What is Mosaic Variegated Aneuploidy?

Mosaic variegated aneuploidy is a rare condition that makes a person more likely to develop cancer because of differences in the function of proteins involved in maintaining chromosome integrity. These differences result in abnormal chromosome counts, called aneuploidy, in certain tissues and cells in the body, called mosaicism. Different chromosomes may be involved in different cell types, making it variegated.

Because the condition results from variants in several different genes, leading to differences in DNA content in different tissues of the body, it is variably associated with a number of clinical features that can include growth restriction, small head, intellectual disability, eye abnormalities, seizures, low muscle tone, and/or abnormalities of the skin, kidneys, genitals, heart and gut, among others.

MVA is caused by changes in one of several genes, including BUB1B, CEP57, TRIP13, BUB1, CENATAC, MAD1L1, MAD2L1BP andCEP192. Changes in SMC5 and SLF2 cause a related condition called Atelis syndrome. Genes carry information telling cells in the body how to work. The genes involved in MVA help maintain the structure and integrity of chromosomes when cells divide.

Most people carry two working copies of each of these genes in their cells. One copy is inherited from each parent. A change in the gene that causes it to not work right is called a variant. People with MVA a variant affecting each of the 2 copies of the MVA gene, often because they have inherited an MVA gene variant from each parent.

People with one working copy and one non-working copy of an MVA gene do not seem to share any clinical features.

A doctor may suspect this diagnosis after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members. Read more about genetic counseling and genetic testing.

The diagnosis of this syndrome is done by sequencing the MVA genes to find variants (changes in the genes). This may be done by targeted, whole exome or whole genome sequencing. Both copies of the person’s MVA genes are checked for possible changes.

Genetic testing may not always find a variant that is responsible for the syndrome. A person could still have the syndrome even if no variants in these genes are found. There may be more, undiscovered genes that play a role in the development of this syndrome.

Individuals with MVA have an increased risk of developing embryonic rhabdomyosarcoma and Wilms tumor during childhood. Patients with MVA have also been reported to have myelodysplastic syndrome, leukemia, neuroblastoma, colorectal and gastric cancers, juvenile granulosa tumors of the ovaries and testes, and other benign tumors.

The exact risk for developing these cancers are not known at this time.

Cancer screening involves tests to check for cancer before symptoms occur. The goal is to find cancer at the earliest and most treatable stage. Guidelines for cancer screening are available online. Recommended screenings may change over time as doctors learn more about this syndrome, so these screening tests should be discussed with a health care provider who knows this syndrome well. Other ideas to reduce the risk of cancer include:
  • Eat a healthful diet with lots of fruits and vegetables
  • Get regular exercise
  • Avoid smoking or using tobacco products
  • Avoid secondhand smoke
  • Avoid excess sun exposure and always wear sunscreen, hat, and protective clothing when out in the sun
  • Get medical attention for unusual or ongoing symptoms

Because of the medical concerns related to this syndrome, specialists in the following areas may need to assess a child with Mosaic Variegated Aneuploidy:
  • Neurology
  • Urology
  • Ophthalmology
  • Cardiology
  • Dermatology

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