22q11.2 distal deletion syndrome

Overview

22q11.2 distal deletion syndrome is a rare genetic disorder caused by the deletion of a small segment of genetic material in the distal (farther) region of chromosome 22 at position q11.2. It is distinct from the more common 22q11.2 deletion syndrome (DiGeorge syndrome), as it affects a different part of the chromosome and often results in a different clinical presentation. Individuals with this condition may present with developmental delays, growth abnormalities, congenital anomalies, and learning difficulties. However, the symptoms can vary widely, and some individuals may be mildly affected or asymptomatic.

Causes

The syndrome is caused by a deletion in the distal part of the long arm of chromosome 22, typically spanning several genes. The most commonly deleted region lies beyond the typical DiGeorge/velocardiofacial deletion area. The deletion can be:

• De novo: Occurring spontaneously during early development with no family history (most cases)

• Inherited: Passed from a parent who may be mildly affected or show no signs due to variable expressivity

The loss of genes in the distal 22q11.2 region is believed to disrupt critical developmental processes, leading to the clinical features of the syndrome. The exact severity often depends on the size and gene content of the deletion.

Symptoms

Symptoms vary widely among individuals with 22q11.2 distal deletion syndrome. Some of the more commonly reported features include:

• Global developmental delay or mild intellectual disability

• Speech and language delays

• Autism spectrum disorder (ASD) or social communication challenges

• Hypotonia (low muscle tone), particularly in infancy

• Behavioral and emotional issues such as ADHD, anxiety, or mood instability

• Growth delay or short stature

• Congenital anomalies: Including kidney defects, skeletal abnormalities, or heart defects (less common than in proximal deletions)

• Minor facial differences: Such as a broad nasal bridge, low-set ears, or upslanting palpebral fissures

Some individuals may be entirely asymptomatic and are diagnosed only after genetic testing for a related family member or developmental concern.

Diagnosis

Diagnosis of 22q11.2 distal deletion syndrome requires genetic testing. The process typically includes:

• Chromosomal microarray analysis (CMA): Detects the exact location and size of the deletion

• Fluorescence in situ hybridization (FISH): May be used if targeting a known region

• Parental genetic testing: Determines if the deletion is inherited or occurred de novo

Testing is often prompted by developmental delays, learning difficulties, or the presence of congenital anomalies.

Treatment

There is no cure for 22q11.2 distal deletion syndrome. Treatment focuses on addressing the individual’s symptoms and supporting developmental progress. Common interventions include:

• Speech, occupational, and physical therapy: For motor and language delays

• Early intervention and special education services

• Behavioral therapy and psychological support: Especially for autism traits, ADHD, or emotional challenges

• Monitoring and managing medical conditions: Such as cardiac, renal, or orthopedic anomalies

• Multidisciplinary care: Involving pediatricians, geneticists, neurologists, and therapists

Prognosis

The prognosis for individuals with 22q11.2 distal deletion syndrome depends on the size of the deletion and the severity of symptoms. With early diagnosis and supportive care, many individuals can attend school, participate in daily activities, and achieve varying degrees of independence. Developmental outcomes improve significantly with early intervention and consistent therapeutic support. Life expectancy is typically normal unless major organ malformations are present.