2q37 deletion syndrome

Overview

2q37 deletion syndrome is a rare genetic disorder caused by the deletion of genetic material at the end of the long arm (q) of chromosome 2, specifically at region 2q37. The syndrome affects multiple body systems and is associated with intellectual disability, developmental delays, distinctive facial features, behavioral problems, and skeletal abnormalities. First described in the 1990s, the severity of symptoms can vary depending on the size of the deletion and the genes involved. It is also known as brachydactyly–mental retardation syndrome in some literature, due to the characteristic combination of shortened fingers and cognitive impairment.

Causes

2q37 deletion syndrome is caused by the loss of genetic material at the terminal end of chromosome 2’s long arm. This deletion may range in size and typically includes genes important for brain development, behavior regulation, and bone growth—such as the HDAC4 gene, which is often implicated in the disorder's core features.

The deletion usually occurs de novo (spontaneously) and is not inherited from either parent. However, in some cases, it can be inherited from a parent with a balanced chromosomal rearrangement or mild manifestations of the syndrome. Genetic counseling is recommended for families.

Symptoms

The clinical presentation of 2q37 deletion syndrome is variable but may include:

• Intellectual disability: Typically mild to moderate

• Global developmental delay: Particularly in speech and motor milestones

• Hypotonia: Low muscle tone in infancy and early childhood

• Behavioral issues: Including autism spectrum disorder traits, hyperactivity, aggression, or repetitive behaviors

• Brachydactyly: Shortening of the fingers and toes, especially of the fourth and fifth digits

• Distinctive facial features: Including a broad forehead, flat nasal bridge, thin upper lip, and rounded cheeks

• Obesity or excessive weight gain

• Skeletal anomalies: Such as scoliosis, joint laxity, or short stature

• Seizures: Reported in some individuals

Additional symptoms may include kidney abnormalities, congenital heart defects, or eye/vision problems in a minority of cases.

Diagnosis

Diagnosis of 2q37 deletion syndrome is based on clinical features and confirmed through genetic testing. Common diagnostic tools include:

• Chromosomal microarray analysis (CMA): The preferred method for identifying submicroscopic deletions

• Karyotype analysis: May reveal larger terminal deletions

• FISH (Fluorescence in situ hybridization): Can confirm deletions in known regions of 2q37

• Parental testing: Determines whether the deletion is de novo or inherited

Diagnosis is often made during evaluations for developmental delay, autism features, or unusual physical traits.

Treatment

There is no cure for 2q37 deletion syndrome. Treatment is supportive and focuses on improving developmental outcomes and managing medical or behavioral concerns. A multidisciplinary care team is essential. Key components of treatment include:

• Early intervention: Speech, physical, and occupational therapies

• Special education support: Including IEPs for learning accommodations

• Behavioral and psychological therapy: For managing autism, aggression, or anxiety

• Medical care: For associated conditions like seizures, scoliosis, or cardiac/kidney anomalies

• Nutritional and weight management: To address obesity in affected children

Prognosis

The prognosis for individuals with 2q37 deletion syndrome varies depending on the size of the deletion and associated symptoms. With early and consistent support, many individuals can make developmental progress and participate in school and social activities. Lifespan is usually not significantly reduced unless serious medical complications are present. Lifelong medical and educational support is often necessary to optimize quality of life and promote independence.