What is Brain Mosaicism And How Does It Affect A Child?

Certain mutations affect only a fraction of a child's cells. They are called mosaic mutations, and they open a new avenue for research on the autism spectrum.

It is understood that the brain starts to form in the womb when the cells develop, divide and copy chromosomes. Sometimes, however, chromosomes are not evenly distributed or completely copied when the cells divide; it can cause 'aneuploidy', as well as other genomic changes, explains Dr N Varsha Monica Reddy, consultant pediatric neurologist at Yashoda Hospitals Hyderabad. She adds that 'mosaicism' means that a person has a 'mixture of cells' that have 'different genetic information'. Mosaicism can occur in the cells in one part of the body -- in the egg or the sperm -- or in a generalised way throughout all cells.

Know Your Genes

The doctor goes on to explain that human bodies are made up of billions of cells, each containing a 'complete copy' of genetic information or DNA. "In all the cells, our genes are found in chromosomes. Genes send messages to the cell to make proteins. There are typically 46 chromosomes that come in 23 pairs. Twenty-two of these chromosome pairs are numbered and known as the 'autosomal chromosomes'. The 23rd pair is made up of the chromosomes X and Y: males have an X and Y chromosome; females have two copies of the X chromosome," Dr Varsha explains.

What Happens During Mosaicism?

According to the doctor, it is possible that a gene variant that would have an impact on brain development is found in the blood of a person who does not show any signs of the condition. "For example, this may mean the blood cells contain the gene variant, but the brain cells contain only the working copy of the gene. This person, thus, has a mixture of cells (mosaic) in their body. Some cells contain the variation in the gene so that it does not work (blood cells) and some have the working gene copy (brain cells). Mosaicism may explain why the set of symptoms in people with the same genetic condition are different, or differ in severity," she says.

What Does It Mean For Children?

The expert says that mosaic gene mutations could explain some cases of autism.

"While scientists have linked autism spectrum disorder to a long list of genes, most children with autism have no known explanation.

"Two new studies, however, implicate mutations that affect only a fraction of a child's cells. Called mosaic mutations, they open a new avenue for research and could eventually become part of diagnostic testing for children on the autism spectrum. Unlike mutations passed down from a parent, mosaic mutations arise after conception. A mutation in a stem cell is passed only to the cells that descend from it. This produces a 'mosaic' pattern. The earlier a mutation happens, the more cells ultimately carry it, sometimes including cells in the brain," says the doctor.

She adds that hemimegalencephaly (HME) and focal cortical dysplasia type II (FCD2) are two malformations of cortical development (MCD) where the involvement of mosaic post-zygotic mutations has been demonstrated. "Both diseases are often associated with medically-refractory epilepsy and require surgical resection."