start to learn walking, they try different foot positions, and walking on their toes may be part of this. After the age of 2, however, most children outgrow toe walking and begin to walk with their feet flat on the ground (a normal heel-to-toe pattern). By 3 years of age, children should walk with a heel-toe pattern.

Most children begin walking at 12 to 14 months with their feet flat on the ground. However, there are some children who begin walking on their tip toes instead. This pattern normally disappears within three to six months of learning how to walk. It almost always is completely gone by the end of the third year.

In very rare cases, continuing to toe walk after age 2 may be a sign of an underlying medical condition. In the vast majority of cases, however, persistent toe walking is “idiopathic” which means that the exact cause is not known. A non-idiopathic cause may be cerebral palsy, autism, sensory processing disorder, muscular dystrophy or brain injury. As children learn to walk, some toe walking is to be expected. When this becomes a strong habit that they do not grow out of, or the predominant pattern as they are new walkers, then several issues can arise.

Older children who continue to toe walk may do so simply out of habit or because the muscles and tendons in their calves have become tighter over time.

The following are negative consequences of toe walking:

• Tight ankles or contractures can develop
• Poor balance reactions, frequent falling
• Muscle imbalances “up the chain” meaning decreased hip or core strength due to the different postural alignment
• Difficulty with body mechanics including squatting or performing stairs, secondary to tight calve muscles
• Inability to stand with heels flat on the ground
• Pain in ankles, knees or hips due to faulty mechanics
• Surgery, casting, night splinting or daily bracing may be necessary

While some toe walking should not be alarming, the earlier you intervene, the better. Discuss this with your pediatrician or see a physical therapist who can provide early strategies to stop the cascade of effects that can be seen later.

Idiopathic toe walking in children is not a serious condition. It often resolves spontaneously and does not cause the child significant problems apart from the cosmetic appearance. Normally, your child will not need surgery. In addition to stretching and strengthening, treatments may include repeated casting of feet and ankles, bracing devices, or a combination of the two. More recently, the injection of Botulinum Toxin A (Botox) has been used to weaken the calf muscles, thus preventing tip toe walking. You can discuss these treatment options with your physician. It is important to understand that even though your child may achieve short-term improvement in muscle length and ankle range of motion, these treatments may not always guarantee a normal heel-to-toe walking pattern.

Toe walking key points

• Idiopathic toe walking is when a child continues to walk on their tip toes beyond three years of age.
• Idiopathic toe walking can lead to tight calf muscles and decreased movement of the ankles.
• Treatment for children younger than six years of age include calf stretches, Achilles tendon stretches and sit to stand exercises.
• Treatment for children six years of age and older include calf stretches and other exercises including marching on the spot, walking uphill and on uneven surfaces, heel walking and squats.

Is toe walking just a developmental variation?

Generally, until age 2, toe walking isn’t something to be concerned about. Often, children who toe walk after that do so out of habit. More than half of young children who toe walk will stop doing so on their own by about age 5. Most children toe walk occasionally when they’re cruising around a room (by holding on to furniture), especially if they’re on a bare floor. Some kids keep toe walking, off and on, just for fun. Toe walking out of habit, also known as idiopathic toe walking, sometimes runs in families. The cause of idiopathic toe walking is unknown.

Parents of more than 1,400 children participated in a study conducted in Blekinge County in southeast Sweden. The results, published in Pediatrics in 2012, showed more than half of young children who toe walk stopped doing so on their own by about age 5, and most toe walkers did not have any developmental or neuropsychiatric problems.

Toe walking anatomy

The calf is formed by two major muscles. They are:

• Gastrocnemius muscle. This is the larger calf muscle. Its two parts form the bulge that is visible beneath the skin.
• Soleus muscle. This smaller, flat muscle lies underneath the gastrocnemius muscle.

Both muscles merge at the base of the calf, where they transition into becoming the Achilles tendon. The Achilles tendon then inserts into the calcaneus (heel bone). When you contract your calf muscles, the Achilles tendon pulls on your heel.

In some children who toe walk, this muscle-tendon combination may be shorter at birth, or may shorten over time, which prevents the child from touching his or her heels to the ground and walking flat-footed. However, in most children who toe walk, the muscle-tendon combination is long enough that the child is able to walk with his or her heels down if reminded to do so.

Figure 1. Toe walking anatomy

Footnote: The calf muscles and Achilles tendons work together to help lift your heels when you walk.

Toe walking causes

In the vast majority of children, toe walking is “idiopathic,” which means that the exact cause is unknown. When these children are evaluated by a doctor, their physical exams and neurological tests are normal.

Rarely, toe walking can be the result of a short Achilles tendon (the tendon that links the lower leg muscles to the back of the heel bone), cerebral palsy, muscular dystrophy, or another generalized disease of nerve and muscle. Toe-walking can also be associated with sensory-processing disorder. Sensory processing happens constantly every time we eat, move, or do an activity. Problems arise when the brain is unable to organize this information appropriately – like a traffic jam of information. Sensory-processing disorder can manifest itself in a myriad of ways, depending on which senses are affected. Children with autism also may walk on their toes or the balls of their feet. But as long as your child is growing and developing normally, toe walking in its own is unlikely to be a cause for concern.

Idiopathic toe walking

Toe walking out of habit, also known as idiopathic toe walking, sometimes runs in families. Idiopathic toe walking is when a child continues to walk on their tip toes beyond three years of age. They will often stand with their feet flat on the ground, but when walking or running will prefer to be on their toes. If your child does not outgrow tip toe walking by three years of age, take them to see a health-care professional.

Medical causes

In a smaller number of cases, persistent toe walking can be a sign of an underlying medical condition, such as:

• Cerebral palsy. Toe walking can be caused by a disorder of movement, muscle tone or posture caused by injury or abnormal development in the parts of the immature brain that control muscle function.
• Muscular dystrophy. Toe walking sometimes occurs in this genetic disease in which muscle fibers are unusually prone to damage and weaken over time. This diagnosis might be more likely if your child initially walked normally before starting to toe walk.
• A spinal cord abnormality
• A short Achilles tendon. This tendon links the lower leg muscles to the back of the heel bone. If it’s too short, it can prevent the heel from touching the ground.

Although children with autism-related conditions toe walk more frequently than children who are developing normally, there is no direct link between the two conditions, and their toe walking may be sensory-related.

Toe walking signs and symptoms

Although doctors do not really know why some children prefer to walk on their toes, they do know that idiopathic toe walkers:

• walk on tip toes on both sides
• are constantly balancing on their toes
• are physically able to keep up with other children their age
• walk with straight knees
• will often be able to stand with their feet flat on the ground
• often have a family history of toe walking

Most young children who walk on their toes are able to walk flat-footed when asked to do so. However, many older children who continue to toe walk (usually those over the age of 5 are not able to walk with their heels down. These children may complain about problems wearing shoes or participating in sports or recreational activities that involve wearing roller skates or ice skates.

Some children who toe walk have no specific complaints, but their parents are still concerned about the impact their walking pattern may have on their future function as teenagers and adults.

Toe walking complications

Children who walk on their toes can develop tight calf muscles on the backs of their legs and have decreased movement of their ankles. In addition, the muscles on the front of their legs may become weak. If there is tightness and weakness, your child will have difficulty walking on their heels. Early identification of toe walking can help lead to the prevention of these muscle problems.

Kids who develop stiffness, tightening, and pain in their Achilles tendon can be treated with physical therapy and stretching exercises. Rarely surgery may be required (usually after age 6) if the toe walking is the result of (or results in) tendon stiffness.

Toe walking diagnosis

Your child’s doctor will begin by asking a number of questions, including:

• Were there any pregnancy complications or was your child born prematurely?
• How old was your child when he or she reached developmental milestones such as smiling, sitting, and walking?
• When did the toe walking start? (For example, did it begin when your child started to walk independently or at an older age?)
• Is the toe walking on both sides or only on one side? (Toe walking on just one side may be more concerning to your doctor since it can sometimes indicate a neurological problem.)
• Is there a family history of toe walking?
• What percentage of time is spent walking on the toes?
• If asked, is your child able to walk flat-footed?
• Does your child complain of foot or leg pain, weakness in the legs, or difficulty keeping up with children the same age?

Physical examination

The physical exam will typically begin with your doctor observing your child walk. In order to avoid the “doctor walk” (the patient does his or best to walk properly when the doctor is watching), this may be done even before your child realizes that he or she is being watched.

Your doctor will then ask to see your child’s typical walk (on the toes), followed by his or her “best” walk (walking as flat-footed as possible). In addition to observing the toe walking itself during this time, your doctor will also be evaluating the smoothness of the walk as part of a neurological evaluation.

During the physical exam, your child’s doctor will also:

• Check your child’s feet for abnormalities, including differences between the left foot and right foot.
• Look for differences in leg length and in the size of the thighs and calves.
• Assess if one or both calf muscles are tight by asking your child to move his or her feet and ankles in a number of different ways.
• Check range of motion in the hips and knees.
• Look for any skin abnormalities in the lower extremities and lower back.

Tests

Neurological exam. Some simple neurological tests will help determine if abnormalities in your child’s nervous system could be contributing to the toe walking. The exam will be tailored to your child’s age, developmental level, and ability to cooperate.

During the exam, your child’s doctor will:

• Assess if there is any contracture or excessive tightness of the muscles in the arms or legs.
• Check the strength of the major muscles.
• Check your child’s reflexes by tapping a small rubber hammer or a fingertip on different points on the body.
• Test sensation, or feeling, in the arms and legs.

Other tests. Idiopathic toe walking is a diagnosis of exclusion, meaning that no other problems can be identified from your child’s medical history and physical exam. For this reason, specific tests—such as x-rays, CT and MRI scans, and nerve and muscle tests involving electrode patches or needles electromyography (EMG)—are not usually ordered.

During an EMG, a thin needle with an electrode is inserted into a muscle in the leg. The electrode measures the electrical activity in the affected nerve or muscle.

If the doctor suspects a condition such as cerebral palsy or autism, he or she may recommend a neurological exam or testing for developmental delays.

Toe walking treatment

Treatment for toe walking depends on a number of factors, including:

• The age of your child
• Whether your child is able to walk flat-footed

Treatment for persistent toe walking often involves a period of casting or bracing to help stretch the muscles and tendons in the calves and encourage a normal gait.

Nonsurgical treatment

For children who are 2 to 5 years old and able to walk flat-footed, initial treatment is always nonsurgical.

Nonsurgical treatment may include:

• Observation. Your doctor may recommend simply monitoring your child with regular office visits for a period of time. If he or she is toe walking out of habit, it may stop on its own.
• Serial casting. Your doctor may apply a series of short leg walking casts to help progressively stretch and lengthen the muscles and tendons in the calf and break the toe-walking habit. Serial casting is usually performed over a period of several weeks.
• Bracing. Wearing an ankle-foot orthosis (AFO) can help stretch and lengthen muscles and tendons. An AFO is a plastic brace that extends up the back of the lower leg and holds the foot at a 90 degree angle. Typically, bracing is performed for a longer period of time than casting (months rather than weeks).
• Botox therapy. For certain patients—usually those with a neurologic abnormality that leads to increased muscle tone—an injection of botulinum A toxin (Botox®) may also be given to temporarily weaken the calf muscles. This will allow the muscles to stretch more easily during casting or bracing.

Shoes for your child

Wearing shoes may not correct toe walking. However, appropriate foot wear can help your child bring their heels further down. When selecting shoes for your child, keep in mind the following criteria:

• Choose a high cut shoe with a wide sole which provides good foot support.
• The shoe should be rigid or firm, not flexible in the middle section.
• The back of the heel should be firm.

Home exercises

If your child has idiopathic toe walking, a daily home exercise program can be very helpful. The goal is to stretch the calf muscles and strengthen the muscles on the front of the legs. This will help your child to be able to successfully walk with a heel-to-toe pattern.

If your child’s calf muscles are tight, or ankle motion is limited, you will be shown stretches to do at home with them. These stretches should be followed with activities to help them use their muscles in their new lengthened position.

These exercises will be necessary and beneficial as long as your child demonstrates a tip toe walking pattern. The exercises will vary with their age. The most important part of the exercise program is to remember to have fun with your child!

Stretches and strengthening exercises for children under six years of age

Calf stretch

• Have your child lie on their back on a comfortable surface such as a firm bed.
• With their knee straight and leg supported on the bed, bring your child’s foot upwards, toward their head, bending their ankle.
• Hold the stretch at the end of the movement (that is, as far as your child’s range of motion will permit) for 15 to 30 seconds. This should not be painful for your child.
• Bring your child’s foot back to a normal position. Repeat the exercise 10 times on each leg, daily.

Figure 2. Calf stretch

Achilles tendon stretch

• Have your child lie on their back on a comfortable surface such as a firm bed.
• With their knee bent, bring your child’s foot upwards, toward their head, bending their ankle.
• Hold the stretch at the end of the movement (that is, as far as your child’s range of motion will permit) for 15 to 30 seconds. This should not be painful for your child.
• Bring your child’s foot back to a normal position. Repeat the exercise 10 times on each leg, daily.

Figure 3. Achilles tendon stretch

Sit to stand

• Have your child sit on a children’s sized chair or stool.
• Place your hands below their knees, providing a moderate, constant pressure downwards as a cue to keep their heels on the floor.
• Have your child practice standing up while keeping their heels on the ground.
• Make this exercise fun by playing a game of high five, blowing bubbles, reaching for objects, working in front of a mirror or singing songs.

Figure 4. Sit to stand

Exercises suitable for children ages six years and up

Calf Stretch

• Have your child stand approximately two feet from a wall. Place both of their hands at shoulder height against the wall.
• With their right knee straight, have them step towards the wall with the left foot. They should lean in until a stretch is felt in the back of the right calf. Make sure they keep the heel of the right foot on the ground.
• Hold the stretch for 15 to 30 seconds.
• Repeat the exercise 10 times on each leg, daily.

Figure 5. Calf stretch

Other exercises include:

• Marching on the spot. Have your child bring their knees up high and then land with a flat foot.
• Walking uphill.
• Walking on uneven surfaces such as in a playground or sand.
• Walking on the heels only. Keep the toes off the ground at all times.
• Practicing squats. With feet flat on the floor, hip width apart, have your child slowly lower their body all the way to the floor by bending at their knees and hips but keeping their chest upright.

Figure 6. Squats

Surgical treatment

Toe-walking children over the age of 5, the calf muscles and Achilles tendons may be so tight that walking flat-footed is not possible. For these patients, the doctor may recommend a surgical procedure to lengthen the Achilles tendons. Lengthening the tendons will improve range of motion and allow better function of the foot and ankle.

The specific part of the tendon that is lengthened depends on whether or not the patient’s foot can be positioned flat at the ankle with his or her knee bent. There are several techniques used to lengthen different areas of the tendon. Your doctor will talk with you about which technique is best for your child.

The procedure is usually done on an outpatient basis (no overnight stay). After the tendons are lengthened, while your child is still asleep, your doctor will place his or her legs in short leg walking casts. These are typically worn for 4 to 6 weeks.

Recovery

Physical therapy is usually recommended after both surgical and nonsurgical treatment to help the patient learn to walk flat-footed more consistently. Physical therapy after surgery typically does not begin until the walking casts have been removed.

Toe walking prognosis

Most patients improve over time and are able to participate in normal activities and sports. However, studies show that some children will continue to toe walk—even after serial casting or surgery.

In toe walking

In-toe walking also called “pigeon-toed” or having “intoeing”, is when children who walk with their feet pointing inward. According to Columbia Orthopedics, 2 out of every 1,000 children will in-toe. In-toeing affects boys and girls equally, and is often noted to both legs and it occurs for a variety of reasons, but most cases are corrected on their own as the child grows up. This is why there aren’t many pigeon-toed adults. Parents of children who in-toe often report that their children fall over more frequently than expected.

Most children learn to walk with their feet pointing straight ahead. Some children (and a few adults) walk with their toes pointing in.

There are 3 main causes of in-toe walking:

1. Femoral anteversion: A condition where the hip turns in.
2. Tibial torsion: Where the lower leg turns (shin bone) in when compared to the upper leg.
3. Metatarsus adductus: The bones in the foot turn in.

The most common cause of femoral anteversion is tibial torsion. Tibial torsion usually starts in-utero and disappears by the time the child is 5 or 6 years old. Femoral anteversion can also be started in-utero, and is usually corrected by age 9 or 10. Most of the time, in-toeing corrects itself with no intervention. Special shoes and braces used to be quite common in treating femoral anteversion, however, these have been proven to not be helpful in treating in-toeing.

Most of the time, in-toeing does not cause any problems with sports or leading a normal, healthy lifestyle. It has not been proven to cause arthritis in life, which is a common mis-conception. However, some children fall or trip more often when they are younger secondary to in-toeing. Physical therapy can help with balance reactions, safety awareness and strengthening to decrease the tripping and falling and help promote proper alignment.

If you are worried about your child’s in-toeing, or suspect that it is getting worse, talk with you pediatrician or contact a licensed pediatric physical therapist.

In-toe walking or intoeing key points

• Most children with intoeing do not need treatment as they will self-correct over time.
• Special shoes and braces aren’t usually needed and are only recommended by doctors for rare cases.
• Orthotics are not useful for correcting intoeing.

Figure 1. In toe walking

In-toe walking during infancy

Infants are sometimes born with their feet turning in. This turning occurs from the front part of their foot, and is called metatarsus adductus. It most commonly is due to being positioned in a crowded space inside the uterus before the baby is born.

You can suspect that metatarsus adductus may be present if:

• The front portion of your infant’s foot at rest turns inward.
• The outer side of the child’s foot is curved like a half- moon. This condition is usually mild and will resolve before your infant’s first birthday. Sometimes it is more severe, or is accompanied by other foot deformities that result in a problem called clubfoot.

This condition requires a consultation with a pediatric orthopedist and treatment with early casting or splinting.

In-toe walking in later childhood

When a child is intoeing during her second year, this is most likely due to inward twisting of the shinbone (tibia). This condition is called internal tibial torsion. When a child between ages three and ten has intoeing, it is probably due to an inward turning of the thighbone (femur), a condition called medial femoral torsion. Both of these conditions tend to run in families.

In-toe walking causes

There are three common causes of in-toe walking or intoeing:

1. Tibial torsion –The shinbone (tibia) is the most common twisted bone. The twist can be caused by the way your baby lay in the womb while the bones were still soft. The bone slowly untwists as the child grows. Usually the twist is gone by school age.
2. Femoral anteversion – The thigh bone (femur) can also be twisted inwards. This usually corrects itself, more slowly, by age nine or ten. In some children this doesn’t correct fully and these are the people who walk pigeon-toed as adults.
3. Metartasus adductus – The feet are curved inwards. Most of these children also get better without treatment, but for those few children who have very curved feet, some bracing or special shoes may help in the first few years of life.

Two thirds of children with in-toe walking have an inwards twist to the top of their femur (thigh bone) at the hip. This is called femoral anteversion.

Some children may have an inwards twist to their tibia (shin bone). This is called internal tibial torsion.

In some children in-toe walking may be due to the shape their feet which are curved and tend to hook inwards. This is called metatarsus adductus.

Femoral anteversion

Children are all born with an inward twist in the femur below the hip joint. Most of children grow out of this by the age of two years. Some children take longer and tend to walk with their knees and feet turned inwards. They often like to sit with their legs in the ‘W’ position. In the vast majority of these children, this twist in the bone gradually disappears by the age of 7-8 years.

Treatment with splints, plasters or braces does not affect it, but your doctor may advise you to discourage your child from sitting in the ‘W’ position.

In a very few children, femoral anteversion persists in the long-term. It is never a functional problem, however, and they can participate in sports or other physical activities without problems. In extremely rare cases of teenagers who have a severe twist that causes pain at the hips or knees, an operation may be considered to correct it.

Internal tibial torsion

In-toe walking can often be caused by an inward twist of the tibia (shin bone). This is very common in babies and toddlers and is due to ‘moulding’ of the baby during pregnancy.

It may persist for a few years but gradually disappears as the child grows. Treatment with splints, plasters or braces does not alter it and is unnecessary.

Tibial torsion does not cause any functional problems and children can participate in all physical activities without suffering any long-term problems.

Metatarsus adductus

In-toe walking can sometimes be seen in children who have feet that are curved inwards (pigeon toes). This can also be due to ‘moulding’ during pregnancy. It is often seen in children who tend to sleep face down.

More than 80 percent of children grow out of this by the age of 3-4 years.

If the foot is supple and flexible (the doctor will check that) treatment is not necessary. In some children with more pronounced problems and feet that are less flexible, the doctor may recommend special shoes, splints to be worn at night or, rarely, treatment with plaster casts.

