Mosaic variegated aneuploidy syndrome

Title

Other Names:

MVA syndrome; Warburton-Anyane-Yeboa syndrome

Categories:

Congenital and Genetic Diseases; Rare Cancers

Summary Summary

Mosaic variegated aneuploidy (MVA) syndrome is a very rare condition characterized by problems with cell division (specifically during mitosis) that results in a high number of cells with missing (monosomy) or extra (trisomy) genetic material in multiple chromosomes and tissues (mosaic aneuploidies).^[1]^[2] Only about 50 cases have been described in the medical literature.^[1]^[3] Features include severe microcephaly, growth deficiency and short stature, mild physical abnormalities, eye abnormalities, problems with the brain and central nervous system, seizures, developmental delay, and intellectual disability. The risk for cancer is increased, with rhabdomyosarcoma, Wilm's tumor, and leukemia reported in several cases.^[1]^[3]^[4]

MVA syndrome is an autosomal recessive condition. It can be caused by changes (mutations) in the BUB1B gene or the CEP57 gene. The BUB1B gene encodes BubR1, a key protein in mitotic spindle checkpoint function. The CEP57 gene is involved in microtubule stabilization. Both play a role in the process of cell division.^[1]^[5] Treatment depends on the symptoms present in each person, but may include growth hormone therapy. Individuals with a BUB1B mutations should also be offered cancer screening.^[1]

Last updated: 3/2/2017

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Ascites	Very frequent (present in 80%-99% of cases)
Cataract	Very frequent (present in 80%-99% of cases)
Corneal opacity	Very frequent (present in 80%-99% of cases)
Dandy-Walker malformation	Very frequent (present in 80%-99% of cases)
Epicanthus	Very frequent (present in 80%-99% of cases)
Glaucoma	Very frequent (present in 80%-99% of cases)
Increased nuchal translucency	Very frequent (present in 80%-99% of cases)
Micrognathia	Very frequent (present in 80%-99% of cases)
Microphthalmia	Very frequent (present in 80%-99% of cases)
Muscular dystrophy	Very frequent (present in 80%-99% of cases)
Polyhydramnios	Very frequent (present in 80%-99% of cases)
Abnormality of vision	Frequent (present in 30%-79% of cases)
Intellectual disability	Frequent (present in 30%-79% of cases)
Microcephaly	Frequent (present in 30%-79% of cases)
Triangular face	Frequent (present in 30%-79% of cases)
Abnormal lung lobation	Occasional (present in 5%-29% of cases)
Abnormality of immune system physiology	Occasional (present in 5%-29% of cases)
Abnormality of skin pigmentation	Occasional (present in 5%-29% of cases)
Acute lymphoblastic leukemia	Occasional (present in 5%-29% of cases)
Aortic regurgitation	Occasional (present in 5%-29% of cases)
Aplasia/Hypoplasia of the cerebellum	Occasional (present in 5%-29% of cases)
Aplasia/Hypoplasia of the corpus callosum	Occasional (present in 5%-29% of cases)
Apnea	Occasional (present in 5%-29% of cases)
Atrial septal defect	Occasional (present in 5%-29% of cases)
Clinodactyly of the 5th finger	Occasional (present in 5%-29% of cases)
Coarctation of aorta	Occasional (present in 5%-29% of cases)
Colon cancer	Occasional (present in 5%-29% of cases)
Depressed nasal ridge	Occasional (present in 5%-29% of cases)
Downslanted palpebral fissures	Occasional (present in 5%-29% of cases)
Duodenal atresia	Occasional (present in 5%-29% of cases)
Frontal bossing	Occasional (present in 5%-29% of cases)
Hearing impairment	Occasional (present in 5%-29% of cases)
High forehead	Occasional (present in 5%-29% of cases)
Holoprosencephaly	Occasional (present in 5%-29% of cases)
Hypothyroidism	Occasional (present in 5%-29% of cases)
Intestinal polyposis	Occasional (present in 5%-29% of cases)
Intrauterine growth retardation	Occasional (present in 5%-29% of cases)
Low-set, posteriorly rotated ears	Occasional (present in 5%-29% of cases)
Multicystic kidney dysplasia	Occasional (present in 5%-29% of cases)
Multiple cafe-au-lait spots	Occasional (present in 5%-29% of cases)
Muscular hypotonia	Occasional (present in 5%-29% of cases)
Myelodysplasia	Occasional (present in 5%-29% of cases)
Nephroblastoma	Occasional (present in 5%-29% of cases)
Osteolysis	Occasional (present in 5%-29% of cases)
Rhabdomyosarcoma	Occasional (present in 5%-29% of cases)
Seizures	Occasional (present in 5%-29% of cases)
Short palpebral fissure	Occasional (present in 5%-29% of cases)
Sloping forehead	Occasional (present in 5%-29% of cases)
Stomach cancer	Occasional (present in 5%-29% of cases)
Subaortic stenosis	Occasional (present in 5%-29% of cases)
Vaginal neoplasm	Occasional (present in 5%-29% of cases)
Wide nose	Occasional (present in 5%-29% of cases)
Blepharophimosis	Very rare (present in 1%-4% of cases)
Cafe-au-lait spot	Very rare (present in 1%-4% of cases)
Deeply set eye	Very rare (present in 1%-4% of cases)
Delayed skeletal maturation	Very rare (present in 1%-4% of cases)
Dolichocephaly	Very rare (present in 1%-4% of cases)
Growth hormone deficiency	Very rare (present in 1%-4% of cases)
Intellectual disability, mild	Very rare (present in 1%-4% of cases)
Long face	Very rare (present in 1%-4% of cases)
Low-set ears	Very rare (present in 1%-4% of cases)
Short nose	Very rare (present in 1%-4% of cases)
Sleep apnea	Very rare (present in 1%-4% of cases)
Agenesis of corpus callosum	-
Anteverted nares	-
Autosomal recessive inheritance	-
Bifid scrotum	-
Brachycephaly	-
Cerebellar hypoplasia	-
Cerebral hypoplasia	-
Clinodactyly	-
Combined immunodeficiency	-
Cryptorchidism	-
Feeding difficulties in infancy	-
Generalized hypotonia	-
Generalized myoclonic seizures	-
Generalized tonic-clonic seizures	-
Hydrocephalus	-
Hypertelorism	-
Hypodysplasia of the corpus callosum	-
Hypospadias	-
Intellectual disability, profound	-
Leukemia	-
Long philtrum	-
Malar flattening	-
Micropenis	-
Midface retrusion	-
Nystagmus	-
Oligohydramnios	-
Phenotypic variability	-
Posteriorly rotated ears	-
Postnatal growth retardation	-
Premature chromatid separation	-
Renal cyst	-
Severe global developmental delay	-
Short neck	-
Short sternum	-
Small for gestational age	-
Triangular mouth	-
Upslanted palpebral fissure	-
Ventricular septal defect	-
Ventriculomegaly	-

