Mosaic Down syndrome

About two to four percent of people with Down syndrome (trisomy 21) have mosaic Down syndrome, where only some of the cells in a person’s body have an extra chromosome 21 ¹⁾. Mosaicism is caused by an error in cell division very early in the development of the unborn baby. In mosaic Down syndrome, only some cells have the extra chromosome 21. The rest of the cells have the right number of chromosomes. A person with mosaic Down syndrome typically has 46 chromosomes in some cells, and 47 chromosomes (with the extra chromosome 21) in others. The features and severity in people with mosaic trisomy 21 may vary widely. Mosaic Down syndrome sometimes leads to a milder level of intellectual disability and less obvious physical features of Down syndrome.

What is mosaicism?

Every cell in the human body comes from one initial cell: the fertilized egg, which is also called the zygote. After fertilization, the zygote then proceeds to divide.

As new cells form, the chromosomes duplicate themselves so that the resulting cells have the same number of chromosomes as the original cell. However, mistakes sometimes happen and one cell ends up with a different number of chromosomes. From then on, all cells originating from that cell will have the different chromosomal number, unless another mistake happens. (All like cells originating from a single type of cell is called a cell line ; for example, the skin cell line, the blood cell line, the brain cell line, etc.)

When a person has more than one type of chromosomal makeup, that is called mosaicism, like the mosaic style of art in which a picture is made up of different colors of tiles. In Down syndrome, mosaicism means that some cells of the body have trisomy 21, and some have the typical number of chromosomes.

Mosaicism is a condition in which cells within the same person have a different genetic makeup. This condition can affect any type of cell, including:

• Blood cells
• Egg and sperm cells
• Skin cells.

How many people have mosaic Down syndrome?

• Approximately 1 in 27,000 people are diagnosed with mosaic Down syndrome.
• Approximately 15% of individuals diagnosed with Trisomy 21 Down syndrome are misdiagnosed and actually have mosaic Down syndrome.
• There are many individuals who are never diagnosed with mosaic Down syndrome.

What did I do to cause my child to have mosaic Down syndrome?

Mosaic Down syndrome happens during cell division at and/or after conception. You did nothing to cause this to happen.

Will my mosaic Down syndrome child need special help?

The majority of children with mosaic Down syndrome do experience delays in developmental milestones compared to their typically developing peers. The most prominent delay noted is speech and communication; however delays can be present in all areas of development.

The majority of children with mosaic Down syndrome require special therapy. Your child may have developmental delays with speech, fine and gross motor skills. With the help of Speech, Occupational, and Physical Therapists, your child’s delays can be helped and often he/she will overcome these delays

One noted learning problem is with mathematics. However, many excel in reading and writing. Some children require special education once they reach school age. Most children are “mainstreamed” in regular education classrooms leaving for extra support in academic areas. But, some children with mosaic Down syndrome require no special education at all.

There is no way to determine how your child will be affected. With time, you will be able to see his/her strengths and if there is a delay you will be able to help your child with appropriate teaching and therapy.

What health concerns does a child with mosaic Down syndrome have?

Because children with mosaic Down syndrome have a percentage of affected cells in their body, they can have the same health concerns of a person with Down syndrome. It is important to talk with your doctor about having scheduled Down syndrome health check-ups as described by the Down Syndrome Medical Interest Group.

People with Down syndrome on the whole do not have medical problems that differ from those in the general population. However some medical conditions are over represented. Most of these are treatable disorders which, if undiagnosed, impose an additional but preventable burden of secondary handicap.

The Down Syndrome Medical Interest Group surveillance guidelines have been developed on the basis of available evidence by a group of clinicians with a special interest in Down syndrome. They are updated as new research and audit evidence becomes available. The guidelines purpose is to set out a minimum safe standard of basic medical surveillance which experts consider essential for all those with Down syndrome.

Down Syndrome Medical Interest Group surveillance guidelines:

• cardiac disease
• thyroid
• hearing
• ophthalmic problems
• and the appropriate monitoring of growth.

For the American Academy of Pediatrics guidelines for children with Down Syndrome go here (https://pediatrics.aappublications.org/content/128/2/393.full).

What does the future hold for my child with mosaic Down syndrome?

No one can tell you what your child will grow up to be. People with mosaic Down syndrome can grow up to be just like everyone else. They have jobs, and families, fun and friends. They have the same feelings as anyone and the same ambitions of their peers. Some individuals do go on to college and have careers. This all depends upon the individual’s wants and capabilities. Some individuals do drive cars, and some do not. This depends on the individual’s comfort level with this and their reflexes that are required for driving. Some individuals do live independently and marry. The majority of individuals do not have speech impairments as adults.

If the affected cells are not located in the reproductive organs, individuals with mosaic Down syndrome have a higher likelihood of having children without extra chromosomes.

Mosaic Down syndrome causes

There are two different ways mosaicism can occur ²⁾:

• The initial zygote had three 21st chromosomes, which normally would result in simple trisomy 21, but during the course of cell division one or more cell lines lost one of the 21st chromosomes.
• The initial zygote had two 21st chromosomes, but during the course of cell division one of the 21st chromosomes were duplicated.

It’s possible to determine the origin of mosaicism in individual cases using special DNA markers, but this isn’t done on a regular basis.

Mosaic Down syndrome characteristics

At the present time, there is not much research on the similarities and differences between simple Down syndrome and mosaic Down syndrome ³⁾. One report published in 1991 ⁴⁾ on mental development in Down syndrome mosaicism compared 30 children with mosaic Down syndrome with 30 children with typical Down syndrome. IQ testing showed that the mean IQ of the mosaic group was 12 points higher than the mean of the non-mosaic group. However, some children with typical Down syndrome did score higher on the IQ tests than some of the children with mosaic Down syndrome.

The Department of Human Genetics at the Medical College of Virginia has had an ongoing study project of children with mosaic Down syndrome. In a survey of 45 children with mosaicism, they found that these children did show delayed development compared to their siblings. When 28 of these children with mosaicism were matched up with 28 children with typical Down syndrome for age and gender, the children with mosaicism reached certain motor milestones earlier than children with typical Down syndrome, such as crawling and walking alone. However, the speech development was equally delayed in both groups.

Mosaic Down syndrome diagnosis

The usual way in which mosaic Down syndrome is discovered is through genetic testing of the baby’s blood. Typically, 20 to 25 cells are examined. If some of the cells have trisomy 21 and some don’t, then the diagnosis of mosaicism is made.

However, this blood test can only determine the level of mosaicism in the blood cell line.

While mosaicism can occur in just one cell line (some blood cells have trisomy 21 and the rest don’t), it can also occur across cell lines (skin cells may have trisomy 21 while other cell lines don’t). In the latter case, it may be more difficult to diagnose mosaicism. When mosaicism is suspected but not confirmed through the blood test, other cell types may be tested: skin and bone marrow are most commonly the next cells checked. Because skin cells and brain cells arise from the same type of cell at the beginning of fetal development (ectoderm), many doctors believe that skin cell tests reflect the chromosomal makeup of the brain cells as well.

Mosaic Down syndrome life expectancy

Currently experts have no research that indicates individuals with mosaic Down syndrome will live longer than their peers with Down syndrome. Current research suggests that individuals with Down syndrome live to 55 yrs of age. The oldest living woman with mosaic Down syndrome lived to the age of 83 years old. With the advances of medical development individuals born in this century should have the same life expectancy as those without extra chromosomes. It is important to remember that people do not die from having mosaic Down syndrome, they die because of medical complications surrounding this syndrome.