Very few children need an operation for their feet to be straightened. The vast majority of children with metatarsus adductus do not complain of any symptoms, can participate in all physical activities and have no long-term problems.

In-toe walking symptoms

Children who have intoeing or in-toe walking tend to trip a little more at first, but later on are fine. Children with intoeing are just as good at sport and are no more likely to get arthritis or back problems than anyone else. Intoeing should not get worse and your child should be able to take part in all types of physical activity.

If you are concerned about your child’s intoeing, you can take photographs or videos of your child walking every six months to keep a record of the changes. If you think your child’s intoeing is getting worse, a doctor should see them again. Many parents worry that their child will always walk with their feet turned in, however this hardly ever happens. No treatment has been proven to improve a child’s intoeing – it is best to just let it correct itself as your child grows.

In-toe walking treatment

Some experts feel no treatment is necessary for intoeing in an infant under six months of age. For severe metatarsus adductus in infancy, early casting may be useful.

The bone twisting conditions cannot be fixed with braces, shoe inserts or special shoes. These methods were used in the past and have been shown to have no effect. It has been found that the bones correct themselves without any treatment. There is no need to try to modify your child’s walking or sitting. This will not alter their development and can lead to frustration for the child and parent for no reason. Very occasionally your doctor may recommend a brace for a special reason.

Studies show that most infants who have metatarsus adductus in early infancy will outgrow it with no treatment necessary. If your baby’s intoeing persists after six months, or if it is rigid and difficult to straighten out, your doctor may refer you to a pediatric orthopedist who may recommend a series of casts applied over a period of three to six weeks. The main goal is to correct the condition before your child starts walking.

Intoeing in early childhood often corrects itself over time, and usually requires no treatment. But if your child has trouble walking, discuss the condition with your pediatrician who may refer you to an orthopedist. A night brace (special shoes with connecting bars) was used in the past for this problem, but it hasn’t proven to be an effective treatment. Because intoeing often corrects itself over time, it is very important to avoid nonprescribed “treatments” such as corrective shoes, twister cables, daytime bracing, exercises, shoe inserts, or back manipulations. These do not correct the problem and may be harmful because they interfere with normal play or walking. Furthermore, a child wearing these braces may face unnecessary emotional strain from her peers.

Nevertheless, if a child’s intoeing remains by the age of nine or ten years old, surgery may be required to correct it.

Duchenne muscular dystrophy

Duchenne muscular dystrophy is one of the most severe forms of inherited muscular dystrophies that is characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact. Duchenne muscular dystrophy primarily affects the skeletal muscles, which are used for movement, and heart (cardiac) muscle. Duchenne muscular dystrophy occurs almost exclusively in males, but in rare cases it can affect girls. Duchenne muscular dystrophy does not exhibit a predilection for any race or ethnic group.

Duchenne muscular dystrophy is one of four conditions known as muscular dystrophies or dystrophinopathies. The other three diseases that belong to muscular dystrophies group are Becker muscular dystrophy, a mild form of Duchenne muscular dystrophy; an intermediate clinical presentation between Duchenne muscular dystrophy and Becker muscular dystrophy; and Duchenne muscular dystrophy-associated dilated cardiomyopathy (heart-disease) with little or no clinical skeletal, or voluntary, muscle disease.

Duchenne muscular dystrophy and Becker muscular dystrophy have similar signs and symptoms and are caused by different mutations in the same DMD gene or dystrophin gene. The two conditions differ in their severity, age of onset, and rate of progression. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood, usually between ages 2 and 3 and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by adolescence. The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate.

Duchenne muscular dystrophy is usually first diagnosed when a child is three to four years old, although symptoms are common earlier than this. Early signs of Duchenne muscular dystrophy include:

• toe-walking – children start walking on their tip toes
• larger than normal calf muscles, which is called pseudohypertrophy
• a waddling type of walk
• inability to run or climb stairs
• an unusual way of getting off the floor, called a Gowers sign.

Some children with Duchenne muscular dystrophy also have delay in their speech development, and many will not walk until after 18 months of age.

Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called cardiomyopathy. This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. These heart problems worsen rapidly and become life-threatening in most cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond.

A related condition called X-linked dilated cardiomyopathy is a form of heart disease caused by mutations in the same gene as Duchenne and Becker muscular dystrophy, and it is sometimes classified as subclinical Becker muscular dystrophy. People with X-linked dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing.

The estimated incidence is 1 in 3600 male live-born infants. In Europe and North America, the prevalence of Duchenne muscular dystrophy is approximately 6 per 100,000 individuals ¹⁾. Some studies have estimated the prevalence of DMD as 2 per 10,000 in the United States. Between 400 and 600 boys in the United States are born with Duchenne muscular dystrophy and Becker muscular dystrophy each year.

Current therapy is centered on treatment with glucocorticoids and physiotherapy to prevent orthopedic complications ²⁾.

Duchenne muscular dystrophy key points to remember

• Duchenne muscular dystrophy is a progressive disease causing increasing weakness of the muscles of the arms and legs, the breathing muscles and the heart.
• Duchenne muscular dystrophy can be inherited or may occur in only one family member. Genetic testing is recommended, especially if you have a family history of neuromuscular disease.
• It is essential to keep regular appointments with a neurologist, physiotherapist and other health care professionals.
• Duchenne muscular dystrophy is a progressive disorder and your child’s needs will increase as they get older.

Can my son attend a normal kindergarten and school?

Most children with Duchenne muscular dystrophy are able to attend mainstream kindergartens and schools, though appropriate adjustments need to be made for their physical and learning needs. Your child will have an Individualised Learning Plan and may qualify for additional support, in the form of an aide or school modifications.

Are any learning problems associated with Duchenne muscular dystrophy?

Up to one third of boys with Duchenne muscular dystrophy have a learning problem, but these are unlikely to be significant. There are also increased risks of ADHD, dyslexia and cognitive skills.

What is Gower’s sign?

Gower’s sign is an unusual way of standing up from the floor, where a child uses their upper limbs to compensate for weak lower limbs. A child will push themselves up on their arms and knees, then use their hands to ‘walk up’ their legs before standing upright.

Duchenne muscular dystrophy causes

Mutations in the DMD gene (dystrophin gene) located on chromosome Xp21, cause the Duchenne muscular dystrophy and Becker muscular dystrophy ³⁾. Most mutations are deletions and duplications, and this accounts for 70% to 80% of the mutations. Point mutations are seen in 20% to 30% of patients. DMD gene is the largest known human gene (containing 79 exons of a coding sequence and 2.5 Mb of DNA), provides instructions for making a protein called dystrophin. This protein is located primarily in muscles used for movement (skeletal muscles) and in heart (cardiac) muscle, where it helps stabilize and protect muscle fibers. Small amounts of dystrophin are present in nerve cells in the brain ⁴⁾. Dystrophin may also play a role in chemical signaling within cells.

In skeletal and cardiac muscles, dystrophin is part of a group of proteins (a protein complex) that work together to strengthen muscle fibers and protect them from injury as muscles contract and relax. The dystrophin complex acts as an anchor, connecting each muscle cell’s structural framework (cytoskeleton) with the lattice of proteins and other molecules outside the cell (extracellular matrix). The dystrophin complex may also play a role in cell signaling by interacting with proteins that send and receive chemical signals.

Little is known about the function of dystrophin in nerve cells. Research suggests that the protein is important for the normal structure and function of synapses, which are specialized connections between nerve cells where cell-to-cell communication occurs.

Mutations in the DMD gene alter the structure or function of dystrophin or prevent any functional dystrophin from being produced. Muscle cells without enough of this protein become damaged as muscles repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies. Mutations that lead to an abnormal version of dystrophin that retains some function usually cause Becker muscular dystrophy, while mutations that prevent the production of any functional dystrophin tend to cause Duchenne muscular dystrophy.

Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, these conditions are classified as dystrophinopathies.

Duchenne muscular dystrophy inheritance pattern

Duchenne muscular dystrophy is inherited in an X-linked recessive pattern; however, approximately 30% of cases are due to new mutations ⁵⁾. The DMD gene associated with Duchenne muscular dystrophy is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause Duchenne muscular dystrophy. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause Duchenne muscular dystrophy. Because it is unlikely that females will have two altered copies of the DMD gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In many cases, an affected male inherits the mutation from his mother, who carries one altered copy of the DMD gene. The remainder of cases probably result from new mutations in the gene in affected males and are not inherited.

In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Carrier females show no evidence of muscular weakness; however, symptomatic female carriers have been described. About 2.5% to 20% of female carriers (females who carry a DMD gene mutation) may have muscle weakness and cramping. This can be explained by the Lyon hypothesis in which the normal X chromosome becomes inactivated, and the X chromosome with the mutation is expressed ⁶⁾. These symptoms are typically milder than the severe muscle weakness and atrophy seen in affected males. Females who carry a DMD gene mutation also have an increased risk of developing heart abnormalities including cardiomyopathy.

Female carriers can become symptomatic if they are associated with Turners syndrome (45X) or mosaic Turner karyotype, balanced X autosome translocations with breakpoints within the dystrophin gene and preferential inactivation of the normal X, and females with a normal karyotype but with nonrandom X chromosome inactivation with diminished expression of the normal dystrophin allele ⁷⁾.

Figure 1. Duchenne muscular dystrophy X-linked recessive inheritance pattern

People with specific questions about genetic risks or genetic testing for themselves or family members should speak with a genetics professional.

Resources for locating a genetics professional in your community are available online:

• The National Society of Genetic Counselors (https://www.findageneticcounselor.com/) offers a searchable directory of genetic counselors in the United States and Canada. You can search by location, name, area of practice/specialization, and/or ZIP Code.
• The American Board of Genetic Counseling (https://www.abgc.net/about-genetic-counseling/find-a-certified-counselor/) provides a searchable directory of certified genetic counselors worldwide. You can search by practice area, name, organization, or location.
• The Canadian Association of Genetic Counselors (https://www.cagc-accg.ca/index.php?page=225) has a searchable directory of genetic counselors in Canada. You can search by name, distance from an address, province, or services.
• The American College of Medical Genetics and Genomics (http://www.acmg.net/ACMG/Genetic_Services_Directory_Search.aspx) has a searchable database of medical genetics clinic services in the United States.

Duchenne muscular dystrophy symptoms

Duchenne muscular dystrophy usually becomes apparent early during childhood. Weakness related to Duchenne muscular dystrophy selectively affects the limb muscles close to the trunk before the ones far from it; the legs are affected before the arms. Development in the first few years of life is typically normal, with milestones achieved at a slightly delayed if not normal rate. Growth velocity with Duchenne muscular dystrophy is typically slower than normal in the first years of life, leading to short stature. Mild hypotonia in an infant may be present, and poor head control in an infant may be an initial sign. Patients do not have atypical facies, but with the onset of facial muscle weakness, a transverse or horizontal sign may be seen in later childhood. Weakness and difficulty in ambulation in typically first noted between 2 and three years of life. This manifests as toe walking, difficulty running, climbing up stairs, and frequently falling. Weakness is more pronounced in proximal than distal muscles and the lower limb more than the upper limb.

Boys with Duchenne muscular dystrophy are often late walkers. Patients must use a wheelchair by the age of 12. In ambulatory children, an increased incidence of fractures is noted as a consequence of the frequent falls.

Affected children develop weakness and wasting (atrophy) of the muscles closest to the trunk (proximal muscles) such as those of the upper legs and pelvic area and upper arms and shoulder area. However, a few other muscles appear disproportionally bulky. As the disease progresses, muscle weakness and atrophy spread to affect the lower legs, forearms, neck and trunk. The rate of progression is quite similar from person to person but individual variation may happen.

In children with Duchenne muscular dystrophy, initial findings may include delays in reaching developmental milestones such as sitting or standing without assistance; toe walking; an unusual, waddling manner of walking (Trendelenburg gait); difficulty climbing stairs or rising from a sitting position (Gower’s sign); and repeated falling. Toddlers and young children may seem awkward and clumsy and may exhibit abnormal enlargement of the calves due to scarring of muscles (pseudohypertrophy). Aside from the calves, hypertrophy of the tongue and muscles of the forearm may be seen but are less classical. Parents may be falsely encouraged by an apparent improvement between the ages of 3 and 5, but this may be due to natural growth and development. As the disease progresses, additional abnormalities may develop such as progressive curvature of the spine (scoliosis or lumbar lordosis), wasting of thigh and pectoral muscles, and abnormal fixation of certain joints (contractures). A contracture occurs when thickening and shortening of tissue such as muscle fibers causes deformity and restricts movement of affected areas, especially the joints. Contractures of the ankles, knees, hips, and elbows may be seen. Without physical therapy treatment, leg braces may be needed by age 8-9 to assist affected individuals to walk. By approximately ages 10 to 12, most affected individuals require a wheelchair. As a result of scoliosis, pulmonary function may be impaired, which can lead to pulmonary compromise.

Children with Duchenne muscular dystrophy have reduced bone density and an increased risk of developing fractures of certain bones, such as hips and spine. Many affected individuals will display mild to moderate degrees of non-progressive intellectual impairment and learning disabilities.

By the late teens, Duchenne muscular dystrophy may also be characterized by additional potentially life-threatening complications including weakness and deterioration of the heart muscle (cardiomyopathy). Cardiomyopathy can result in impairment in the ability of the heart to pump blood, irregular heartbeats (arrhythmias), and heart failure. Another serious complication associated with Duchenne muscular dystrophy is weakness and deterioration of muscles in the rib cage. This can result in an increased susceptibility to respiratory infections (e.g., pneumonia), difficulty coughing, and, ultimately, respiratory failure.

Pharyngeal weakness can result in episodes of aspiration, nasal regurgitation of liquids, and a nasal quality of voice.

Involvement of muscles within the gastrointestinal tract may result in dysmotility, a condition in which the passage of food through the digestive tract usually because of slow and uncoordinated movements of the muscles of the digestive tract. Gastrointestinal dysmotility may result in constipation and diarrhea.

Incontinence of urine and stools due to urethral and anal sphincter weakness is uncommon and, if present, is a late manifestation.

One third of patients with Duchenne muscular dystrophy may have various degree of cognitive impairment including learning disability, attention deficit and autistic spectrum disorder.

Rarely, malignant hyperthermia after anesthesia may be a presenting sign.

Symptomatic female carriers may have an early onset and progressive muscular dystrophy.

Intellectual disability

Intellectual impairment is seen in all patients; however, only 20% to 30% of patients have an intelligence quotient (IQ) less than 70. The degree of impairment does not correlate with disease severity. Most patients have only a mild form of learning impairment and can function in a regular classroom. Epilepsy is more common than in the general population, and uncommonly, autism-like behavior has been described.

Duchenne muscular dystrophy associated cardiomyopathy

Symptoms of cardiomyopathy can develop in the early teens and are present in almost all patients in their twenties. Persistent tachycardia and heart failure, maybe presenting signs. In affected patients, dilated cardiomyopathy is characterized by extensive fibrosis of the posterobasal left the ventricular wall. As the disease progresses, fibrosis can spread to the lateral free wall of the left ventricle. With the involvement of the posterior papillary muscle, significant mitral regurgitation can occur. Inter and intraatrial conduction abnormalities, possibly involving the AV node, can be seen. Arrhythmias, particularly supraventricular arrhythmias, are also associated with the developing cardiomyopathy.

Physical exam shows pseudohypertrophy of the calf muscle and occasionally the quadriceps muscle. Shortening of the Achilles tendon may be noted, and the patient may have hyporeflexia or areflexia. Ankle reflexes are preserved till late in the disease unless contractures develop. Knee deep tendon reflexes are less brisk than the ankle and can be lost by age 6. The brachioradialis reflex is brisker than the biceps or triceps deep tendon reflexes. Typically, children are noted to use their arms to lift themselves from a seated position on the ground. This is known as Gowers sign.

Duchenne muscular dystrophy diagnosis

A diagnosis of Duchenne muscular dystrophy is made based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests including molecular genetic tests. If the genetic tests are not informative, surgical removal and microscopic examination (biopsy) of affected muscle tissue that may reveal characteristic changes to muscle fibers. Specialized blood tests (e.g. creatine kinase) that evaluate the presence and levels of certain proteins in muscle (immunohistochemistry) are also used ⁸⁾.

Molecular genetic tests involve the examination of deoxyribonucleic acid (DNA) to identify specific a genetic mutation including deletions, duplications or single point mutations. Samples of blood or muscles cells may be tested. These techniques can also be used to diagnosis Duchenne muscular dystrophy before birth (prenatally).

Blood tests may reveal elevated levels of the creatine kinase (CK), an enzyme that is found in abnormally high levels when muscle is damaged. The detection of elevated CK levels (usually in the thousands or ten thousands range) can confirm that muscle is damaged or inflamed, but cannot confirm a diagnosis of Duchenne muscular dystrophy.

In some cases, a specialized test can be performed on muscle biopsy samples that can determine the presence and levels of specific proteins within cells. Various techniques such as immunostaining, immunofluorescence or Western blot (immunoblot) can be used. These tests involve the use of certain antibodies that react to certain proteins such as dystrophin. Tissue samples from muscle biopsies are exposed to these antibodies and the results can determine whether a specific muscle protein is present in the cells and in what quantity or what size.

Serum creatine kinase

Serum creatine kinase (CK) measurements are elevated before the development of clinical symptoms and signs and may also be elevated in newborns. Levels peak by age two and can be more than 10 to 20 times above the upper limit of normal. As age and disease progress, serum creatine kinase levels decrease as fibrosis and fat progressively replace muscle. Other muscle enzymes, such as aldolase levels and AST levels, may also elevate.

Asymptomatic carriers may also have elevated creatine kinase levels. This is seen in about 80% of cases, and the highest levels are noted between ages 8 and 12.

Muscle biopsy

A muscle biopsy will demonstrate endomysial connective tissue proliferation, scattered degeneration, and regeneration of myofibers, muscle fiber necrosis with a mononuclear cell infiltrate, and replacement of muscle with adipose tissue and fat.

The muscled biopsied are the quadriceps femoris and the gastrocnemius.

Electromyography

Characteristic myopathic features can be seen; however, this is nonspecific. Motor and sensory nerve conduction velocities are normal, and denervation is not present.

Gene analysis

Patients with Duchenne muscular dystrophy demonstrate the complete or near-complete absence of dystrophin gene. Dystrophin immunoblotting can be used to predict the severity of the disease. In Duchenne muscular dystrophy, patients are found to have less than 5% of the normal quantity of dystrophin.

Polymerase chain reactions (PCR) can also be used and detect up to 98% of mutations. Multiplex ligation-dependent probe amplification (MPLA) is also used to identify duplications and deletions. Duplications can lead to in-frame or out of frame transcription products. Fluorescence in situ hybridization (FISH) is used less frequently but is useful to identify small point mutations.

Dystrophin immunocytochemistry can also be sued to detect cases not identifies by PCR.

Electrocardiogram (ECG)

Characteristic ECG changes are tall R waves in V1-V6 with an increased R/S ratio and deep Q waves in leads I,aVL, and V5-6. Conduction abnormalities with arrhythmias may be identified with telemetry. As mentioned previously, supraventricular arrhythmias are more common. Intra-atrial conduction abnormalities are more common than AV or infra-nodal defects in Duchenne muscular dystrophy.

Echocardiogram

Evidence of dilated cardiomyopathy is present in almost all patients by the end of their teens or in their 20s.

Duchenne muscular dystrophy treatment

No medical cure exists for Duchenne muscular dystrophy and the disease has a poor prognosis. Treatments are aimed at the specific symptoms present in each individual. Treatment options should include physical therapy and active and passive exercise to build muscle strength and prevent contractures. Surgery may be recommended in some patients to treat contractures or scoliosis. Braces may be used to prevent the development of contractures. The use of mechanical aids (e.g., canes, braces, and wheelchairs) may become necessary to aid walking (ambulation).

Corticosteroids are used as standard of care to treat individuals with Duchenne muscular dystrophy ⁹⁾. These drugs slow the progression of muscle weakness in affected individuals and delay the loss of ambulation by 2-3 years. Two common corticosteroid drugs used to treat individuals with Duchenne muscular dystrophy are prednisone and deflazacort (which is not available in the United States).

In 2016, Exondys 51 (eteplirsen) injection was FDA approved to treat Duchenne muscular dystrophy and is the first drug approved for this condition. Exondys 51 is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13 percent of the population with Duchenne muscular dystrophy. Exondys 51 is made by Sarepta Therapeutics.

In 2017, Emflaza (deflazacort) was FDA approved to treat patients age 5 years and older with Duchenne muscular dystrophy. Emflaza is marketed by PTC Therapeutics.

