NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: 2q37 microdeletion syndrome is characterized by mild-moderate developmental delay/intellectual disability, brachymetaphalangy of digits 3-5 (often digit 4 alone) (>50%), short stature, obesity, hypotonia, characteristic facial appearance, autism or autism spectrum disorder (30%), joint hypermobility/dislocation, and scoliosis. Other findings include seizures (20%-35%), congenital heart disease, CNS abnormalities (hydrocephalus, dilated ventricles), umbilical/inguinal hernia, tracheomalacia, situs abnormalities, gastrointestinal abnormalities, and renal malformations. Wilms tumor has been reported in two individuals.

Diagnosis/testing: Chromosome analysis confirms the diagnosis of 2q37 deletion syndrome in 80%-85% of affected individuals. In about 15%-20% of cases the small size of the deleted region can only be detected using deletion analysis (which relies on a variety of methods). In some individuals, 2q37 microdeletion syndrome results from chromosome rearrangements involving 2q37 (e.g., chromosome 2 inversion, ring chromosome 2, or translocation between chromosome 2 and another chromosome). Mutation of HDAC4 has been proposed as causative for most of the features of the 2q37 microdeletion syndrome. Several affected individuals without microdeletions had inactivating mutation of HDAC4, a gene in the 2q37 deleted region, leading to the proposal that mutation of this gene may be causative for most of the features of the 2q37 microdeletion syndrome.

Management: Treatment of manifestations: Multidisciplinary care by specialists in the following fields is often required: clinical genetics, speech pathology, occupational and physical therapy, child development, neurology, cardiology, gastroenterology, nutrition/feeding, ophthalmology, and audiology. Infants benefit from enrollment in an early-intervention program; most school-age children benefit from an individualized educational program (IEP).

Surveillance: Ongoing routine primary care; periodic reevaluation by a clinical geneticist to provide new recommendations and information about the syndrome; periodic neurodevelopmental and/or developmental/behavioral pediatric evaluation to assist in the management of cognitive and behavioral problems. Screening for renal cysts at age four years and again at puberty is suggested. For young children with a deletion that includes 2q37.1, screening for Wilms tumor can be considered.

Evaluation of relatives at risk: It is reasonable to perform genetic testing of any young child at risk, so that Wilms tumor surveillance can be considered in those with a deletion that includes 2q37.1.

Genetic counseling: Most individuals with the 2q37 microdeletion syndrome have a de novo chromosome deletion and their parents have normal karyotypes. In approximately 5% of published cases, probands have inherited the deletion from a parent who is a balanced translocation carrier. The risk to sibs of a proband depends on the chromosome findings in the parents: the recurrence risk for future pregnancies is negligible when parental karyotypes are normal; if a parent has a balanced structural chromosome rearrangement, the risk to sibs is increased and depends on the specific chromosome rearrangement. Regarding risks to offspring: no individual with a cytogenetically visible 2q37 deletion is known to have reproduced; however, it is reasonable to expect normal fertility in mildly affected individuals with the 2q37 microdeletion syndrome. Prenatal diagnosis for pregnancies at increased risk is possible. Deletion or mutation of HDAC4 may be inherited in an autosomal dominant manner but is more commonly de novo.