Last updated: 9/1/2017

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Do you have updated information on this condition? Let us know.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Mosaic variegated aneuploidy syndrome 1
Mosaic variegated aneuploidy syndrome 2
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Mosaic variegated aneuploidy syndrome. Click on the link to view a sample search on this topic.

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References References

Hanks S, Rahman N, Snape K. Mosaic variegated aneuploidy syndrome. Orphanet. May 2012; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1052.
Cho CH, Oh MJ, Lim CS, Lee CK, Cho Y, Yoon SY. A case report of a fetus with mosaic autosomal variegated aneuploidies and literature review. Ann Clin Lab Sci. 2015 Winter; 45(1):106-9. https://www.ncbi.nlm.nih.gov/pubmed/25696020.
Mosaic variegated aneuploidy syndrome 1. Online Mendelian Inheritance in Man. April 2, 2012; https://www.omim.org/entry/257300.
Akasaka N, Tohyama J, Ogawa A, Takachi T, Watanabe A, Asami K. Refractory infantile spasms associated with mosaic variegated aneuploidy syndrome. Pediatr Neurol. 2013 Nov; 49(5):364-7. https://www.ncbi.nlm.nih.gov/pubmed/23916859.
Pinson L, Mannini L, Willems M, Cucco F, Sirvent N, Frebourg T, Quarantotti V, Collet C, Schneider A, Sarda P, Geneviève D, Puechberty J, Lefort G, Musio A. CEP57 mutation in a girl with mosaic variegated aneuploidy syndrome. Am J Med Genet A. 2014 Jan; 164A(1):177-81. https://www.ncbi.nlm.nih.gov/pubmed/24259107.