Glucocorticoid therapy

Glucocorticoid therapy decreases the rate of apoptosis of myotubes and can decelerate myofiber necrosis. Prednisone is used in patients four years and older in whom muscle function is declining or plateauing.

Prednisone is recommended at a dosage of (0.75 mg/kg per day or 10 mg/kg per week is given over two weekend days).

Deflazacort, an oxazoline derivative of prednisone, is sometimes preferred over prednisone as it has a better side effect profile and has an estimated dosage equivalency of 1:1.3 compared with prednisone. The recommended dosage is 0.9 mg/kg/day.

Studies have shown that glucocorticoid treatment is associated with improved pulmonary function, delayed development of scoliosis reduces incidence and progression of cardiomyopathy and overall improved mortality.

Cardiomyopathy

Treatment with angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers is recommended. Early studies suggest that early treatment with ACE inhibitors may slow progression of the disease and prevent the onset of heart failure.

Overt heart failure is treated with digoxins and diuretics as in other patients with cardiomyopathy.

Surveillance consists of a cardiology assessment with ECG and echocardiogram. This should be performed at the time of diagnosis or by the age of 6 years. Routine surveillance should be performed once every two years until the age of 10 and then yearly after that. If evidence of cardiomyopathy is present, surveillance every six months is indicated.

Pulmonary interventions

Pulmonary function must be tested prior to the exclusive use of a wheelchair. This should be repeated twice a year once the patient reaches 12 years of age, must use a wheelchair or vital capacity is found to be less than 80% of predicted.

Orthopedic interventions

Physiotherapy to prevent contractures is the mainstay of the orthopedic interventions. Based upon patient requirements, passive stretching exercises, plastic ankle-foot orthosis during sleep, long leg braces to assist in ambulation may be used. Surgery to release contractures may be required for advanced disease. Surgery to correct scoliosis may improve pulmonary function.

Nutrition

Patients are at risk for malnutrition, including obesity. Calcium and vitamin D should be supplemented to prevent osteoporosis secondary to chronic steroid use. DEXA scanning should be obtained at age three and then repeated yearly.

Exercise

Guidelines recommend all patients participate in a gentle exercise to avoid disuse atrophy. A combination of swimming pool and recreation-based exercises is recommended. Activity should be reduced if myoglobinuria is noted or significant muscle pain develops.

Novel therapies

Gene therapies include medications that bind RNA and skip over the defective codon. This produces a shorter but potentially functional protein. Eteplirsen us an exon 51 skipping antisense oligonucleotides medications used for this purpose. Eteplirsen has been approved by the FDA for this purpose.

Care at home

Modifications to your house may be needed over time to accommodate a wheelchair to help your child remain mobile and independent. Items that can improve your child’s comfort and independence include soft pressure care mattresses, ramps and modified taps. Your child’s physiotherapist or occupational therapist can advise you.

Exercise

Gentle exercise and participation in physical activity have both psychological and physical benefits for children with Duchenne muscular dystrophy. Exercise can slow muscle degeneration and help to strengthen your child.

In addition to exercises recommended by your child’s physiotherapist, activities like playing at the park, riding a bike, swimming or hydrotherapy help flexibility, muscle strength and confidence. An increase in strength can improve performance of daily activities such as stair climbing and walking, and also help postural muscles needed to keep the spine straight. Swimming can still be enjoyed after walking and riding are no longer possible.

Regular play and incidental exercise will help keep your child participating in activities with their friends at school. As they become less comfortable walking, a wheelchair or electric scooter may help them to continue to participate in social and sporting activities and maintain independence.

Other benefits of exercise for children with Duchenne muscular dystrophy include maintaining range of motion in joints, and preventing spinal curvature (scoliosis) and obesity.

It is important to avoid your child becoming over-exerted or exhausted, however, as this can worsen their muscle damage.

Duchenne muscular dystrophy life expectancy

Duchenne muscular dystrophy prognosis is typically poor. Muscle weakness may present initially with difficulty in ambulation but progressively advances to such an extent that affected patients are unable to carry out activities of daily living and must use wheelchairs. Patients are often wheelchair dependent by the age of 12 years. Death occurs as a result of respiratory muscle weakness or cardiac complications in the teens or 20s ¹⁰⁾. Other causes of death are pneumonia, aspiration, or airway obstruction.

What is craniosynostosis

Craniosynostosis is a birth defect of the skull characterized by the premature closure of one or more of the cranial sutures or fibrous joints between the bones of the skull (joints between the bone plates) before brain growth is complete ¹⁾. Closure of a single suture is most common. Normally the skull expands uniformly to accommodate the growth of the brain and most cranial sutures fuse when a person is 20-30 years of age, with the exception being the metopic suture fusing around 6 months to 2 years; premature closure of a single suture restricts the growth in that part of the skull and promotes growth in other parts of the skull where sutures remain open. This results in a misshapen skull but does not prevent the brain from expanding to a normal volume. However, when many sutures close prematurely, the skull cannot expand to accommodate the growing brain, which leads to increased pressure within the skull and impaired development of the brain. Theoretically, a person can suffer consequences of an early skull suture fusion no matter what age it fuses. However, doctors usually see the most severe consequences when the fusion happens early in life, often before birth.

Craniosynostosis usually involves fusion of a single cranial suture, but can involve more than one of the sutures in your baby’s skull (complex craniosynostosis). In rare cases, craniosynostosis is caused by certain genetic syndromes (syndromic craniosynostosis).

Types of craniosynostosis are:

• Sagittal synostosis (scaphocephaly) is the most common type. It affects the main suture on the very top of the head. The early closing forces the head to grow long and narrow, instead of wide. Babies with this type tend to have a broad forehead. It is more common in boys than girls.
• Frontal plagiocephaly is the next most common type. It affects the suture that runs from ear to ear on the top of the head. It is more common in girls.
• Metopic synostosis is a rare form that affects the suture close to the forehead. The child’s head shape may be described as trigonocephaly. It may range from mild to severe.

Craniosynostosis can be gene-linked or caused by metabolic diseases (such as rickets or vitamin D deficiency) or an overactive thyroid. Some cases are associated with other disorders such as microcephaly (abnormally small head) and hydrocephalus (excessive accumulation of cerebrospinal fluid in the brain). The first sign of craniosynostosis is an abnormally shaped skull. Other features can include signs of increased intracranial pressure, developmental delays, or impaired cognitive development, which are caused by constriction of the growing brain. Seizures and blindness may also occur.

Primary craniosynostosis affects individuals of all races and ethnicities and is usually present at birth. Most forms of primary craniosynostosis affect men and women in equal numbers (although males outnumber females 2:1 for sagittal synostosis). Primary craniosynostosis affects approximately 0.6 in 100,000 people in the general population. Overall, craniosynostosis affects approximately 1 in 2,000-2,500 people in the general population. Approximately 80-90 percent of individuals with primary craniosynostosis have isolated defects. The remaining cases of primary craniosynostosis occur as part of a larger syndrome. More than 150 different syndromes have been identified that are potentially associated with craniosynostosis.

In most cases of primary craniosynostosis, affected children usually have normal intelligence and do not have other abnormalities besides the skull malformation. However, when multiple sutures are affected, the skull may be unable to expand enough to accommodate the growing brain. If left untreated, this can cause increased pressure within the skull (intracranial pressure) and can potentially result in cognitive impairment or developmental delays. Increased pressure within the skull can also cause vomiting, headaches, and decreased appetite. In some rare cases, additional symptoms can develop including seizures, misalignment of the spine, or eye abnormalities.

Treatment for craniosynostosis generally consists of surgery to improve the symmetry and appearance of the head and to relieve pressure on the brain and the cranial nerves. For some children with less severe problems, cranial molds can reshape the skull to accommodate brain growth and improve the appearance of the head.

Although neurological damage can occur in severe cases, most children have normal cognitive development and achieve good cosmetic results after surgery. Early diagnosis and treatment are key.

Does the exact time a suture prematurely fuses affect my child?

Yes. Because of the rapid brain growth in the first two years of life, the brain really relies on the sutures to grow the skull during this period. So the earlier in pregnancy the suture fuses, the greater the restriction. Clinically, this is seen as a more severe change in the shape of the head with earlier fusions. For example, a patient with a sagittal suture fusion that occurs in the second trimester of pregnancy will have a much more “scaphocephalic” skull than a patient that has a fusion occur at 6 months after birth. The earlier fusion will have a more significant effect on head shape compared to a later fusion that may produce a relatively normal appearing skull. There is a correlation with the degree of deformity and the restriction in volume. Consequently, the more severe restriction leads to a more severe increase in pressure that the brain experiences. So it follows that the earlier the fusion, the more likely a patient is to experience abnormally increased intracranial pressure earlier in life. There is not a lot of longitudinal data demonstrating this primarily because most kids showing increased intracranial pressure are operated early in life. We do, however, see this trend clinically.

What are the concerns about a fused suture?

There are a couple of concerns associated with a fused skull suture. First and foremost, the skull is not growing adequately to afford sufficient volume and configuration of the endocranial cavity for the developing brain. Inadequate endocranial volume leads to an increase in pressure within the brain cavity. As the disproportion between endocranial volume and brain volume veers further away from normal, the fluid spaces around and within the brain become compressed, and eventually the brain tissue itself becomes compressed.

Since the brain depends on a large percentage of heart’s output (roughly 30%) to function properly, there is an important hydrostatic gradient between systemic blood pressure and intracranial pressure that is necessary to keep the brain functioning well. There is not an exact answer to the question of “what is normal intracranial pressure” because we have never been able to establish experimentally in what range the best functioning brains in the world exist compared to lower functioning brains. Experimental data suggests that a good estimation of “normal” pressure” is less than 15 mm Hg on average in patients with normal blood pressure. Brains that exist in a range below 15 mmHg seem to be happy and function at their best. We all know from everyday life that a certain activity, like lifting a heavy weight, may be associated with a full feeling in the head. This feeling is caused by obstructed blood flow from the brain back to the heart. The blood backs up in the brain temporarily and leads to transient high pressure. So periods of high pressure are clearly normal for much of what we do as humans. We don’t get too excited by these occasional activity related “high pressure spikes”. However, when a patient experiences a lot of these spikes or their pressure is consistently above 20 mm Hg or so, we start to become concerned.

Another concern of some parents, and less to others, is the shape of the head and its impact on how the child appears when compared to other children. Obviously, the degree of deformity and the value a family attributes to appearance have a great impact here. There are clearly cases of children with very late onset craniosynostosis that have very little change in their external appearance; patients with early, in-utero fusion often have a much more noticeable difference in their external appearance compared to other children. The value of appearance is a very personal consideration. It is important for each patient and family to feel free to express his or her own opinions on this issue. While never the sole concern in the context of craniosynostosis, a family’s opinion on this issue is always valid and important to understand when making decisions on whether or not to treat the disorder, especially surgically.

Craniosynostosis prognosis

How well a child does depends on:

• How many sutures are involved
• The child’s overall health

Children with this condition who have surgery do well in most cases, especially when the condition is not associated with a genetic syndrome.

Craniosynostosis possible complications

Craniosynostosis results in head deformity that can be severe and permanent if it is not corrected. Complications may include:

• Increased intracranial pressure
• Seizures
• Developmental delay
• Permanent head and facial deformity
• Poor self-esteem and social isolation

The risk of intracranial pressure from simple craniosynostosis is small, as long as the suture and head shape are fixed surgically. But babies with complex craniosynostosis (syndromic craniosynostosis), particularly those with an underlying syndrome, may develop increased pressure inside the skull if their skulls don’t expand enough to make room for their growing brains. If untreated, increased intracranial pressure can cause:

• Developmental delays
• Cognitive impairment
• No energy or interest (lethargy)
• Blindness
• Eye movement disorders
• Seizures
• Death, in rare instances

Normal newborn skull anatomy and physiology

It is important to have an understanding of skull anatomy and growth in order to understand craniosynostosis. An infant’s skull has 7 bone plates that relate to each other through specialized joints called “cranial sutures”. Sutures are made of tough, elastic fibrous tissue and separate the bones from one another. Sutures meet up (intersect) at two spots on the skull called fontanelles, which are better known as an infant’s “soft spots”. Although there are several major and minor sutures, the sutures that potentially have the most clinical significance are the singular metopic and sagittal sutures, as well as the paired (right and left) coronal and lambdoid sutures (see Figure 1). The seven bones of an infant’s skull normally do not fuse together until around age two or later. The sutures normally remain flexible until this point. In infants with primary craniosynostosis, the sutures abnormally stiffen or harden causing one or more of the bones of the skull to prematurely fuse together. This in turn, may lead to asymmetric skull growth.

Cranial sutures are very unique and specialized joints (syndesmosis joints). Their primary purpose is to grow bone in response to the rapidly developing brain within the protective skull compartment (cranial cavity or calvarium). The skull not only needs to be firm to protect the brain from accidental blows, but should also be expansile to accommodate its rapid growth. The brain doubles in volume in the first year of life and almost triples in volume by the age of three. The sutures of the skull allow for this important but almost contradictory balance of protection and growth.

Each cranial suture is designed to generate growth in the skull in a very specific area and configuration, ultimately reflecting the size and shape of the underlying brain structure. The overall bone development from cranial sutures occurs in a direction perpendicular to the long axis of the suture. Understanding these two facts, it makes sense that a fusion of each suture independently would cause a unique head shape.

The greatest increase in brain volume (brain growth) occurs from 0 to 14 months of age. The size of a child’s brain typically reaches 80% of adult size by the age of 2. The growth in head circumference after that age is more related to growth in the thickness of the skull and scalp but not actual brain growth. “Hat size” increases but not necessarily “brain size”.

The various cranial sutures close at different ages. The metopic suture closes earliest, around 6 months to 2 years. The rest of the sutures stay open into the 20’s and 30’s. The brain and fluid cavities of the brain do continue to grow in volume as you go into early adulthood, albeit not nearly as rapidly as the first couple years of life. Since the skull is much firmer (calcified or “rock-like”) and thicker, the skull needs the sutures to grow bone for any increase in volume.

Interestingly, there is a lot of variability here. Doctors have operated on adults in their 30’s for reasons unrelated to their skull sutures and have coincidentally found open metopic sutures. They have also seen young adults with closed coronal, lambdoid, and sagittal sutures, but with normal head shapes and often, no indication or symptoms of high pressure.

Scientists have learned that a cranial suture’s purpose is to grow bone to accommodate a growing brain, and that most brain growth occurs in the first two years of life. The brain reaches 85% of adult size by age 3 years (see Figure 2. Brain size vs. age diagram).

So it makes sense that the sutures are vitally important in the first two years of life. The earlier the fusion, the more severe the restriction in growth and, consequently, volume provided to the brain.

Figure 1. Normal skull of a newborn

Figure 2. Brain size versus age diagram

Craniosynostosis types

Craniosynostosis may be subdivided based upon the exact cranial sutures and skull bones involved. Most cases of primary craniosynostosis involve only one suture. Each subdivision results in a different characteristic pattern of skull development. The subdivisions of craniosynostosis include sagittal synostosis, coronal synostosis, metopic synostosis, and lambdoid synostosis. Synostosis is a medical term for the fusion of bones that are normally separate.

In rare cases, individuals with primary craniosynostosis have premature fusion of multiple sutures also known as complex craniosynostosis. A specific form of complex craniosynostosis involving multiple sutures is known as Kleeblattschadel (which is German for “cloverleaf” ) deformity. Fusion of multiple sutures causes the skull to appear flattened and divided into three lobes, thus resembling a cloverleaf. Most cases of complex craniosynostosis are linked to genetic syndromes and are called syndromic craniosynostosis. Kleeblattschadel deformity usually occurs as part of a syndrome.

Other reasons for a misshapen head

A misshapen head doesn’t always indicate craniosynostosis. For example, if the back of your baby’s head appears flattened, it could be the result of your baby spending too much time on one side of his or her head. This can be treated with regular position changes, or if significant, with helmet therapy (cranial orthosis) to help reshape the head to a more normal appearance.

Sagittal craniosynostosis

The most common form of craniosynostosis is sagittal synostosis (hardening of the sagittal suture). The sagittal suture is the joint that runs from the front to the back of the skull and that separates the two bones that form the sides of the skull (parietal bones). Premature closure of this suture results in an abnormally long, narrow head (scaphocephaly) due to the restricted sideways growth (width) of the skull.

Coronal craniosynostosis

Coronal synostosis refers to the premature closure of one of the coronal sutures, which are the joints that separate the two frontal bones from the two parietal bones. The coronal sutures extend across the skull, almost from one ear to the other. The two coronal sutures meet at the “soft spot” (anterior fontanelle) located toward the front and of the skull.

Premature fusion of one of the coronal sutures (unicoronal) that run from each ear to the top of the skull may cause your baby’s forehead to flatten on the affected side and bulge on the unaffected side. It also leads to turning of the nose and elevation of the eye socket on the affected side. The skull may appear twisted or lopsided and the forehead and orbit of the eye may appear flattened on one side whereas the opposite side of the forehead may appear to bulge as part of the brain’s unrestricted growth on this side. This specific skull shape is sometimes referred to as frontal plagiocephaly.

When both of the coronal sutures fuse prematurely (bicoronal), it causes the skull to appear abnormally short and disproportionally wide (brachycephaly), it gives your baby’s head a short and wide appearance, most commonly with the forehead tilted forward.

Metopic craniosynostosis

Metopic synostosis refers to the premature fusion of the metopic suture, which is the joint that separates the two frontal bones of the skull. It runs from the top of the forehead to the anterior fontanelle (frontal soft spot). This condition causes a keel-shaped forehead and eyes that are set closer together than normal (hypotelorism). When viewed from above the skull may appear to be shaped triangularly, a condition referred to as trigonocephaly. A ridge may be apparent running down the middle of the forehead, which may appear narrow. The soft spot found toward the back of the skull (anterior fontanelle) is usually absent or prematurely closed. The presence of a metopic ridge (a palpable/ visible prominence over the midline of the forehead) is relatively common and not all individuals with this ridge have trigonocephaly.

Lambdoid craniosynostosis

Lambdoid synostosis, also known as posterior plagiocephaly, is the premature fusion of the lambdoid suture, which is the joint that separates the bone that forms the lower back of the skull (occipital bone) from the parietal bones. One side of the rear of the head may appear flatter than the other when viewed from above. The ear on the affected side may be pulled backward and stick out farther than the other ear. A small bump may also be present behind the ear on the affected side. Whereas true lambdoid synostosis is extremely rare (1/200,000), this should not be confused with the nearly ubiquitous lambdoid positional plagiocephaly. Fortunately, there are physical features that help to differentiate these two conditions and children with positional plagiocephaly usually have compensatory overgrowth at the forehead on the same side.

Figure 3. Types of craniosynostosis skull deformity (the following diagrams and clinical pictures demonstrate the unique forms that occur with each suture fusion)

Craniosynostosis symptoms

The signs of craniosynostosis are usually noticeable at birth, but they’ll become more apparent during the first few months of your baby’s life.

Symptoms depend on the type of craniosynostosis. They may include:

• No “soft spot” (fontanelle) on the newborn’s skull
• Development of a raised, hard ridge along affected sutures
• Unusual head shape or a misshapen skull, with the shape depending on which of the sutures are affected
• An abnormal feeling or disappearing fontanel on your baby’s skull
• Slow or no increase in the head size over time as the baby grows

Often the most obvious sign of craniosynostosis is a unique head shape and orbital asymmetry, although craniosynostosis is not the only cause of a unique head shape. Our team has strong experience in evaluating unique head shapes, determining the cause of each one, and deciphering out other causes from craniosynostosis.

In addition to a unique head shape, the signs and symptoms of elevated intracranial pressure may or may not be present. The most consistent symptom of elevated pressure is the presence of chronic, recurrent headaches. Because there are many different causes of headaches, it is important to distinguish between the patterns of headaches caused by increased intracranial pressure and those that are caused by other reasons. Again, multidisciplinary experience plays an important role in this.

Prolonged elevated pressure and very high pressure cause irreversible damage to the optic nerves (nerves that are key to vision). Sometimes this damage can be found by examination of the retina by a pediatric ophthalmologist (a medical doctor of the eyes). The physical exam finding is called papilledema. Once papilledema is seen on exam, it is an indication that the nerve has suffered a permanent injury that results in worsening vision for the patient.

