SNP Shot: Genomic Insights

Mosaic variegated aneuploidy (MVA) syndrome is a rare condition where some of the body's cells have an incorrect number of chromosomes. Instead of the usual 46 chromosomes, these cells have either extra chromosomes (trisomy) or missing chromosomes (monosomy). This chromosomal abnormality is called aneuploidy. In MVA syndrome, some cells are aneuploid while others have the normal number of chromosomes; this is called mosaicism. Typically, at least 25% of an affected person's cells show this abnormal chromosome count. Because the specific chromosomes that are extra or missing vary from cell to cell, the aneuploidy is described as "variegated."

MVA syndrome often leads to slow growth before birth (intrauterine growth restriction). After birth, children with MVA syndrome continue to grow slowly and are typically shorter than average. They also often have a smaller than normal head size (microcephaly). A key feature of MVA syndrome is a higher risk of developing certain childhood cancers. These cancers include rhabdomyosarcoma (a muscle tissue cancer), Wilms tumor (a kidney cancer), and leukemia (a blood cancer).

Less commonly, individuals with MVA syndrome may have eye abnormalities or distinct facial features, such as a wide nasal bridge or low-set ears. Some may also have brain abnormalities, the most common being Dandy-Walker malformation. Intellectual disability, seizures, and other health issues can also occur.

There are at least three different types of MVA syndrome, each caused by a different gene mutation. Type 1 is the most common and exhibits the classic signs and symptoms described above. Type 2 seems to have slightly different symptoms than type 1, but because so few people have been diagnosed, it's hard to define its exact characteristics. Individuals with MVA syndrome type 2 experience slow growth before and after birth, but their head size is usually normal. Some may also have unusually short arms. Unlike type 1, people with MVA syndrome type 2 do not appear to have a higher risk of cancer. Another type of MVA syndrome is characterized by a significantly increased risk of Wilms tumor. Individuals with this form may also display other symptoms typical of MVA syndrome type 1.

Inheritance:

All forms of MVA syndrome are inherited in an autosomal recessive manner. This means that a person must inherit a mutated copy of either the BUB1B, CEP57, or TRIP13 gene from both parents to develop the syndrome. The parents, who each carry one copy of the mutated gene, usually don't show any signs or symptoms of the condition.

Parents of children with MVA syndrome type 1, who carry one mutated copy of the BUB1B gene, may have a related chromosome issue called premature chromatid separation trait. While these individuals have chromosome abnormalities indicating problems with normal chromosome separation during cell division, they typically experience no health problems as a result of this trait.