There is some data to suggest that long-standing or early-onset pressure elevation on the brain can lead to a brain that functions at a lower level than it would have if it never experienced elevated pressure. Longitudinal studies regarding IQ and brain function in children are very difficult to carry out, and comparing these children to unaffected cohorts is riddled with issues that can challenge the validation of these studies. Clinically, children who are experiencing very high pressure from other conditions, like hydrocephalus, do not function very well. Pressure can get so high in some of these cases that it can become life threatening. While most children with craniosynostosis do not experience pressure as high as hydrocephalus, we do see similar pressure effects on some patients with the higher end of the pressure spectrum. The effects of long standing, low-grade pressure are much less clear, for sure.

Lastly, there are a number of radiographic signs that the team looks for on imaging studies. No one sign indicates high pressure, but the presence of several of them together usually supports a presumptive diagnosis of elevated intracranial pressure. A “copper-beaten” pattern to the inner cranial surface, loss of extra-axial fluid spaces, narrowing of the ventricles, effacement of the sulci, and blunting of cerebral gyri all indicate some degree of cephalo-cranial disproportion or, simply, a mismatch between the size of the brain and the volume provided to it by the skull.

Related disorders

Symptoms of the following disorders can be similar to those of primary craniosynostosis. Comparisons may be useful for a differential diagnosis.

Secondary craniosynostosis refers to the development of an abnormal skull shape due to the premature closure of the cranial sutures that occurs because of a primary failure of brain growth. Proper brain growth pushes the bones of the skull apart, a normal process to allow the skull to accommodate the growing brain. Failure of proper brain growth allows the bones to fuse together prematurely. A variety of different underlying causes can result in the failure of brain growth and subsequent craniosynostosis. These causes include metabolic disorders, certain blood (hematological) disorders, malformation disorders, and the exposure of the fetus to certain drugs including valproic acid or phenytoin. Secondary craniosynostosis is usually associated with additional symptoms including facial abnormalities, developmental delays and microcephaly, a condition in which the head circumference is smaller than would be expected for an infant’s age and sex.

Deformational (positional) plagiocephaly, sometimes known as positional plagiocephaly, is a condition in which the skull becomes misshapen due to repeated or constant pressure on a specific area of the skull. Deformational (positional) plagiocephaly is not associated with premature fusion of cranial sutures. It is caused by external forces acting on an infant’s skull. It can develop before birth or after birth. The incidence of deformational (positional) plagiocephaly has increased since the American Academy of Pediatrics recommended that newborns sleep on their backs to prevent sudden infant death syndrome. This repetitive sleeping pattern results in the flattening of the back of the infant’s head or often preceded by the presence of torticollis at birth. Deformational plagiocephaly is not associated with any other abnormalities and does not affect a child’s development.

Craniosynostosis causes

The exact cause of primary (isolated) craniosynostosis is unknown. Genes may play a role, but there is usually no family history of the condition. More often, it may be caused by external pressure on a baby’s head before birth.

• Nonsyndromic craniosynostosis is the most common type of craniosynostosis, and its cause is unknown, although it’s thought to be a combination of genes and environmental factors.
• Syndromic craniosynostosis is caused by certain genetic syndromes, such as Apert syndrome, Pfeiffer syndrome or Crouzon syndrome, which can affect your baby’s skull development.

Primary isolated craniosynostosis refers to cases that are not associated with a larger syndrome. Most cases occur randomly for no apparent reason (sporadically) although an infant’s position in utero, large size and presence of twins have all been implicated as etiological factors. A variety of different genetic and environmental factors are suspected to play a role in the development of primary isolated craniosynostosis.

In extremely rare cases, primary isolated craniosynostosis is genetic and in such cases is usually inherited as an autosomal dominant trait. Most cases of primary craniosynostosis that occur as part of a syndrome are also inherited as autosomal dominant traits. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

The most widely accepted theory for the development of primary craniosynostosis is a primary defect in the ossification (hardening) of the cranial bones. The underlying cause of this defect is unknown in primary isolated craniosynostosis. In the syndromic forms, the defect is due to a mutation in a specific gene. Syndromic forms of primary craniosynostosis include Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome and Saethre-Chotzen syndrome.

However, most children with craniosynostosis are otherwise healthy and have normal intelligence.

Craniosynostosis diagnosis

Craniosynostosis requires evaluation by specialists, such as a pediatric neurosurgeon or plastic surgeon.

Diagnosis of craniosynostosis may include:

• Physical exam. Your doctor will feel your baby’s head for abnormalities such as suture ridges, and look for facial deformities.
• Imaging studies. A computerized tomography (CT) scan of your baby’s skull can show whether any sutures have fused. Fused sutures are identifiable by their absence, because they’re invisible once fused, or by the ridging of the suture line. A laser scan and photographs also may be used to make precise measurements of the skull shape.
• Genetic testing. If your doctor suspects an underlying genetic syndrome, genetic testing may help identify the syndrome.

A diagnosis of primary craniosynostosis is made based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation that includes careful assessment of the shape of the skull. A variety of specialized tests include specialized imaging techniques. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI), although a head CT is best for evaluating suture / bone involvement. Although there has been recent debate about the need for CT’s prior to surgery (and accompanying radiation), there are a number of literature reports documenting their value in ruling out other suture involvement as well as brain abnormalities. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. Routine skull x-rays have been discontinued as a routine diagnostic tool in the setting of craniosynostosis due to the lack of sensitivity and frequent inaccuracy.

In some cases, a diagnosis of primary craniosynostosis may be made before birth (prenatally) by ultrasound examination. During an ultrasound, reflected sound waves create an image of the developing fetus. An increasing number of children are also being diagnosed via prenatal MRI.

Craniosynostosis treatment

The treatment of primary craniosynostosis is directed toward the specific symptoms that are apparent in each individual. In general, it is an issue of appearance versus intracranial pressure. Mild cases of craniosynostosis may not need treatment. Your doctor may recommend a specially molded helmet to help reshape your baby’s head if the cranial sutures are open and the head shape is abnormal. In this situation, the molded helmet can assist your baby’s brain growth and correct the shape of the skull.

Surgery is the main form of therapy for affected children, but not all children will require surgery. Surgery is performed to create and ensure that there is enough room within the skull for the developing brain to grow; to relieve intracranial pressure (if present); and to improve the appearance of an affected child’s head. The various surgical approaches (endoscopic, Pi procedures, total calvarial reconfiguration, springs, distraction, etc) each have their unique advantages / disadvantages and are best discussed in detail with the treating physician at the time of evaluation.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Craniosynostosis surgery

Currently, the only effective treatment for craniosynostosis is surgery. The type and timing of surgery depends on the type of craniosynostosis and whether there’s an underlying genetic syndrome.

The purpose of surgery is to correct the abnormal head shape, reduce or prevent pressure on the brain, create room for the brain to grow normally and improve your baby’s appearance. This involves a process of planning and surgery.

There are three goals of craniosynostosis surgery:

1. Expand the intracranial volume sufficiently for the brain to avoid high pressure, including the immediate need for more volume and anticipating the future need for brain growth
2. Reconstruct the skull into a normal form and appearance
3. Provide an intact skull that is protective of the brain for unrestrictive activity

Surgical planning

Imaging studies can help surgeons develop a surgical procedure plan. Virtual surgical planning for treatment of craniosynostosis uses high-definition 3-D CT scans of your baby’s skull to construct a computer-simulated, individualized surgical plan. Based on that virtual surgical plan, customized templates are constructed to guide the procedure.

Craniosynostosis surgery

A team that includes a specialist in surgery of the head and face (craniofacial surgeon) and a specialist in brain surgery (neurosurgeon) generally performs the procedure. Surgery can be done by endoscopic or open surgery. Both types of procedures generally produce very good cosmetic results with low risk of complications.

• Endoscopic surgery. This minimally invasive surgery may be considered for babies up to age 6 months who have single-suture craniosynostosis. Using a lighted tube and camera (endoscope) inserted through small scalp incisions, the surgeon opens the affected suture to enable your baby’s brain to grow normally. Compared with an open procedure, endoscopic surgery has a smaller incision, typically involves only a one-night hospital stay and usually does not require a blood transfusion.
• Open surgery. Generally, for babies older than 6 months, open surgery is done. The surgeon makes an incision in the scalp and cranial bones, then reshapes the affected portion of the skull. The skull position is held in place with plates and screws that are absorbable. Open surgery typically involves a three- or four-day hospital stay, and blood transfusion is usually necessary. It’s generally a one-time procedure, but in complex cases, multiple open surgeries are often required to correct the baby’s head shape.

After endoscopic surgery, visits at certain intervals are required to fit a series of helmets to help shape your baby’s skull. If open surgery is done, no helmet is needed afterward.

Craniosynostosis surgical procedure

This surgery is done in the operating room under general anesthesia. This means your child will be asleep and will not feel pain.

Traditional surgery is called open repair. It includes these steps:

• The most common place for a surgical cut to be made is over the top of the head, from just above one ear to just above the other ear. The cut is usually wavy. Where the cut is made depends on the specific problem.
• A flap of skin, tissue, and muscle below the skin, and the tissue covering the bone are loosened and raised up so the surgeon can see the bone.
• A strip of bone is usually removed where two sutures connect. This is called a strip craniectomy. Sometimes, larger pieces of bone must also be removed. This is called synostectomy. Parts of these bones may be changed or reshaped when they are removed. Then, they are put back. Other times, they are not.
• Sometimes, bones that are left in place need to be shifted or moved.
• Sometimes, the bones around the eyes are cut and reshaped.
• Bones are fastened using a plate with screws that go into the skull. More and more surgeons are using resorbable plates and screws. The plates may expand as the skull grows.

Surgery usually takes 3 to 7 hours. Your child will probably need to have a blood transfusion during or after surgery to replace blood that is lost during the surgery.

A newer kind of surgery (endoscopic surgery) is used for some children. This type is usually done for children younger than 3 to 6 months old.

• The surgeon makes one or two small cuts in the scalp. Most times these cuts are each just 1 inch (2.5 centimeters) long. These cuts are made above the area where the bone needs to be removed.
• A tube (endoscope) is passed through the small cuts. The scope allows the surgeon to view the area being operated on. Special medical devices and a camera are passed through the endoscope. Using these devices, the surgeon removes some bone through the cuts.
• This surgery usually takes about 1 hour. There is much less blood loss with this kind of surgery.
• Most children need to wear a special helmet to protect their head for a period of time after surgery.

Children do best when they have this surgery when they are 3 months old. The surgery should be done before the child is 6 months old.

Craniosynostosis surgery risks

Risks for any surgery are:

• Breathing problems
• Infection, including in the lungs and urinary tract
• Blood loss (children having an open repair may need a transfusion)
• Reaction to medicines

Risks for craniosynostosis surgery are:

• Infection in the brain
• Bones connect together again, and more surgery is needed
• Brain swelling
• Damage to brain tissue

After the craniosynostosis surgical procedure

After surgery, your child will be taken to an intensive care unit (ICU). Your child will be moved to a regular hospital room after a day or two. Your child will stay in the hospital for 3 to 7 days.

• Your child will have a large bandage wrapped around the head. There will also be a tube going into a vein. This is called an IV.
• The nurses will watch your child closely.
• Tests will be done to see if your child lost too much blood during surgery. A blood transfusion will be given, if needed.
• Your child will have swelling and bruising around the eyes and face. Sometimes, the eyes may be swollen shut. This often gets worse in the first 3 days after surgery. It should be better by day 7.
• Your child should stay in bed for the first few days. The head of your child’s bed will be raised. This helps keep the swelling down.

Talking, singing, playing music, and telling stories may help soothe your child. Acetaminophen (Tylenol) is used for pain. Your doctor can prescribe other pain medicines if your child needs them.

Most children who have endoscopic surgery can go home after staying in the hospital one night.

Follow instructions on caring for your child at home.

What to expect at home

Swelling and bruising on your baby’s head will get better after 7 days. But swelling around the eyes may come and go for up to 3 weeks.

Your baby’s sleeping patterns may be different after getting home from the hospital. Your baby may be awake at night and sleep during the day. This should go away as your baby gets used to being at home.

Self-care

Your baby’s surgeon may prescribe a special helmet to be worn, starting 3 weeks after the surgery. This helmet has to be worn to help further correct the shape of your baby’s head.

• The helmet needs to be worn every day for the first year after surgery.
• It has to be worn at least 23 hours a day. It can be removed during bathing.
• Even if your child is sleeping or playing, the helmet needs to be worn.

Your child should not go to school or daycare for at least 2 to 3 weeks after the surgery.

You’ll be taught how to measure your child’s head size. You should do this each week as instructed.

Your child will be able to return to normal activities and diet. Make sure your child doesn’t bump or hurt the head in any way. If your child is crawling, you may want to keep coffee tables and furniture with sharp edges out of the way until your child recovers.

If your child is younger than 1, ask the surgeon if you should raise your child’s head on a pillow during sleeping to prevent swelling around the face. Try to get your child to sleep on the back.

Swelling from the surgery should go away in about 3 weeks.

To help control your child’s pain, use children’s acetaminophen (Tylenol) as your child’s doctor advises.

Wound care

Keep your child’s surgery wound clean and dry until the doctor says you can wash it. DO NOT use any lotions, gels, or cream to rinse your child’s head until the skin has completely healed. DO NOT soak the wound in water until it heals.

When you clean the wound, make sure you:

• Wash your hands before you start.
• Use a clean, soft washcloth.
• Dampen the washcloth and use antibacterial soap.
• Clean in a gentle circular motion. Go from one end of the wound to the other.
• Rinse the washcloth well to remove the soap. Then repeat the cleaning motion to rinse the wound.
• Gently pat the wound dry with a clean, dry towel or a washcloth.
• Use a small amount of ointment on the wound as recommended by the child’s doctor.
• Wash your hands when you finish.

When to call your doctor

Call your child’s doctor if your child:

• Has a temperature of 101.5ºF (40.5ºC)
• Is vomiting and cannot keep food down
• Is more fussy or sleepy
• Seems confused
• Seems to have a headache
• Has a head injury

Also call if the surgery wound:

• Has pus, blood, or any other drainage coming from it
• Is red, swollen, warm, or more painful

CLOVES syndrome

CLOVES syndrome which stands for Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal/Skeletal Anomalies and/or Scoliosis, is a rare condition that is primarily characterized by congenital overgrowth of fatty tissue; malformations of the vascular system (the vessels that carry blood and lymph throughout the body); epidermal nevi; and spinal or skeletal abnormalities ¹⁾. Other signs and symptoms may include disproportionate fat distribution, overgrowth of the extremities (arms and legs), skin abnormalities and kidney problems such as an unusually small or absent kidney ²⁾. The severity of CLOVES syndrome and the associated signs and symptoms vary significantly from person to person.

CLOVES syndrome is rare and evident at birth. It affects males and females equally regardless of their race or ethnicity. Many of the patients with CLOVES syndrome are misdiagnosed as having other syndromes such as Klippel-Trenaunay syndrome or Proteus syndrome.

CLOVES syndrome is caused by somatic mutations in the PIK3CA gene ³⁾. Because these mutations do not affect egg or sperm cells, CLOVES syndrome is not passed on from parent to child.

Given its rarity and complexity, patients with CLOVES syndrome should be referred to a specialized center with experience in managing complex overgrowth and vascular anomalies for confirmation of diagnosis, interdisciplinary assessment, delineation of clinical risks and complications, management and coordination of care ⁴⁾. Treatment is based on the signs and symptoms present in each person ⁵⁾.

Treatment for CLOVES syndrome involves addressing each symptom or complication and improving quality of life (palliative care). There is currently no cure. Palliative care aims to relieve symptoms caused by masses and minimize disease progression and disability. Management is very individualized because symptoms can vary in severity and body location for each person. Follow-up with various specialists is recommended every 6 months until the end of puberty, to assess for overgrowth and complications ⁶⁾.

Medical treatment may include embolization and surgical removal of masses, especially those that are large, deep, or in the spinal region ⁷⁾. Sclerotherapy may be used in adults to lessen pain and reduce the size of vascular and lymphatic malformations ⁸⁾.

Orthopedic and neurosurgical checkups with possible surgical intervention are needed to reduce complications from overgrowth. Surveillance of hands, feet, and limb abnormalities is important so surgery can be done promptly to minimize limb disfigurement and loss of function. Because there is increased risk of tumor growth in people with overgrowth syndromes, people with CLOVES syndrome should have surveillance for tumors and have masses assessed ⁹⁾.

In general, the earlier surveillance and intervention are started, the better the outcome ¹⁰⁾.

Is there a cure for CLOVES syndrome?

There is no cure for CLOVES syndrome, but experienced vascular anomaly specialists can manage or prevent symptoms with the right medical and surgical care. Treatment for CLOVES syndrome involves addressing each symptom or complication and improving quality of life (palliative care). Surgery and other medical interventions are the only treatments for CLOVES syndrome overgrowth, vascular anomalies and other related medical issues.

CLOVES syndrome causes

CLOVES syndrome is a nonhereditary disorder caused by a somatic (body cell) mutation in a gene known as PIK3CA. Mutations in this growth regulatory PIK3CA gene result in two sets of cells within the body (mosaic status): those with the mutation and those without the mutation. The mutated cells give rise to the abnormal tissue.

The PIK3CA gene provides instructions for making the p110 alpha (p110α) protein, which is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K). The p110α protein is called the catalytic subunit because it performs the action of PI3K, while the other subunit (produced by a different gene) regulates the enzyme’s activity.

Like other kinases, PI3K adds a cluster of oxygen and phosphorus atoms (a phosphate group) to other proteins through a process called phosphorylation. PI3K phosphorylates certain signaling molecules, which triggers a series of additional reactions that transmit chemical signals within cells. PI3K signaling is important for many cell activities, including cell growth and division (proliferation), movement (migration) of cells, production of new proteins, transport of materials within cells, and cell survival. Studies suggest that PI3K signaling may be involved in the regulation of several hormones and may play a role in the maturation of fat cells (adipocytes).

CLOVES syndrome symptoms

CLOVES syndrome belongs to the spectrum of overgrowth syndromes with complex vascular anomalies caused by mosaic mutations in the PIK3CA gene. The rare CS may affect the soft tissue, blood vessels, bone and internal organs. The manifestations are very variable ranging from mild to severe anomalies. These abnormalities are typically present at birth.

The most common features of CLOVES syndrome are:

1. Fatty overgrowth. Soft fatty masses of variable size are noted at birth and can be located in the back, flanks, axilla, abdomen and buttocks. These masses may affect one or both sides of the body. The skin over the mass is typically covered with a red-pinkish birthmark (capillary malformation or port-wine stain).
2. Vascular anomalies. Dilated veins in the chest, upper and lower extremities may cause clot formation and occasionally serious pulmonary embolism (clot travelling from the vein to the lungs). Lymphatic malformations are abnormal, large spaces filled with lymph. These malformations are frequently noted within the fatty masses or in the abdomen, chest and extremities. A small subgroup of patients may suffer from the more aggressive arteriovenous malformation around the area of the spinal cord.
3. Abnormal extremities (arms and legs) are common. Large wide hands or feet, large fingers or toes, wide space between digits (sandal gap toe) and uneven size of extremities are common.
4. Spinal anomalies include scoliosis (curving of the spine), fatty masses and vessels pushing on the spinal cord and tethered cord (spinal cord fixed by abnormal band).
5. Skin birthmarks include port-wine stains, prominent veins, lymphatic vesicles, moles and epidermal nevus (slightly raised areas of skin with light brownish color).
6. Kidney anomalies. The size of the kidneys could be asymmetric (one is larger) and may show some abnormal features on imaging studies. Wilms tumor has been noted in a small number of young patients with CLOVES syndrome. This requires screening with serial ultrasound examinations during childhood.

Additional findings can occur in CLOVES syndrome including bleeding from the intestine, urinary bladder and asymmetric face and head.

Not all patients with CLOVES syndrome have all these signs, but rather a combination of abnormalities. Some can be subtle and a dedicated physical exam and proper imaging studies are required.

CLOVES syndrome diagnosis

Because symptoms of CLOVES syndrome can be subtle or obvious, it’s critical to seek a diagnosis from an experienced vascular anomalies specialist. CLOVES is still not widely known and so rare that an ultrasound is not a foolproof way to detect it. A clinical exam must be performed after birth. The diagnosis is evident at birth based on physical signs and symptoms. Prenatal diagnosis with imaging tools is feasible.

To diagnose CLOVES syndrome, doctors will usually combine these steps:

• obtain a detailed medical and family history
• perform a thorough physical exam
• order imaging studies such as magnetic resonance imaging (MRI), computed tomography (CT) scans, ultrasound and x-rays

Confirmation of diagnosis can be done with molecular genetic testing for the PIK3CA gene mutation. Imaging studies include plain x-rays (radiography), magnetic resonance imaging (MRI) of the chest, abdomen, pelvis, spine and limbs and ultrasound for vascular anomalies and kidneys.

Children with CLOVES syndrome are often mistakenly diagnosed as having other disorders that cause overgrowth of the blood vessels and abnormalities in certain parts of the body, such as:

• Hemihypertrophy: a condition in which the structures on one side of a child’s body are larger than on the other
• Klippel-Trenaunay syndrome: a rare disease that causes abnormal fatty growths of the leg, dilated veins, lymphatic malformations and port-wine stain birthmarks
• Proteus syndrome: a rare condition that causes progressive deformities of the bone, skin and soft tissue

The main difference between these conditions and CLOVES syndrome is that CLOVES syndrome causes a combination of vascular, skin and limb/torso abnormalities and truncal/spinal abnormalities (like fatty masses, scoliosis or tethered cord).

Early MRI

CLOVES syndrome patients may benefit from an MRI of the chest, abdomen, pelvis and lower extremities performed in the neonatal or early infantile period or at the time of initial presentation. This help define deeper components of the syndrome that may require from intervention in early childhood (e.g. lymphatic and venous malformations, gastrointestinal and genitourinary involvement); as well as characterize overgrowth and extension into the retroperitoneum, peritoneum, superior and posterior mediastinum, pelvis, pleural spaces and paraspinal muscles, tethered spinal cord, neural tube defects).

If the study (referred to as “early MRI”) requires general anesthesia, the scan can be delayed until the risk of anesthesia is reduced (i.e. > 6 months of age). Optimal timing of imaging best balances the risks of anesthesia with the information to be gained.

Genetics

CLOVES syndrome is diagnosed primarily on the basis of clinical and imaging findings. Discovery of the somatic mutation in PIK3CA gene in resected tissues from patients with CLOVES syndrome opens up the possibility of a medical therapy; PI3K and mTOR inhibitors are actively being investigated. Currently there are no commercially available genetic tests for detecting PIK3CA mutations. At the research level, droplet digital polymerase chain reaction (PCR) can reliably detect the most common mutations. A positive test can confirm the mutation, whereas a negative test result cannot exclude the mutation. The presence or absence of the mutation does not define a patient as having CLOVES syndrome.

CLOVES syndrome treatment

The management of CLOVES syndrome can be very challenging and requires an interdisciplinary team of physicians with experience in overgrowth and vascular anomalies. The treatment should address the specific problems in the affected child.

Some of the treatments your child’s care team might recommend include:

• Drug therapy with sirolimus: Also known as rapamycin, this oral medication suppresses the immune system and slows the growth of abnormal lymphatic vessels that cause the vascular anomalies present in children with CLOVES. It can also improve symptoms, including pain.
• Sclerotherapy: This non-surgical procedure can help reduce the size of the vascular anomalies associated with CLOVES, as well as the pain they may cause.
• Embolization: This minimally invasive procedure is used to reduce the size of arteriovenous malformations and other vascular anomalies associated with CLOVES syndrome.
• Debulking surgery: Some children need debulking surgery to remove a portion of the overgrown tissue and blood vessels caused by CLOVES syndrome. Though debulking is a major, invasive operation, it can be life-changing for children who have limited mobility due to limb abnormalities or painfully overgrown veins.
• IVC Filter: A device called an inferior vena cava (IVC) filter can prevent pulmonary embolisms, life-threatening clots that can form and travel through the bloodstream and into the lungs of children with CLOVES. The filter, which is surgically implanted, sits in the inferior vena cava (the main abdominal vein responsible for transporting blood from a child’s lower body) and traps any clots, before they reach the heart and lungs.

Orthopedic procedures are usually necessary for large limb anomalies. CLOVES syndrome patients may benefit from hematology evaluation including basic coagulopathy work up early in life and pre-procedurally. Large veins and lymphatic malformations should be treated with minimally invasive procedures such as sclerotherapy, embolization and laser treatment before undergoing surgical procedures due to the risk of vein thrombosis. Tethered cord is treated surgically.

Medical therapy with sirolimus demonstrated promising results; particularly for patients with lymphatic malformation and pain. The use of sirolimus or other medical therapies is rapidly changing in CLOVES syndrome and other vascular anomalies and should be guided by an experienced hematologist/oncologist.

Nutritional support

CLOVES syndrome patients with poor weight gain or failure to thrive may benefit from nutritional consultation and ongoing support. The presence of both fatty overgrowth in some areas and the appearance of malnourishment are frequent in CLOVES syndrome and not currently well understood. Many patients have improved weight gain in later childhood and some may improve after resection of large lipomatous masses.

Psychosocial support

Comprehensive interdisciplinary management should address the psychological burden of the disease on the child and issues related to adaptation, coping, and distress. Management should aim at alleviating not only the physical issues, but also the psychological burden on the child and the family. Stress factors among caregivers should be identified so proper intervention or support can be provided. Social workers help families with coping with a diagnosis, mental health, parenting and behavioral concerns as well as identifying helpful resources. Psychosocial intervention can also be provided through community-based organizations or support groups.

Lymphatic malformation

Lymphatic malformations in CLOVES syndrome vary in size from small skin vesicles of minor clinical significance to massive, deforming lesions, which are typically associated with fatty overgrowth. Lymphatic malformations may be macrocystic, microcystic or combined. The clinical consequences and treatment of these lesions vary widely. Small, superficial cutaneous vesicles are prone to leakage, bleeding, and increase the risk of infection. Larger lymphatic malformations, typically associated with overgrowth, are most commonly located in the chest and abdominal wall with variable extension into the abdominal and thoracic cavities. The morbidity of these lesions is related to mass effect (resulting in decreased range of motion and deformity) and infection.

Macrocystic lymphatic malformations can be treated with minimally-invasive techniques such as sclerotherapy. Large lymphatic malformations associated with overgrowth may benefit from surgical debulking. A combined approach with sclerotherapy and resection can be beneficial in selected patients.

When lymphatic malformations become infected, prompt evaluation and oral antibiotic treatment are necessary. Some patients may initially require intravenous antibiotics. Patients typically require a long course of at least 14 to 21 days of treatment. For recurrent infections, a prolonged course of prophylactic antibiotics should be considered. Infected lymphatic macrocysts may require drainage and sclerotherapy. Proper hygiene is imperative for cutaneous and mucosal lymphatic vesicles; they can be treated with sclerotherapy (including the use of bleomycin) or CO2 laser photovaporation.

For patients with significant complications from the lymphatic components of their disease, medical therapy with sirolimus has been used with promising early results. The use of sirolimus or other medical therapies is rapidly changing in CLOVES syndrome and other vascular anomalies and should be guided by an experienced hematologist/oncologist.

Venous malformation

Venous malformation also known as phlebectasia or dilatation of veins, in CLOVES syndrome is often seen in the upper and lower extremity and lateral truncal wall. These veins include orthotopic (normally located) or persistent embryonic veins. Involved orthotopic veins include the subclavian, axillary, innominate, intercostal, azygous, hemiazygous, short saphenous and jugular veins, as well as the superior vena cava (SVC) and inferior vena cava (IVC). Embryonic veins include the sciatic and marginal veins in the lower extremity and the lateral chest wall. Other anomalies, such as azygos continuation of the inferior vena cava, or persistent left superior vena cava, may exist. Ectatic veins can be the source of blood clot formation and life-threatening pulmonary embolism (thromboembolism). In addition, patients may develop painful clots (thrombophlebitis).

All patients should undergo preoperative imaging to assess the venous system. If an MRI has not been performed, proper imaging to evaluate the venous anatomy prior to any invasive intervention is strongly recommended.

Ultrasonography may demonstrate certain veins including subclavian, axillary, short saphenous and marginal veins in the lower extremity and the lateral truncal wall. Deeply seated veins (innominate, azygous, hemiazygous and sciatic veins as well as the superior vena cava (SVC) and inferior vena cava (IVC) can be visualized by MRI or CT.

Patients with an extensive venous malformation may have altered blood tests due to stagnant or slowed blood flow and increased activation of the clotting cascade as an indicator of blood clot formation with venous malformations.

• Thrombophlebitis can be treated with limb elevation, non-narcotic analgesics, and anti-inflammatory medications.
• Prior to invasive surgical procedures, CLOVES syndrome patients may benefit from evaluation by an anesthesiologist and multidisciplinary optimization of physical status.
• CLOVES syndrome patients with dilated veins and increased risk of venous thrombosis may benefit from prophylactic anticoagulation during the perioperative period. A hematology consultation and a coagulation profile should be obtained before any procedure. Anticoagulation is often recommended both pre- and post-procedure to minimize the risk of blood clot formation and migration to the lungs. Placement of temporary IVC (or SVC) filters may also be considered.
• Closure of the dilated veins may reduce the risk of thromboembolism, particularly prior to surgical procedures. Experts recommend closing specific dilated veins (lower limb and truncal marginal veins, axillary-subclavian, sciatic and short saphenous veins) early in life using minimally invasive techniques such as embolization and endovenous laser, by an experienced interventional radiologist.

Arteriovenous malformations

A subgroup of CLOVES syndrome patients develops a fast-flow vascular lesions or arteriovenous malformation (AVM). Most of these lesions are located in the paraspinal region and less frequently in the chest wall and extremities. Paraspinal AVM is associated with infiltrative fatty tissue in the posterior mediastinum that may extend into the spinal canal and cord, causing cord compression, venous hypertension and myelopathy.

Patients should be screened for these vascular lesions with an early MRI. If fast-flow anomalies or extension into the spinal canal are found, neurosurgical consultation and a dedicated spinal MRI, with sagittal and axial T2 and pre- and post-contrast T1 weighted sequences covering all potentially involved levels, are warranted. Patients who develop signs of spinal cord dysfunction (extremity weakness, urinary incontinence, constipation) should be promptly evaluated. Treatment may include spinal angiography, embolization and resection.

Depending on the degree of flow through a fast-flow lesion, cardiac function may be compromised. Evaluation by an anesthesiologist prior to a procedure may reveal the need for a cardiologist’s assistance in perioperative management.

Capillary malformation

Capillary malformations (also known as port wine stains) typically occur overlying truncal overgrowth and in the extremities. These stains are of limited clinical significance and usually require no treatment unless desired by the patient for cosmetic reasons.
Lymphatic vesicles often coexist and may require therapy.

Flashlamp-pumped pulsed dye laser (FPDL) therapy can be used to lighten the color of capillary stains.

Large lipomatous masses

Large lipomatous masses are most commonly located in the trunk and chest wall and can be associated with lymphatic and capillary malformations. These masses of variable size, are present at birth, and can be identified prenatally. Overgrowth can be unilateral or bilateral and may also extend into the abdominal wall, flank, gluteal and cervical areas as well as the extremities. Deeper extension may occur into the retroperitoneum, peritoneum, superior and posterior mediastinum, pelvis, pleural spaces and paraspinal muscles.

The clinical behavior of paraspinal-posterior mediastinal infiltrative tissue is distinct from the larger fatty masses. Paraspinal lesions can be hypervascular, aggressive and infiltrate into the epidural space and compromise the spinal cord and adjacent vessels.

Lipomatous overgrowth should be evaluated by a surgeon. Work up generally includes MRI of the affected areas. Surgical debulking of these lesions can improve mobility and quality of life. Removal of very large masses may also prevent growth disturbance of the underlying or nearby musculoskeletal structures (e.g. removal of a large chest wall mass may prevent rib cage deformity and resultant lung compression and restriction). When applicable, resection can include removal of cutaneous lymphatic vesicles, thereby reducing leaking and infection risk as well. Patients often require multiple staged operations. Lipomatous masses can regrow after resection, though this is difficult to predict for an individual patient.

Proper perioperative planning should be undertaken to prevent major complications such as thromboembolism. As mentioned above, initiation of perioperative anticoagulation and closure of veins deemed to be at high risk of initiating thromboemboli may be beneficial prior to a major operative resection. Multidisciplinary preoperative team meetings which include surgeons, anesthesiologists, interventional radiologists, hematologists, nurses and blood bank can be invaluable in preparing a team prior to large resections.

Maxillofacial asymmetry

Soft tissue overgrowth is typically caused by facial infiltrating lipomatosis, which can be associated with maxillofacial bony asymmetry and dental malocclusion. The cheek, lip, and underlying bone can be enlarged and cause psychological distress.

Facial and dental arch asymmetry should be evaluated by a plastic or maxillofacial surgeon early in life. Dental abnormalities are addressed by a dentist. Work up includes an MRI of the head and brain.

Brain asymmetry

Multiple types of brain abnormalities have been described in CLOVES syndrome including hemimegalencephaly, cerebral asymmetry, cerebral white matter lesions, cortical dysplasia/migrational anomalies. These findings can be associated with seizures and developmental delay.

Cerebral abnormalities and neurologic symptoms should be evaluated by a neurologist or neurosurgeon. Work up includes an MRI of the brain.

Epidermal nevus and moles

Epidermal nevi and moles in CLOVES syndrome are of limited clinical significance and may require no intervention beyond dermatologic screening and investigation of suspicious appearing moles.

Chest wall deformity

Chest wall deformity, which is typically associated with large overgrowth, should be evaluated by a pediatric surgeon.

Scoliosis

Scoliosis in CLOVES syndrome tends to be progressive. It can be secondary to paraspinal-truncal soft tissue masses and disordered musculature, vertebral and other anomalies but can also be a separate, primary finding.

Patients with CLOVES syndrome should be screened for scoliosis by early MRI and routinely with physical examinations. Scoliosis should be treated per the usual recommendations by a pediatric orthopedic specialist. It can be difficult to manage with orthotic care due to truncal overgrowth. Surgical treatment may be indicated to prevent further deformity, pulmonary decompensation, and spinal cord injury.

Tethered cord and neural tube defects

There is an increased risk of tethered spinal cord and neural tube defects (e.g. spina bifida and myelomeningocele) in CLOVES syndrome.

All patients with CLOVES syndrome should be evaluated clinically and screened for neural tube defects and tethered cord by spinal ultrasonography in the neonatal period. If early MRI study was performed and reliably characterized the spinal cord then an further ultrasonography is not necessary. If no imaging has been done at the time of first presentation, then a dedicated spinal MRI study is warranted.

Tethered spinal cord and neural tube defects should be managed and followed by a neurosurgeon with early detethering considered (if feasible) to prevent neurologic damage.

Paraspinal hypervascular-lipomatous overgrowth

Paraspinal Hypervascular-Lipomatous Overgrowth is characteristic of CLOVES syndrome. Elongated posterior mediastinal masses are located along the bilateral anterior paravertebral spaces and can mimic neurogenic tumors on cross-sectional imaging. Unlike overgrown tissue elsewhere, paravertebral lesions may be aggressive, and infiltrative with hypervascular, fast-flow malformations which may compromise the spinal cord and associated vessels. The tissue may extend into the spinal canal and cause compression of the thecal sac, spinal cord and nerve roots.

The natural history of these masses is variable. Many lesions remain stable in size and cause no signs or symptoms, while others can cause different types of neurologic injury, including mass effect on the spinal cord and nerve roots and high-flow/arteriovenous malformation, as described above.

Patients should be screened with an early MRI. Extension into the spinal canal should be evaluated and followed by a neurosurgeon. Work up includes a dedicated spinal MRI. The course of the behavior of these lesions should be evaluated with physical examination and annual spinal MRI study. Patients who develop signs of spinal cord dysfunction (extremity weakness, urinary incontinence, constipation) should be promptly evaluated and managed by a neurosurgeon. These masses may recur after partial surgical removal and follow-up is necessary.

Gastrointestinal involvement

Thickening of the anorectum and sigmoid colon is caused by circumferential venous and lymphatic malformation and may cause intestinal bleeding. Bleeding may also be caused by perianal lymphatic vesicles. Patients typically have slow, chronic bleeding leading to anemia. They may also experience episodes of acute, high volume bleeding. The presence of ectatic portomesenteric veins is associated with thrombosis and portal hypertension.

Splenomegaly and splenic lesions, thought to be multifocal lymphatic anomalies, can be present in CLOVES syndrome and typically of little clinical significance and therefore do not commonly require intervention.

Patients should be evaluated by a gastroenterologist and surgeon. Work up may include MRI study and colonoscopy. Anemia due to chronic bleeding may require iron supplementation or blood transfusions. Venous malformation can be treated with sclerotherapy, or surgical resection. For refractory bleeding, partial colectomy, anorectal mucosectomy, and coloanal pull-through may be considered. Ectatic portomesenteric veins, which can be visualized with MRI, CT scan or ultrasonography, can be managed initially with anticoagulation while surgical intervention is contemplated. A massively dilated, incompetent inferior mesenteric vein should be evaluated for ligation at its junction with the splenic vein to prevent siphoning of blood flow from the portal vein and resultant portal thrombosis.

Genitourinary involvement

Unilateral renal hypogenesis or agenesis and compensatory enlargement of the contralateral kidney are frequently present in CLOVES syndrome. Other findings include renal cysts, hydroureteronephrosis, heterogeneous renal parenchyma and renal malposition. There is an increased risk of Wilms tumors in CLOVES syndrome, occurring in ~3% of CLOVES syndrome patients studied. Wilms tumor prognosis is generally excellent, especially when found early.

Enlargement and thickening of the urinary bladder in CLOVES syndrome may assume an elongated configuration with anterosuperior displacement. Venous malformation in the urothelial lining of the bladder and urethra may cause bleeding with urination (hematuria). Some patients experience functional urinary abnormalities or incontinence.

Children with CLOVES syndrome should undergo screening renal ultrasonography every 3 months until the age of 8 years to monitor for the development of Wilms tumor.

• Experts recommended an initial renal ultrasound in the neonatal period which also can be used as a baseline for Wilms tumor screening.
• Unilateral renal hypogenesis or agenesis is usually of little clinical significance.
• Functional abnormalities and hematuria should be evaluated by a urologist. Neurological causes of functional abnormalities should be excluded. Work up may include MRI study and cystoscopy. Venous lesions can be treated with laser coagulation.

Other abdominal findings include inguinal hernias, undescended testicles and ascites. Groin and scrotal masses appearing to be inguinal hernias may in fact be lymphatic malformations extending from the retroperitoneum. Resection can be challenging due to investment within the vital spermatic cord structures. This should be anticipated prior to scheduled herniorrhaphy so the surgeon is prepared to undertake meticulous and lengthy resection rather than a straightforward hernia repair.

Limb abnormalities

Limb abnormalities should be evaluated early in life. When present, these abnormalities should be followed by a team familiar with the relevant components of overgrowth.

Asymmetric girth or length of the upper or lower extremities is a common finding in CLOVES syndrome. Diffuse overgrowth typically affects bones, muscles, nerves and fat. This enlargement may involve specific regions of the hand, foot, forearm, or leg and not necessarily the entire limb. Fat overgrowth in the affected portion of the limb may be markedly large and accounts for most of the enlargement.

Overgrowth and other musculoskeletal malformations may lead to secondary problems, such as early arthritis, contractures, stiff joint and neuromas. Capillary malformations and anomalous veins may also be present.

Developmental dysplasia of the hip and dislocation may exist particularly with large overgrowth of the pelvic and gluteal regions.

Knee deformities include valgus deformity, dysplasia, dislocation and chondromalacia patellae.

Common deformities of the foot include large, wide triangular foot with broad forefoot wide metatarsal spaces, wide sandal gap between first and second toes, lipomatous masses, macrodactyly (large toes), polydactyly (extra toes), syndactyly (fused toes), talipes, and furrowed soles. Lymphatic vesicles may affect the feet, especially the toes. These deformities may make finding appropriate shoe wear difficult.

Common deformities of the hands include broad spadelike asymmetric digits, macrodactyly, polydactyly, syndactyly, ulnar deviation of the digits and a laxity of collateral ligaments. Some digits and thumbs may be minimally enlarged and deviated. Significant deviation of the thumb is frequently seen Capillary malformations of the fingers are common. Fingers affected by macrodactyly may exhibit significant stiffness starting from birth. Fatty overgrowth of the forearm and hand may be seen. Dorsally-located lymphatic malformations of the digits may pose functional problems if large. Premature osteo-arthritis is common in the 3rd and 4th decades of life.

• Leg length discrepancy: Standard follow up with physical exam and motion radiography should be established. Shoe lift and epiphysiodesis of long bones or digits may be considered.
• Debulking of the overgrown adipose and vascular tissues can provide functional and cosmetic benefits. Staged reconstruction is often indicated. Other treatment options include osteotomies, ostectomies, ray resection or amputations of markedly overgrown digits or limb.
• Arthroscopy may be helpful in assessing the joint changes related to peri- and intra-articular vascular malformations. Sclerotherapy may minimize pain related to venous malformations. Hematologic evaluation prior to major orthopedic procedures is important to prevent thromboembolism.
• Debulking of lymphatic malformations of the digits may help with function. Lymphatic malformations and fatty overgrowth of the palm are more difficult to address due to presence of tendons and neurovascular structures.
• Syndactyly and polydactyly treatment should be considered in light of functional requirements. If the syndactyly involves an overgrown, stiff digit, simultaneous amputation will provide ample skin for closure of the webspace.
• Deviation of the thumb can be challenging, possibly requiring osteotomy and/or amputation of the bulk or a border digit depending on the degree of deformity.

CLOVES syndrome prognosis

As CLOVES syndrome is rare disease that affects each child differently and was only defined in 2007, there are many unknowns still.

Your child’s long-term outlook or prognosis will depends on many factors, including:

• Age at diagnosis (the earlier treatment is started, the better)
• Specific symptoms
• Overall health

Many children with CLOVES syndrome do very well when the disease is mild and diagnosed early. Your child’s doctor will give you specific information about a recommended plan of care and long-term outlook.

Cervical kyphosis

Cervical kyphosis is when the cervical spine (the neck) curves in the opposite direction than normal ¹⁾. Cervical kyphosis can be either regional or global, and has been shown to be associated with reduced quality of life ²⁾. Cervical kyphosis can lead to problems ³⁾. However, most cervical kyphosis isn’t serious. But if the curve is severe, bones in the spine called vertebrae might pinch the spinal cord. This can damage the spinal cord.

The spinal cord is the body’s central communication system (see Figure 3 below). It’s a tube of nerves that runs inside the spine. The nerves branch out to every part of the body. They send messages between the brain and the rest of the body. If damage is very bad, the nerves can’t send important signals like telling the lungs to breathe or blood to move around the body.

Cervical kyphosis isn’t common. It can happen to any child, but kids who have it often have another health problem too.

Parents can’t stop cervical kyphosis from happening. But they can help kids get the best care.

It’s important to diagnose spine problems early. If kids don’t get treatment, some may end up with spinal cord damage that can’t be fixed.

Here are tips for avoiding problems:

• See a doctor if your child has trouble with head movements or neck pain. Neck trouble needs to be checked out to be sure it’s not something serious.
• Go to all medical appointments if your child has cervical kyphosis. Even a small curve can get bigger as a child grows. The care team will want to keep watching for possible problems.
• If your child had surgery, ask the care team when you should bring your child for follow-up visits. The will check your child to be sure the kyphosis does not come back.

The care team is a resource — for you and your child. They can answer questions and help your child get the best treatment. So reach out for help and answers when you need to.

Managing cervical kyphosis is challenging for the spinal surgeon, and setting realistic surgical goals and meticulous preoperative planning can achieve the optimal clinical outcomes, while managing the condition ⁴⁾.

Surgical treatment of this challenging pathology is a daunting task and focuses on neural decompression, and improvement in alignment and stabilization of the cervical spine ⁵⁾. Flexible deformities are preferably managed by posterior stabilization provided the alignment of cervical spine is restored optimally. Fixed deformities are treated using skeletal traction for a brief period before deciding the surgical approach. An anterior approach is preferable in short segment cervical kyphosis with anterior compression of spinal cord requiring one to two-level corpectomy. A circumferential approach has the advantage of rigid fixation and restoration of posterior tension band. Though radical, it reduces the chances of instrumentation failure, graft extrusion, and pseudoarthrosis. As the benefits of this approach outweigh the potential complications, the morbidity of circumferential cervical spine surgeries is decreased by use of proper techniques and experience ⁶⁾.

Figure 1. Cervical kyphosis

Figure 2. Normal cervical spine

Figure 3. Spinal cord

Figure 4. Cervical spine

Figure 5. Cervical spine anatomy

Figure 6. Cervical kyphosis treatment algorithm

[Source ⁷⁾ ]

Cervical kyphosis causes

Kids can get cervical kyphosis in three ways:

1. They are born with it.

• This is called congenital cervical kyphosis. No one knows what causes it. Doctors do know that it has nothing to do with anything a mom did when she was pregnant.

2. Something goes wrong in the body.

• This is called acquired cervical kyphosis. Lots of different things can cause it, such as:
  • injury to the bones of the spine or the ligaments around them
  • infection
  • tumors
  • surgery
  • radiation therapy for cancer

3. They have another condition that causes them to get kyphosis.

For example:

• skeletal dysplasia
• spina bifida
• osteogenesis imperfecta
• neurofibromatosis type 1

Cervical kyphosis signs and symptoms

Here are some things parents may notice when a child has cervical kyphosis:

• an unusual curve in the child’s neck
• the child has trouble looking up or turning his or her head
• the child has neck pain

If the curve is sharp enough to pinch the spinal cord, kids might have these problems:

• pain, tingling, loss of feeling, or weakness
• be unable to move their arms or legs
• trouble peeing or pooping
• accidents because they can’t control when they pee or poop (called incontinence)

Cervical kyphosis diagnosis

If you think your child has a neck problem, make an appointment with your pediatrician. The doctor, nurse, or physician assistant will ask about what’s going on. They will order tests like X-rays.

If the pediatrician thinks your child needs specialized help, he or she will send you to a specialist. Specialists who treat kids with kyphosis are:

• neurologists (experts in the nervous system)
• neurosurgeons (doctors who operate on the brain and spinal cord)
• orthopedists (experts in bones, muscles, and joints)

Radiographic evaluation

Preoperative planning for surgical treatment of the cervical spine begins with assessing the plain and dynamic radiographs of the cervical spine. Various parameters used to assess cervical spine include cervical lordosis (CL), chin to brow vertical angle (CBVA), C2–C7 sagittal vertical axis (C2–C7 SVA), T1 slope (T1S), neck tilt, and thoracic inlet angle (TIA) ⁸⁾. Figure 7 shows these parameters measured using plain X-ray. Advanced radiological investigations such as computed tomography (CT) myelogram and/or magnetic resonance imaging (MRI) are useful to determine the compression of the spinal cord. MRI also aids the assessment of the intervertebral discs, presence of scar tissue, and posttraumatic integrity of the posterior ligamentous complex.

Figure 7. Cervical kyphosis preoperative planning

Footnote: Parameters measured using plain X-ray. a: C2–C7 sagittal vertical axis; b: T1 slope; c: thoracic inlet angle; and d: neck tilt.

[Source ⁹⁾ ]

Cervical kyphosis treatment

Cervical kyphosis treatment depends on the child’s age and how bad the curve is. Here are some of the things doctors use:

• Bracing. Children may wear a neck brace to treat cervical kyphosis.
• Physical therapy. Physical therapists work with kids to help improve flexibility and posture and reduce pain.
• Pain management. If kids have pain, doctors and nurses prescribe medicines and other pain management techniques.
• Surgery. Kids need surgery when a curve puts pressure on the spinal cord in a way that may cause nerve damage. Kids who also have diseases that make their bones weak or slow to heal may need more than one operation.

Preoperative planning

The first step in appropriate preoperative planning is to understand the underlying cause and the magnitude of the deformity. It is imperative to know that cervical kyphosis in the subaxial spine is associated with compensatory hyperlordosis at the cervico–occipital junction ¹⁰⁾. This is important in planning cranio–cervical fusion ¹¹⁾.

The main goals of cervical kyphosis surgery are ¹²⁾:

1. To restore subaxial cervical lordosis to 15°, thus improving the spinal alignment and balance;
2. To decompress the spinal cord and nerve roots;
3. To restore C2–C7 sagittal vertical axis to <40 mm;
4. To restore the horizontal gaze of vision;
5. To attempt to normalize the T1 slope; and
6. To achieve good fusion to reduce neck pain.

The type of approach (anterior, posterior, or combined) is decided using MRI and/or CT myelogram, depending upon the severity and location of the neurological compression. It is also useful to determine the extent of adequate neurological decompression ¹³⁾. The most important and critical factor to determine the type of surgery (anterior, posterior, or combined) is the flexibility of the deformity ¹⁴⁾. Dynamic radiographs help to determine the ability of deformity correction by altering the position, while a CT scan provides additional information about bony ankylosis at disc space and facet joints.

Cervical kyphosis surgery

Surgical planning involves calculating the amount of correction required for the radiographic parameters. Although there is no ‘normal’ range described, the current literature recommends that T1 slope to C2–C7 lordosis should be <15°, C2–C7 sagittal vertical axis should be <40 mm, and an acceptable chin to brow vertical angle is −10 to +20 ¹⁵⁾.

The magnitude of kyphosis, location of the compression, flexibility of the deformity, presence and location of the bony ankyloses, and history of previous surgery/laminectomy determines the specific surgical approach. Broadly, cervical kyphosis can be classified as fixed or flexible. Flexible deformities usually require realignment surgery, whereas more complex, fixed deformities require surgical correction using a combined (anterior+posterior) approach or osteotomies.

Anterior approach

An anterior approach is preferred in patients with a fixed deformity. Anterior techniques rely on restoring segmental lordosis, thus it is crucial to evaluate facet ankylosis using CT. Kyphosis correction with an anterior fusion, and with or without instrumentation, has been described in the literature ¹⁶⁾.

In a retrospective analysis of 14 patients who underwent anterior corpectomy with strut grafting and without instrumentation, Zdeblick and Bohlman ¹⁷⁾ reported that at the average follow-up period of 27.9 months, Nurick scores improved from 3.6 (preoperative) to 1.3 (postoperative). No patient had neurological deterioration. The mean preoperative kyphosis was 45°, mean postoperative kyphosis was 13°, and mean kyphosis correction was 32°. The authors reported an average loss of 4° correction at follow-up. Three patients had their bone grafts dislodged in the immediate postoperative period despite immobilization using a halo vest.

In another retrospective study, Zdeblick et al. ¹⁸⁾ reported the functional outcome of anterior corpectomy and strut grafting in patients with failed anterior cervical diskectomy and fusion and kyphosis (n=8). Revision surgery was performed with an average duration of 32 months from the index procedure. The average kyphosis correction was 30°. Seven out of eight patients had excellent or good functional outcome; however, poor outcome was reported in one patient. This patient had pseudoarthrosis and recurrence of myelopathy, and underwent revision surgery.

In a series of 18 patients, Riew et al. ¹⁹⁾ analyzed 18 patients with postlaminectomy cervical kyphosis that were treated with anterior cervical corpectomy and fusion. The mean kyphosis correction at final follow-up was 6°. Eight out of 18 patients had demonstrated kyphosis correction. The authors also reported an increment in kyphosis by 10° due to the subsidence of strut graft. The major focus of this study was to study the complications associated with this procedure. The authors reported a complication rate of >50% related to surgery alone, including failure of fusion, dislodging or subsidence of the graft, and an increment in kyphosis. They also reported that the halo vest provided insufficient immobilization and was not adequate to prevent complications related to the strut graft.

Following further advances in instrumentation systems, anterior cervical decompression and fusion with plate reconstruction was described as the only anterior procedure for the treatment of cervical kyphosis. Herman and Sonntag ²⁰⁾ retrospectively analyzed 20 patients undergoing anterior cervical corpectomy with fusion and plate fixation for treatment of postlaminectomy kyphosis. The mean preoperative kyphosis was 38°. At a mean follow-up of 28 months, all patients showed an evidence of solid fusion with a mean postop kyphosis of 16°. A mean deformity correction of 20° was achieved with intraoperative traction. The majority of complications in this study were not related to surgical technique, and only one (5%) patient had implant-related complications (screw pulled out).

In a case series of four patients of postlaminectomy kyphosis treated with anterior decompression and fusion with platting, Gulmen and Zileli ²¹⁾ reported good clinical outcome in three patients, and around 20° of mean improvement in kyphosis. One of the four patients died 20 days after surgery due to respiratory complications.

Ferch et al. ²²⁾ retrospectively studied 28 patients undergoing anterior decompression with instrumented fusion for cervical kyphosis. A total of 93% (26/28) of patients were available for analysis. The average follow-up period was 25 months. The mean preoperative local and regional kyphosis was 12 and 10, respectively, and the average local and regional kyphosis correction was 14 and 11, respectively. At final follow-up, the modified Japanese Orthopedic Association (mJOA) scores improved in 11 patients, whereas it remained stable in 15 patients. Deterioration of the mJOA score was reported in one patient. Neck pain scores remained unchanged in the preoperative and postoperative periods.

Steinmetz et al. ²³⁾ proposed hybrid surgery for postlaminectomy cervical kyphosis correction. This technique combined corpectomy and discectomy with anterior cervical plate fixation. In a retrospective study of 10 patients, the authors reported improvement in all patients, and three patients reported complete resolution of symptoms. The average preoperative kyphosis was 13.2°, while that at final follow-up was −8.4°. A mean cervical kyphosis correction of 21.6° was observed. However, one limitation of this study was the low duration of follow-up. Three patients experienced complications; one had postoperative dysphagia and two suffered hoarseness of the voice.

In a retrospective study of prospectively collected data, Park et al. ²⁴⁾ analyzed 23 patients undergoing anterior reconstruction surgery using a hybrid technique and plate fixation for postlaminectomy kyphosis. The average follow-up was 44.5 months. The mean preoperative kyphosis was 20.9°, while that at the final follow-up was −9.6°, with mean cervical kyphosis correction 30.5° for cervical kyphosis. There was significant improvement in the neck disability index, Visual Analog Scale (VAS) scores, and Nurick grades. All patients showed improved neurology, while nine patients had complete resolution of symptoms. The authors concluded that augmentation of fusion with the plate decreased the graft-related complications ²⁵⁾. However, posterior instrumented fusion to the construct was added in patients undergoing corpectomy at more than three levels. Almost 13% of patients in this series showed graft-related complications.

Posterior approach

A posterior-only approach is less commonly implicated in the management of cervical kyphosis. It is commonly used in conjunction with an anterior approach for circumferential fusion, and is indicated in flexible deformities, when kyphosis correction is achieved by positioning of head or traction, and whenever there is no anterior compression ²⁶⁾. Abumi et al. ²⁷⁾ retrospectively analyzed 30 patients undergoing cervical kyphosis correction with the use of cervical pedicle screws. Of these patients, 17 had flexible kyphosis and were managed with an entirely posterior procedure. The mean preoperative kyphosis was 28.4° that improved to 5.1° at final follow-up. All patients had fusion at the final follow-up. Transient nerve root complications related to placement of the pedicle screw was reported in two patients.

Lateral mass screws are the preferred modality of fixation owing to a low complication rate compared with that of pedicle screws. However, biomechanically, they are inferior to pedicle screws. In a systemic review, Coe et al. ²⁸⁾ found lateral mass screws provided an adequate fusion rate and an acceptable deformity correction. Gerling et al. ²⁹⁾ studied nine patients with dropped head deformity and flexible kyphosis due to cervical myopathy who underwent deformity correction and posterior instrumented arthrodesis. The mean follow-up duration was 6 years. Four patients had primary cervical myopathy, while the other 5 patients had secondary cervical myopathy due to radiotherapy. Outcome measures were reported using Odom’s criteria, VAS scores for neck pain, and patient satisfaction ratings. All patients showed improvement in Visual Analog Scale (VAS) scores at the final follow-up. Seven patients had an excellent outcome, while two patients had a fair outcome as reported by Odom’s criteria and patient reported measures. Though 11 complications were reported, none of the patients had neurological deterioration.

Combined approach

White and Panjabi ³⁰⁾ proposed the idea that corpectomy in patients with postlaminectomy kyphosis further destabilizes the spine. The right and left elements of the vertebrae are only connected by soft tissue that has significantly less resistance to torsion and axial forces. An anterior graft in the absence of posterior elements bears the entire axial load, which may not be prevented by halo vest immobilization alone. Therefore, there is an increased risk of graft dislodgement or subsidence. The authors strongly recommended the addition of posterior instrumented fusion in patients undergoing anterior corpectomy and fusion for postlaminectomy kyphosis ³¹⁾.

Posterior osteotomy

Patients with rigid cervical kyphosis along with ankylosed facet joints require the use of posterior-based osteotomies for deformity correction. Although Mason et al. ³²⁾ first described posterior-based open wedge osteotomy for the treatment of cervical kyphosis, many modifications of this procedure were described for treatment of cervical kyphosis in ankylosing spondylitis. MacMaster ³³⁾ reported 15 patients with ankylosing spondylitis with severe cervical kyphosis managed by extension osteotomy at C7–T1. After osteotomy, kyphosis correction was achieved by extension of the head using spinal cord monitoring. Halo traction or internal fixation was used postoperatively to maintain the kyphosis correction. The mean cervical kyphosis was 23°, and was corrected to a mean lordosis of 31°, providing a mean kyphosis correction of 54°. However, internal fixation (Luque rods and wiring) was used in only three patients. Four patients in this series had subluxation at the osteotomy site. As this procedure was dependent on lengthening the anterior column, it was associated with a high rate of morbidity.

1) Pedicle subtraction osteotomy

Pedicle subtraction osteotomy is a posterior closing wedge osteotomy involving resection of a wedge of the vertebral body along with superior and inferior articular processes and lamina ³⁴⁾. It is most commonly performed at C7 owing to the anatomy of the vertebral artery as well as the wide diameter of spinal canal at C7–T1 ³⁵⁾.

Deviren et al. ³⁶⁾ analyzed 11 patients that underwent pedicle subtraction osteotomy at the cervicothoracic junction for cervicothoracic sagittal imbalance. Then patients underwent pedicle subtraction osteotomy at C7, whereas one patient underwent T1 pedicle subtraction osteotomy. Outcome measures were reported using the Neck Disability Index (NDI) scores, the 36-item Short-Form Health Survey (SF-36) scores, and the VAS scores for neck pain in nine out of the 11 patients that were followed for a mean duration of 23 months. The mean kyphosis correction was 19°, and mean chin to brow vertical angle correction was 36.7°. There was significant improvement in NDI, VAS, and SF-36 scores in all patients. None of the patients had any neurological complications.

2) Circumferential osteotomy

Abumi et al. ³⁷⁾ reported on 13 patients with fixed and rigid cervical kyphosis who were managed using combined anterior and posterior procedures. The mean preoperative kyphosis was 30.8°, and the mean cervical kyphosis at final follow-up was 0.5°. All patients had complete fusion at final follow-up. The authors concluded that circumferential osteotomies along with posterior shortening procedures with the use of pedicle screw instrumentation provided the best cervical kyphosis correction with bony fusion ³⁸⁾. Mummaneni et al. ³⁹⁾ retrospectively analyzed 30 patients with cervical kyphosis undergoing circumferential procedures. Anterior procedures included discectomies and corpectomies/osteotomies at one or more levels, while posterior procedures included decompression and/or osteotomies with lateral mass or pedicle screw fixation. A total of 27 patients were available for analysis at mean a follow-up period of 2.6 years. Ishihara kyphosis indices improved from a preoperative mean of −17.7 to a postoperative mean of +11.4. Furthermore, the mJOA scores improved from 10.5 to 15, while the Nurick scores improved from 3.2 to 1.3. The fusion rate was reported to be 95%. This study had significant complication rates; 33% of patients had major and minor complications, while there were four deaths. None of the patients had neurological worsening. The authors concluded that circumferential reconstruction is efficacious in treating cervical kyphosis adequately. O’Shaughnessy et al. ⁴⁰⁾ analyzed 16 patients who underwent anterior and posterior reconstruction for fixed cervical kyphosis. The mean follow-up period was 4.5 years. The C2–C7 Cobb angle improved from a preoperative mean of +38° to a mean of −10° at final follow-up, yielding a mean kyphosis correction of 48°. The mean Nurick scores improved from 2.4 prior to surgery to 1.5 at final follow-up. Excellent and good outcomes were reported in 38% and 50% of patients, respectively, as per Odom’s criteria, while the fair and poor outcome groups contained 6% of the patients each. All patients had good bony fusion and maintenance of correction at final follow-up. Nottmeier et al. ⁴¹⁾ retrospectively reviewed 41 patients undergoing circumferential reconstruction for rigid cervical kyphosis. Patients were followed for mean period of 19 months. The mean preoperative kyphosis of 18° improved to 4° of lordosis at final follow-up, resulting in a mean kyphosis correction of 22°. There was no loss of correction in any patient, while a fusion rate of 97.5% was obtained. Two patients had neurological complications (one quadriparesis and one transient C8 radiculopathy). Ogihara and Kunogi ⁴²⁾ reported three patients undergoing single stage anterior and posterior fusion surgery for cervical kyphotic deformity correction using an intervertebral cage and lateral mass screws. All patients were followed up for a minimum period of 61 months and showed improved symptoms following surgery. All three patients had complete fusion and maintenance of correction at final follow-up. The authors concluded that the combination of anterior cages and lateral mass screws was considered a safe and effective procedure for the cervical kyphosis correction. Shah et al. ⁴³⁾ reported a case of neurofibromatosis with buckling kyphosis of cervical spine. The patient was treated with circumferential osteotomy in a staged procedure. In the first stage, anterior cervical corpectomy with soft tissue release was performed. In the second stage, posterior fusion was carried out using lateral mass screws.

Comminuted fracture

Comminuted fractures are fractures where the bone shatters into three or more pieces. Comminuted fractures include a very heterogeneous group of fractures from a 3 part humeral head fracture to a multi-part fracture of the femur following a high-energy road traffic accident. Closed, mildly comminuted fractures can be treated with a plate in buttress function, if the main fragments allow insertion of a sufficient number of screws. Internal fixators can also be used as buttress implants, and have the advantage of preserving cortical blood supply and requiring only two screws per fragment (Figure 1).

Figure 1. Comminuted fracture

Comminuted fracture causes

It takes a lot of force for someone to get a comminuted fracture. A car accident or serious fall, for instance, can cause this type of break.

Comminuted fracture treatment

Someone with a comminuted fracture will probably need surgery. After surgery, the person will wear a splint or cast for a while to keep the bone from moving while it heals.

Buckle fracture

Buckle fracture also called torus fracture, is an incomplete fracture of the shaft of a long bone that occurs when a bone “buckles” or slightly crushes in on itself and is characterized by bulging of the cortex of the bone. The topmost layer of bone on one side of the bone is compressed, causing the other side to bend away from the growth plate. Torus or buckle fracture occurs in the transition zone between metaphyseal and diaphyseal bone ¹⁾. Torus (buckle) fractures of the distal forearm are common injuries in children and young adolescents, typically occurring after a fall on an outstretched arm ²⁾.

The most common type of buckle fracture in children occurs in the forearm, near the wrist, usually after a child falls onto an outstretched arm. The injury affects the radius bone in particular. The bone will have a very small fracture, which is so minor that it may be difficult to see on X-ray (Figure 2). The wrist may be tender, slightly swollen, and painful to move. There is no deformity in the wrist, which means the wrist will not be out of its usual shape.

Buckle fracture or torus fracture is a stable fracture, meaning that the broken pieces of bone are still in position and have not separated apart (displaced). Buckle fractures or torus fractures are stable due to the thick periosteum present in this patient population and unlike other pediatric wrist and forearm fractures, the risk of future displacement is minimal ³⁾.

Buckle fractures are treated by wearing a removable backslab (a partial cast held in place with bandages) or ready-made splint, which should be worn as much as possible but can be removed for bathing or showering. An arm sling is optional, and may help reduce any pain or discomfort.

Buckle fractures are more common in children, especially aged 5-10 years, due to the elasticity of their bones. In adults, the commonest form of buckle fracture seen is a buckle fracture of the ribs.

Buckle fracture key points to remember:

• A buckle fracture in the wrist is a small area of compressed bone.
• Your child should wear a removable backslab (partial cast) or splint for three weeks. A sling may help reduce discomfort.
• Most children will not need a follow-up appointment or X-ray, because buckle fractures usually heal quickly without any problems.
• Avoid contact sports for six weeks after the injury.

Figure 1. Buckle fracture

Figure 2. Buckle fracture of the distal radius

Footnote: A buckle fracture of the distal radius in a six-year-old child. Arrows point to buckling of the cortex.

[Source ⁴⁾ ]

Figure 3. Buckle fracture splint

Buckle fracture causes

Children love to run, hop, skip, jump and tumble, all of which are activities that could potentially result in a buckle fracture to the forearm should an unexpected fall occur. In most cases, forearm fractures in children are caused by:

• A fall onto an outstretched arm
• A fall directly on the forearm
• A direct blow to the forearm

Torus fractures or buckle fractures, are incomplete fractures of the shaft of a long bone that is characterized by bulging of the cortex. They result from trabecular compression due to an axial loading force along the long axis of the bone. They are usually seen in children, frequently involving the distal radial metaphysis.

Strictly speaking, a torus fracture refers to a circumferential buckle fracture ⁵⁾. However, the terms are often used interchangeably.

Cortical buckle fractures occur when there is axial loading of a long bone. This most commonly occurs at the distal radius or tibia following a fall on an outstretched arm; the force is transmitted from carpus to the distal radius and the point of least resistance fractures, usually the dorsal cortex of the distal radius.

Buckle fracture symptoms

A forearm buckle fracture usually results in severe pain. Your child’s forearm and hand may also feel numb, a sign of potential nerve injury.

Symptoms of a broken arm may include:

• Immediate, severe pain
• Swelling and tenderness
• Numbness in the forearm, hand or elbow
• Deformity of the forearm, elbow or wrist
• Difficulty turning or rotating the forearm

Additionally, your child may feel the need to support the injured arm with their other hand.

Buckle fracture diagnosis

Diagnosing a forearm torus fracture typically begins with a physical examination of your child’s arm, wrist and elbow. The physician will look for any deformity of the arm, as well as swelling, tenderness, and an inability to rotate the affected arm.

In most cases, clinicians will recommend X-rays of your child’s forearm to confirm the diagnosis and determine the extent of your child’s injury. X-rays produce images of bones and help doctors identify the type of fracture so they can recommend the best treatment for your child.

In addition to a physical exam and X-rays, your child may also undergo:

• Range of motions tests to determine how the injury is affecting your child’s movement and dexterity
• Nerve assessment tests to determine if the injury has damaged or compressed any nerves in your child’s arm or hand

The more information we have about your child’s condition, the better we can treat their unique injury.

Buckle fracture treatment

Buckle fractures or torus fractures are usually treated with a pre-made wrist splint or a removable Plaster of Paris backslab (a partial cast held in place with bandages), which should be worn as much as possible but can be removed for bathing or showering. Both these methods, combined with simple painkillers such as acetaminophen (paracetamol) and ibuprofen, will help control your child’s pain. An arm sling is optional, and may help reduce any pain or discomfort.

Historically torus fractures or buckle fractures were managed with cast immobilization, and serial radiographic follow-up in an orthopedic outpatient setting ⁶⁾.

The traditional management of pediatric torus fractures or buckle fractures of the distal forearm has mirrored that of other fractures in this region, including cast immobilization and serial radiographic and clinical follow-up to assess for displacement until fracture union ⁷⁾. However, emerging literature over the last two decades has supported a ‘minimalist’ approach to managing these injuries. Van Bosse et al ⁸⁾ described treatment with removable splint application at time of injury, appropriate patient and caregiver counseling, a short (three to four week) period of immobilization and either self-discontinuation of the splint at home or a single follow-up appointment with clinical examination only. Radiographs become necessary only in the setting of re-injury or continued pain after the treatment period. Numerous other studies have highlighted safe and efficacious management of these injuries in a similarly ‘minimalist’ fashion ⁹⁾. The recent National Institute for Health and Care Excellence guidelines ¹⁰⁾ advocate management of torus fractures with nonrigid casts or splints. The patient can remove both of these without the need for further radiographs or follow-up ¹¹⁾.

In addition to pre-fabricated and removable splints, multiple other non-casting alternatives have been found to be equally safe in the management of paediatric torus fractures of the distal forearm. Soft bandage ¹²⁾ and soft cast ¹³⁾, neither of which require a physician visit for removal, have both been demonstrated to be acceptable treatment options. In the appropriately selected patient, home-based removal of immobilization can further simplify management and has been demonstrated to have equivalent outcomes to clinic-based reexamination and removal ¹⁴⁾. By eliminating the additional orthopedic clinic visits for cast removal and radiographic exams, these management approaches theoretically minimize the burden to the caregiver and patient while simultaneously reducing treatment cost ¹⁵⁾.

Care at home

Buckle injuries may be painful. Although immobilizing the arm with the backslab or splint will help to reduce the pain, additional pain relief (e.g. paracetamol) is sometimes needed. Give the pain relief medication as required, following the directions on the packet or as directed by the doctor.

Never cut or attempt to modify the cast, and make sure you avoid getting it wet.

Buckle fracture healing time

A stable fracture, such as a buckle fracture, may require 3 to 4 weeks in a cast.

Follow-up

Because buckle injuries are stable and heal quickly without problems, most children will not need a follow-up appointment with the doctor or hospital. Further X-rays or physiotherapy are usually not required.

Three weeks after their injury, your child can just stop wearing their backslab or splint.

After the backslab or splint is removed

Wrist movement may be a little stiff and sore at first. Contact sports (or rough and tumble play) should be avoided for six weeks after the injury.

Take your child to your doctor if:

• your child’s wrist remains very painful or swollen three weeks after the injury
• your child will not use their wrist, hand or fingers within two to three days of the back slab or splint being removed.

Jumper’s knee

Jumper’s knee also called patellar tendinitis or patellar tendinopathy, is a painful condition of the knee caused by small tears in the patellar tendon that mainly occurs in sports requiring strenuous jumping ¹⁾. It is appropriate to mention that patellar “tendinitis” is a misnomer as the condition is felt by many clinicians to be more tendinosis than it is tendinitis ²⁾. In published studies, it is noted that classic inflammatory cells are usually absent ³⁾. The patellar tendon is the cord-like tissue that joins the patella (kneecap) to the tibia (shinbone). The patellar tendon works with the muscles at the front of your thigh to extend your knee so that you can kick, run and jump. The tears are typically caused by accumulated stress on the patellar or quadriceps tendon. As the name implies, jumper’s knee is common in athletes from jumping sports such as volleyball, track (long and high jump), and basketball. Jumper’s knee has a male predominance ⁴⁾. However, even people who don’t participate in jumping sports can get patellar tendinitis. Contrary to traditional belief, jumper’s knee does not involve inflammation of the knee extensor tendons. Studies dating back 40 years describe jumper’s knee as a degenerative condition. Jumper’s knee is a clinical diagnosis made through detailed history taking and a physical exam. Ultrasound can facilitate the diagnosis, as this imaging study is readily available and affordable. Treatment mainly revolves around conservative measures such as reducing activities that place loading impact on the knee. For knee pain, try self-care measures first, such as icing the area and temporarily reducing or avoiding activities that trigger your symptoms. Once the pain subsides, restoration of function is achieved through physical and exercise therapy. Surgery usually remains the last resort for chronic refractory cases.

Figure 1. Patella tendon (ligament)

Figure 2. Jumper’s knee

Jumper’s knee staging

Blazina et al. ⁵⁾ first used the term jumper’s knee in 1973. They also classified the pathology by stage according to the onset of pain in relation to physical activity. This classification along with its modifications are still widely employed. Blazina et al. suggest 4 stages ⁶⁾:

1. Pain after sports activity
2. Pain at the beginning of sports activity yet disappearing with warm-up and sometimes reappearing with fatigue
3. Pain at rest and during activity
4. Rupture of the tendon

It may be useful to classify the pathology into 3 stages according to the duration of symptoms ⁷⁾:

1. Acute when symptoms have been present for 0 to 6 weeks
2. Sub-acute when symptoms have been present between 6 to 12 weeks
3. Chronic after more than 3 months

Jumper’s knee causes

Jumper’s knee is an overuse injury of the knee extensor mechanism due to repetitive mechanical stress from athletic activities requiring movements such as jumping, landing, acceleration, deceleration, and cutting ⁸⁾. Micro-tearing of the knee extensor tendons can arise after constant repetition of these movements during a single exercise session or if there is insufficient rest between sessions. The component of the knee extensor mechanism most likely to be affected is the inferior pole of the patella where the patellar tendon inserts. Other less frequently involved regions of the knee are at the insertion of the quadriceps tendon to the superior pole of the patella and where the patellar tendon inserts into the tibial tuberosity ⁹⁾. For purposes of simplicity, and considering that the majority of the cases for jumper’s knee are due to a problem on the patellar tendon at its insertion in the inferior patella, some authors have use the term patellar tendinopathy with jumper’s knee interchangeably.

There are several intrinsic factors of the knee that predispose to this pathology. These include ligamentous laxity, excessive Q-angle of the knee, abnormal patellar height, previous ongoing inflammation of the knee and excessive force generation on the knee. Other factors can also lead to the development of the jumper’s knee such as excessive volume and frequency of training, the athlete’s performance level, and the hardness of the ground where the sport is practiced ¹⁰⁾.

Pathophysiology

Overload on the knee extensor tendons will cause it to weaken progressively, eventually leading to failure. Microscopic failure occurs within the tendon at high loads and eventually leads to alterations at the cellular level, which undermine its mechanical properties. Tendon micro-trauma may cause individual fibril degeneration due to stress across the tendon. As the fibril degeneration becomes ongoing, chronic tendinopathy will ensue ¹¹⁾.

Examination of the tendon under ultrasound shows three pathologic changes. At first, there will be edema along the damaged tendon fibers. The affected tissue is swollen and thickened, but still homogenous. The second is a “stage with irreversible anatomical lesions,” the tendon has a heterogeneous appearance with hypoechoic and hyperechoic images without edema (granuloma). At this point, the tendinous envelope is still more or less well defined. In the final stage of the lesion, the tendinous envelope is irregular and thickened. Its fibers appear heterogeneous, yet the swelling has disappeared ¹²⁾.

Risk factors for jumper’s knee

A combination of factors may contribute to the development of jumper’s knee, including:

• Physical activity. Running and jumping are most commonly associated with jumper’s knee. Sudden increases in how hard or how often you engage in the activity also add stress to the tendon, as can changing your running shoes.
• Tight leg muscles. Tight thigh muscles (quadriceps) and hamstrings, which run up the back of your thighs, can increase strain on your patellar tendon.
• Muscular imbalance. If some muscles in your legs are much stronger than others, the stronger muscles could pull harder on your patellar tendon. This uneven pull could cause tendinitis.
• Chronic illness. Some illnesses disrupt blood flow to the knee, which weakens the tendon. Examples include kidney failure, autoimmune diseases such as lupus or rheumatoid arthritis and metabolic diseases such as diabetes.

Jumper’s knee prevention

To reduce your risk of developing jumper’s knee, take these steps:

• Don’t play through pain. As soon as you notice exercise-related knee pain, ice the area and rest. Until your knee is pain-free, avoid activities that put stress on your patellar tendon.
• Strengthen your muscles. Strong thigh muscles are better able to handle the stresses that can cause jumper’s knee. Eccentric exercises, which involve lowering your leg very slowly after extending your knee, are particularly helpful.
• Improve your technique. To be sure you’re using your body correctly, consider taking lessons or getting professional instructions when starting a new sport or using exercise equipment.

Jumper’s knee symptoms

Pain is the first symptom of jumper’s knee, usually between your kneecap and where the tendon attaches to your shinbone (tibia).

Initially, you may only feel pain in your knee as you begin physical activity or just after an intense workout. Over time, the pain worsens and starts to interfere with playing your sport. Eventually, the pain interferes with daily movements such as climbing stairs or rising from a chair.

Jumper’s knee complications

If you try to work through your pain, ignoring your body’s warning signs, you could cause increasingly larger tears in the patellar tendon. Knee pain and reduced function can persist if you don’t tend to the problem, and you may progress to the more serious patellar tendinopathy.

Athletes, clinicians, coaches, and athletic trainers need to understand that the treatment for patellar tendinopathy can be a slow and sometimes frustrating process. There are multiple pitfalls to be aware of, including the failure to control pain. The athlete’s beliefs about pain and pathology may influence the development and management of unresponsive tendinopathies. Because some athletes may have been told that they have weakened tendons due to tears and degeneration, and hence an increased risk of rupture, they may develop fear-avoidance behavior, which can be associated with poorer functional outcomes in individuals suffering from lower-limb tendinopathy. Over-reliance on non-invasive therapies like shockwave therapy and injections instead of including rehabilitation exercises as part of the treatment plan can also lead to complications. Failure to address the athletes landing kinematics can also bring difficulties. Athletes should have their jump-landing mechanics retrained after adequate rehabilitation ¹³⁾.

Jumper’s knee diagnosis

During the exam, your doctor may apply pressure to parts of your knee to determine where you hurt. Usually, pain from patellar tendinitis is on the front part of your knee, just below your kneecap.

Imaging tests

Your doctor may suggest one or more of the following imaging tests:

• X-rays. X-rays help to exclude other bone problems that can cause knee pain.
• Ultrasound. This test uses sound waves to create an image of your knee, revealing tears in your patellar tendon.
• Magnetic resonance imaging (MRI). MRI uses a magnetic field and radio waves to create detailed images that can reveal subtle changes in the patellar tendon.

Jumper’s knee treatment

There is no evidence-based, preferred treatment of choice for jumper’s knee. Doctors typically begin with less invasive treatments before considering other options, such as surgery. Refractory response to treatment is also typical for jumper’s knee which often leaves the health professional and patients searching for alternative therapies ¹⁴⁾.

Most patients with jumper’s knee are managed through medical and rehabilitative treatment in the initial stages of the disease ¹⁵⁾. Early recognition and diagnosis of jumper’s knee are vital as it can have a progressive course. Pain relievers such as ibuprofen (Advil, Motrin IB, others) or naproxen sodium (Aleve, others) may provide short-term relief from pain associated with jumper’s knee. Although non-steroidal anti-inflammatory drugs (NSAIDs) were used traditionally, these have recently become less judicious as more physicians come to realize that jumper’s knee is not inflammatory. Hence, NSAIDs may not provide significant long-term benefit in jumper’s knee tendinopathy ¹⁶⁾.

Home remedies

If your knee hurts, consider the following:

• Pain relievers. Over-the-counter medications such as ibuprofen and naproxen sodium may provide short-term pain relief.
• Avoid activity that causes pain. You may need to practice your sport less often or temporarily switch to a lower impact sport. Working through pain can further damage your patellar tendon.
• Ice. Apply ice after activity that causes pain. Place ice in a plastic bag and wrap the bag in a towel. Or try an ice massage. Freeze water in a plastic foam cup and hold the cup as you apply the ice directly to your skin.
• Braces. These are sometimes recommended to provide support for the knee. There is no clear evidence if there is a benefit, but it does provide some patients with relief from their symptoms.

Physical therapy

A variety of physical therapy techniques can help reduce the symptoms associated with jumper’s knee, including:

• Stretching exercises. Regular, steady stretching exercises can reduce muscle spasm and help lengthen the muscle-tendon unit. Don’t bounce during your stretch.
• Strengthening exercises. Weak thigh muscles contribute to the strain on your patellar tendon. Exercises that involve lowering your leg very slowly after extending it can be particularly helpful, as can exercises that strengthen all of the leg muscles in combination, such as a leg press.
• Patellar tendon strap. A strap that applies pressure to your patellar tendon can help to distribute force away from the tendon and direct it through the strap instead. This may help relieve pain.
• Iontophoresis. This therapy involves spreading a corticosteroid medicine on your skin and then using a device that delivers a low electrical charge to push the medication through your skin.

Eccentric training has been suggested to play a key role in the rehabilitation of jumper’s knee ¹⁷⁾. According to Rodriguez-Merchan ¹⁸⁾ eccentric training appears to be the treatment of choice for patients suffering from patellar tendinopathy. Athletes must avoid activities such as excessive jumping or impact loading of the knee which only aggravate the situation. As the pain begins to subside, the intensity of rehabilitation therapy and sport-specific training can be slowly increased ¹⁹⁾.

Other procedures

Given the refractory response to many initial treatments, new methods have recently emerged. These include dry-needling, sclerosing injections, platelet-rich plasma therapy, extracorporeal shock wave treatment and hyperthermia thermotherapy ²⁰⁾.

If conservative treatments don’t help, your doctor may suggest other therapies, such as:

• Corticosteroid injection. An ultrasound-guided corticosteroid injection into the sheath around the patellar tendon may help relieve pain. But these types of drugs can also weaken tendons and make them more likely to rupture.
• Platelet-rich plasma injection. This type of injection has been tried in some people with chronic patellar tendon problems. Studies are ongoing. It is hoped the injections might promote new tissue formation and help heal tendon damage.
• Oscillating needle procedure. This outpatient procedure is performed using local anesthesia. Your doctor uses ultrasound imaging to guide a small oscillating needle that cuts away the damaged area while sparing healthy tendon. This is a relatively new procedure, but results have shown promise.

Surgical treatment

Surgery usually remains the last resort for chronic refractory cases. Traditionally, the gold standard for surgical treatment of patellar tendinopathy involved open debridement of the inferior pole of the patella, as well as debridement of the patella tendon. Recently, knee arthroscopy has gained popularity for tissue debridement and release ²¹⁾.

Jumper’s knee prognosis

Most cases of jumper’s knee will resolve with nonoperative management ²²⁾. Nevertheless, mild to moderate pain may persist for 15 years in adult athletes with jumper’s knee but does not appear to limit leisure-time physical activity ²³⁾.

Rudavsky and Cook ²⁴⁾ say that the process of returning to sports play is slow. This process is often dependent on a variety of factors ranging from the severity of pain, grade of dysfunction, the sport practiced, the quality of rehabilitation, the athlete’s performance level, and the presence of intrinsic and extrinsic factors. A previous study ²⁵⁾ that used imaging technology to classify the severity of the lesion said that mild pathologies might take anywhere from 20 days for the patient to return to sport, whereas more severe cases might take 90 days. Other experts mention that athletes with severe dysfunction might need anywhere from 6 to 12 months to recover. Lang and coworkers published a study were they analyzed patients who were treated surgically (arthroscopic patellar release). They determined that the meantime to return to play was 4.03 plus or minus 3.18 months ²⁶⁾.

Joshua et al. ²⁷⁾ performed a systemic search of previous studies to compare the efficacy of treatment for commonly used invasive and non-invasive treatment options. The conclusion reached was that eccentric squat-based therapy, shockwave, or platelet-rich plasma could be used as monotherapies or as adjunct therapies to accelerate recovery. Surgery or shockwave can be considered for patients who fail to improve after six months of conservative treatment. Since jumper’s knee is not inflammatory, corticosteroid injections should not be used ²⁸⁾.

Patellar tendinopathy may cause long-lasting symptoms that can lead to the athlete’s early retirement from sport. In a small prospective case-control study, Kettunen et al. ²⁹⁾ found that 53% of their symptomatic subjects with jumper’s knee had quit their sport when compared to their asymptomatic counterpart in which only 7% quit.

Oral allergy syndrome

Oral allergy syndrome also called “pollen-food allergy syndrome” ¹⁾, “pollen-associated food allergy syndrome” ²⁾, “birch pollen-related food allergy” ³⁾, is a type of contact food allergic reaction brought about by contact of the mouth and throat with flavors, nuts, raw fruits, and vegetables ⁴⁾. Some experts suggest that oral allergy syndrome may be a collection of symptoms resulting from pollen-food syndrome or another food allergy ⁵⁾. Oral allergy syndrome is an allergic reaction to fruits and vegetables that have similar proteins to certain pollens. The most well-known symptoms include itchiness or swelling of the mouth, face, lips, tongue and throat, which starts rapidly after a raw fruit or vegetable is placed in the mouth, and that, as a rule, continues for just a couple of minutes after the food has been swallowed. Although in rare cases, the reaction can occur more than an hour later. Moreover, other foods have been implicated, such as legumes and nuts, and symptoms may persist beyond the oral cavity ⁶⁾. Itching, tingling, and/or swelling of the lips, tongue, palate, or throat are typical ⁷⁾ and, although considered rare, severe reactions have also been reported, including anaphylaxis ⁸⁾.

The oral allergy syndrome is a remarkably common sign of food allergy, mainly in adults who are allergic to tree pollen ⁹⁾. Oral allergy syndrome includes oral itching, lip swelling, and laryngeal angioedema after contact with allergenic foods ¹⁰⁾. Infrequently, oral allergy syndrome may trigger severe swelling of the throat that causes difficulty swallowing and/or breathing. Anaphylaxis may be initiated by a pollen cross-reactive raw vegetable or fruit; nevertheless, this occurrence is extremely infrequent ¹¹⁾. Patients who have oral signs seem to show that the capacity exists for advancement to a further systemic reaction, and restriction of the diet would be correctly advised. Heating food does not change the allergic capability of those specific food allergens ¹²⁾.

Foods that may cause oral allergy syndrome:

• Apple, Apricot, Carrot, Celery, Cherry, Kiwi, Peach, Pear, Plum, Almond and Hazelnut
• Cantaloupe, Honeydew, Orange, Tomato, Watermelon
• Banana, Cantaloupe, Carrot, Celery, Cucumber, Honeydew, Peach, Watermelon, Zucchini

Pollen allergy:

• Spring tree pollen: Birch
• Summer grass pollen: Timothy and Orchard
• Fall weed pollen: Mugwort and Ragweed

Oral allergy syndrome is generally considered to be a mild form of food allergy. Rarely, oral allergy syndrome can cause severe throat swelling leading to difficulty swallowing or breathing. In a person who is highly allergic, a systemic reaction, called anaphylaxis, may be caused by a pollen cross-reactive raw fruit or vegetable, but this is very uncommon. Oral allergy syndrome can occur at any time of the year.

The frequency of oral allergy syndrome with pollen allergy has been reported as 5-8%; 1-2% of patients with oral allergy syndrome with pollen allergy show extreme responses, e.g., anaphylaxis. Birch tree pollen, ragweed pollen, and grass pollen hypersensitivity cause the symptoms.

Although there is no definitive test for oral allergy syndrome, affected individuals often have a positive allergy skin test result triggered by the food’s fresh extract or blood test for specific pollen, along with a history of symptoms after ingestion of the suspected foods. Oral challenge result is normally positive with the raw food and negative with the similar cooked food.

In the pediatric population, oral allergy syndrome is predominantly found in adolescent populations ¹³⁾; oral allergy syndrome is more characteristic in patients with seasonal allergic rhinitis ¹⁴⁾. Ma et al ¹⁵⁾ revealed that the frequency of oral allergy syndrome in patients with pollen allergy was 5–8%; 20% of allergists reported that a small number of patients show advanced systemic reactions; 30% of allergists never recommended epinephrine for oral allergy syndrome, and 3% routinely did recommend epinephrine when necessary.

Oral allergy syndrome treatment include:

• Avoiding raw-foods that cross react with your pollen allergens.
• Taking oral antihistamines medications to relieve mild symptoms.
• Bake or cook foods to degrade the proteins and eliminate the cross reaction.
• Eat canned fruits or vegetables during your pollen season
• Peel the fruit, as the protein is often concentrated in the skin

See your allergist when the oral allergy syndrome symptoms get worse or occur when eating nuts.

Oral allergy syndrome causes

Oral allergy syndrome is brought about by food allergens; for the most part, these are “uncooked fruits and raw vegetables” that contact the patient’s oropharynx ¹⁶⁾. The allergic foods that trigger oral allergy syndrome are effectively inactivated by the corrosive action of the stomach, so the response typically ends when the food is swallowed. Thus, as a result, oral allergy syndrome seldom causes serious or life-endangering responses. Cooking or warming additionally attenuates the allergens, so cooked or canned foods seldom trigger oral allergy syndrome symptoms ¹⁷⁾.

Certain customary samples of foods that trigger oral allergy syndrome are recorded, alongside the kind of pollen that is identified with these foods ¹⁸⁾:

• Birch tree pollen hypersensitivity. The patients may experience oral symptoms after the ingestion of apricot, peach, apple, carrot, almond, plum, hazelnut, pear, celery, fennel, parsley, aniseed, coriander, soybean, caraway, or peanut ¹⁹⁾. Birch allergy can often be related to oral allergy syndrome. Betv1 is the chief birch allergen ²⁰⁾.
• Ragweed-pollen hypersensitivity. The patients may experience oral symptoms after eating banana, melon, cucumber, or kiwi ²¹⁾.
• Grass-pollen hypersensitivity. The patients may be used to perioral and oral symptoms and signs after the ingestion of orange, tomato, melon, or peanut. Also, irritated and red hands may be observed after peeling raw potato ²²⁾. Oral allergy syndrome develops in individuals with pollen allergy. Allergens in raw vegetables, fruits, and nuts resemble the pollen allergens ²³⁾.

Even though numerous foods are recorded for each of the pollens mentioned above, many patients with oral allergy syndrome respond to only one or few of these foods ²⁴⁾.

Oral allergy syndrome pathophysiology

In oral allergy syndrome, typical signs are associated with contact to food antigens and IgE-induced release of mediators. With regard to food intolerance that does not produce a positive radioallergosorbent test or skin test result, it seems appropriate to think about non–IgE-mediated causes ²⁵⁾. Oral allergy syndrome is sometimes accompanied by a systemic reaction and is considered to be an IgE-mediated allergy ²⁶⁾. Experimental reports emphasized particular elements that prevent improvement in oral tolerance that may similarly be involved in humans. Such elements include the apoptosis of T cells that are antigen specific, paralysis of the T cells, and deficiency in generation of T cells that are regulatory ²⁷⁾.

The interferon γ cytokine is also encoded in humans ²⁸⁾. In fetal life, the T-helper (Th) type 2 cell cytokine pattern prevails. This predominance may prevent harm to the placenta by Th1 cells. If the Th2 profile persists after delivery, then this would contribute to the absence of development of oral tolerance ²⁹⁾. Microbial life is established in the gut quickly after delivery, which creates a strong provocation to shifting toward a Th1 cell-mediated response ³⁰⁾. The so-called hygiene theory proposes avoiding antibacterial treatment that might itself be responsible for the expansion in allergy ³¹⁾. Another essential component is the specific variation in IgE-mediated reaction. For example, a polymorphism in the CD14 gene is related to food allergy and elevated amounts of IgE ³²⁾. Furthermore, T-cell immuno-globulin mucin-1 (TIM-1) encoded by atopy susceptibility gene (Havcrl) is related to the control of Th1 and Th2 immune reactions. The evidence of a relationship between atopy and TIM-1 seems to show another application of the hygiene hypothesis ³³⁾.

Oral allergy syndrome symptoms

Oral allergy syndrome symptoms occur immediately after eating certain raw fruits, vegetables, or nuts and are usually limited to the mouth and throat. The most common symptoms include: itching or swelling of the mouth, lip, tongue, or throat. Paraesthesia; angioedema of the oral mucosa, tongue, palate, and oropharynx angioedema; and voice hoarseness can be seen. Oral allergy syndrome occurs in 47–70% of patients with pollen allergy ³⁴⁾. Oral allergy syndrome is an immunoglobulin E (IgE) mediated allergic response. Homologous proteins and cross-responding antigenic determinants in pollens and in different vegetables and fruits may initiate the symptoms ³⁵⁾. Patients with sensitivity to birch antigens frequently have a response to “crisp apple, celery, cherry, hazelnuts, and carrot,” whereas patients sensitized to ragweed may respond to “melons, kiwi, and banana” ³⁶⁾. Symptoms are generally localized to the oropharynx and oral mucosal manifestations; throat pruritus or angioedema may occur ³⁷⁾. oral allergy syndrome symptoms may worsen during pollen seasons. Most patients with oral allergy syndrome are able to tolerate cooked, processed and peeled forms of these foods.

The main symptoms of oral allergy syndrome are itching and mild swelling of the lips, mouth, and throat ³⁸⁾. More unusual symptoms are the ones that do not affect the mouth and throat, such as itching, slight swelling or redness of the hands, nausea or stomach irritation (10%), vomiting, diarrhea, chest tightness, or loss of consciousness ³⁹⁾. Manifestations of oral allergy syndrome may vary according to the pollen season. Symptoms are typically most evident during the associated pollen season and for a few months afterward. Likewise, oral allergy syndrome symptoms might be particular to one fruit ⁴⁰⁾.

All individuals with oral allergy syndrome have a pollen allergy. Pollen allergy causes nasal symptoms (watery nasal discharge, nasal obstruction, sneezing, itching), eye symptoms (itching and swelling around the eyes), throat and ear symptoms (sore throat, voice changes, tingling in the ears), and sleep problems (frequent arousing, daytime fatigue) that happen at the same period every year ⁴¹⁾.

Allergic manifestations are usually limited to the oropharyngeal region, such as swelling of the lips, tongue, and throat. Approximately 9% of individuals have symptoms at the oropharynx, and 1–2% of individuals with oral allergy syndrome present with severe responses, e.g., angioedema and anaphylaxis ⁴²⁾. The response is created via “heat-labile food proteins,” which cause cross-reactivity via the pollen proteins that cause allergy ⁴³⁾. Those reactions usually occur in individuals exposed to “birch-tree dust” after ingestion of “crude apples, fruits, potatoes, hazelnuts, carrots, and kiwis.” In addition, individuals allergic to “ragweed” respond to “banana and crisp melons” ⁴⁴⁾.

Oral allergy syndrome is typically diagnosed from responses to vegetables and fruits. oral allergy syndrome is sometimes inappropriately used when mild oral symptoms are actually pointing to seriously allergic responses to foods (i.e., shellfish or nuts) ⁴⁵⁾. In the study by Ma et al ⁴⁶⁾ about the prescribing habits of allergists for a child with nut sensitivity, 13% gave a conclusion of oral allergy syndrome and 25% did not count epinephrine. Similarly, 20% reported that they used the term oral allergy syndrome for systemic manifestations brought on by fruit ⁴⁷⁾.

Oral allergy syndrome used to be thought to be a self-limiting phenomenon related to ingestion of raw protein ⁴⁸⁾. Silviu-Dan and Melanson ⁴⁹⁾ evaluated 26 patients with oral allergy syndrome to decide the risk of anaphylaxis separately from the oropharyngeal difficulties that occur after eating the specific protein. Six of the patients had extreme anaphylactic responses that required acute treatment ⁵⁰⁾. Patients with oral allergy syndrome who had anaphylaxis had the same likelihood of allergic rhinitis or asthma as patients with oral allergy syndrome without anaphylaxis ⁵¹⁾.

Mild symptoms from eating nuts may indicate a more severe food allergy with a risk of anaphylaxis. See an allergist if you have symptoms after eating nuts.

Risk factors for anaphylactic responses are:

• having a systemic response to the food,
• responding to the cooked form of the food,
• skin-prick test positivity to the food extract,
• lack of sensitization to the associated pollen,
• allergy to peach ⁵²⁾.

When fruit allergy develops without pollen allergy, responses will probably be extreme ⁵³⁾. In one review, 82% of the patients with food allergy and without allergic rhinitis showed systemic responses, (i.e., 36% experienced anaphylaxis); conversely, 45% of patients with allergic rhinitis had systemic responses and 9% experienced anaphylactic reactions ⁵⁴⁾.

Oral allergy syndrome diagnosis

The diagnosis of oral allergy syndrome is undertaken by clinical history and by skin-prick test positivity with fresh food extracts. The oral challenge result is positive with the raw food and negative with the cooked food ⁵⁵⁾. Assessment of an individual with pollen-food allergy syndrome should incorporate a careful medical history to decide which foods trigger the symptoms and are responsible for the responses, tests that may incorporate skin-prick test with fresh or raw fruits, and possibly oral food challenges. If there is a systemic response and diagnostic laboratory data, the food ought to be prevented, and epinephrine should be prescribed. Assessment for other associated foods ought to be undertaken ⁵⁶⁾.

The diagnostic exactness of skin-prick test with artificial extracts is highly variable. Now and again, skin-prick tests that use the food in its common form are more trustworthy, particularly for plant food allergy ⁵⁷⁾. The indicative value of the specific IgE depends on the concentrate used ⁵⁸⁾. Skin-prick tests give prompt outcomes that permit a straightforward clinical assessment and are less expensive than in vitro techniques. Because of cross-reactivity, both strategies may give false positivity. For example, patients oversensitive to grass pollen ordinarily have IgE-specific reactions to oat, however, with no symptoms ⁵⁹⁾. There have been some efforts to relate IgE-antibody levels to double-blind placebo controlled food challenge results. Double-blind placebo controlled food challenge is currently the criterion standard for a definite diagnosis of IgE-mediated allergy ⁶⁰⁾.

Elimination diets

Elimination diets may be valuable in individuals with continuing symptoms. Positive food testing results to skin-prick test and/or radioaller-gosorbent test and cases suspected from the medical history are confirmable. Twenty-one days are typically adequate to cast reliable doubt on food allergy. The outcome is viewed as positive if a steady improvement of the symptoms occur. If the symptoms return once foods are reestablished, a double-blind placebo controlled food challenge should be accomplished ⁶¹⁾.

Double-blind placebo controlled food challenge

The double-blind placebo controlled food challenge is the principal approved test for food allergy diagnosis ⁶²⁾. Because the technique is complicated and has a long duration, the test is restricted to individuals being evaluated for perpetual avoidance of foods fundamental to a healthy diet, e.g., milk, eggs. In patients with past serious food responses, the double-blind placebo controlled food challenge test is contraindicated. The tested food is prepared in opaque capsules, or in its normal shape veiled by an inactive component. The dummy treatment consists of a case of using an item of similar appearance that contains dextrose or other inactive food components that are certain to be tolerated by the individual and permit satisfactory concealment of the administered food ⁶³⁾.

Food patch test

Food patch tests were, until recently, in use for the analysis of food allergy, including delayed signs. For pediatric patients who experience atopic dermatitis, including delayed responses, a food patch test improves diagnostic accuracy, yet not at the expense of sensitivity or speed ⁶⁴⁾. This technique was not approved for routine diagnosis. Despite the fact that numerous reports support the usefulness of “lymphocytes proliferation and cytokine increment” after exposure to food allergens, there is no affirmation of benefit over the customary analytic method ⁶⁵⁾.

Lactose breath test

Diagnosis of lactose intolerance depends on the peak in breath hydrogen (H2) after lactose intake that is used for the breath-test analysis ⁶⁶⁾.

Cross-reactivity

Allergic cross-reactivity is the situation in which IgE antibodies initially recognized as the epitopes of one allergic reaction are found to cause comparable problems in a further allergy ⁶⁷⁾. More than 65% of food allergens consist of just four basic species: (1) the Bet v1 homologs, (2) the profilins, (3) the cereal prolamin superfamily, and (4) the cupins ⁶⁸⁾. This might indicate broad IgE cross-reactivity, even among allergens that occur in systematically distinct plants. Moreover, IgE binding may happen if up to 35–40% of the amino acid sequence is conserved ⁶⁹⁾.

Oral allergy syndrome treatment

There is no “cure” for the oral allergy syndrome ⁷⁰⁾. Food allergy treatment depends on antihistamines, corticosteroids, and epinephrine (intramuscular). No clear evidence exists for using sodium cromoglycate ⁷¹⁾. “Specific immune therapy” for food allergy is not feasible. Specific immune therapy that used peanuts was discontinued because of excessively high levels adverse effects ⁷²⁾. Novel encouraging immunologic investigations of mice include the utilization of recombinant allergens and the use of the allergen mixed with heat killed listeria as an adjuvant ⁷³⁾.

Monoclonal humanized antibodies of anti-IgE may be used to counter severe food allergy. IgE receptor antibodies of the mast cells that lack cell degranulation might obstruct the allergic response. Initial studies demonstrate that anti-IgE treatment can, in essence, enlarge the threshold amount of peanut protein necessary to incite allergic symptoms in individuals with peanut allergy ⁷⁴⁾. The utilization of anti-IgE treatment in combination with specific immune therapy might be a valuable therapy in the future ⁷⁵⁾.

Although serious responses are rarely encountered, intramuscular use of an epinephrine autoinjector (e.g., EpiPen, Epinephrine Auto-injector) may be advised ⁷⁶⁾. Food allergy-induced asthma encompassed 9.5% of individuals and asthma that occurred singly was recognized in just 2.8% of patients. Food allergy-induced asthma is potentially life threatening, which leads to prescribing epinephrine autoinjectors and bronchodilators ⁷⁷⁾.

Oral allergy syndrome diet

Some people report symptoms with only one food and others with many different fruits and vegetables. Some people report that only certain varieties of the fruit cause symptoms, for example specific apple varieties. In the case of oral allergy syndrome, individuals react to different foods based on what type of seasonal allergies they are affected by. For instance, if you are allergic to birch tree pollen, a primary airborne allergen responsible for symptoms in the springtime, you may have reactions triggered by pitted fruit or carrot. Even peanuts, almond, and hazelnut may cause mouth itching in those with birch pollen allergy. If mouth itching is noted with nuts, you should see an allergist /immunologist because mild mouth symptoms may signal a more serious allergic reaction to nuts. People with allergies to grasses may have a reaction to peaches, celery, tomatoes, melons (cantaloupe, watermelon and honeydew) and oranges. Those with reactions to ragweed might have symptoms when eating foods such as banana, cucumber, melon, and zucchini. This convenient table lists the possible pollen and plant food cross-reactivities.

If you have symptoms of oral allergy syndrome, avoid eating these raw foods, especially during allergy season because in many patients, oral allergy syndrome worsens during the pollen season of the pollen in question. One way to reduce cross-reactions with food is to bake or microwave the food because high temperatures break down the proteins responsible for oral allergy syndrome. Eating canned food may also limit the reaction. And, peeling the food before eating may be helpful, as the offending protein is often concentrated in the skin.

Figure 1. Oral allergy syndrome food list