22q11.2 duplication syndrome

Overview

22q11.2 duplication syndrome is a rare genetic condition caused by an extra copy (duplication) of a small segment of chromosome 22 at position q11.2. This syndrome is part of a group of disorders known as copy number variations (CNVs) and is considered the counterpart of the more well-known 22q11.2 deletion syndrome (DiGeorge syndrome). The clinical presentation is highly variable—ranging from individuals with no noticeable symptoms to those with significant developmental and medical issues. Common features include developmental delays, learning disabilities, speech problems, and behavioral challenges.

Causes

The syndrome is caused by a duplication of a segment of chromosome 22 in the q11.2 region. The duplicated segment usually ranges from 1.5 to 3 million base pairs and includes multiple genes essential for normal development.

The duplication can occur:

• De novo (sporadically): Arising for the first time in the affected individual, with no family history

• Inherited: From a parent who may have mild or no symptoms due to incomplete penetrance or variable expressivity

Symptoms

The symptoms of 22q11.2 duplication syndrome are highly variable and can range from completely asymptomatic to moderate developmental and medical issues. Common features include:

• Developmental delays: Especially in speech and motor skills

• Learning disabilities: Mild to moderate intellectual disability is possible

• Hypotonia (low muscle tone)

• Delayed speech or expressive language disorder

• Autism spectrum disorder (ASD): Or traits such as social difficulties and repetitive behaviors

• Attention deficit hyperactivity disorder (ADHD)

• Behavioral challenges: Including anxiety, impulsivity, and mood disorders

• Congenital anomalies: Such as heart defects, cleft palate, or urogenital abnormalities (less frequent than in deletion cases)

• Facial features: May include a broad nasal bridge, long face, or minor ear anomalies

Many individuals with the duplication lead typical lives, especially when early developmental support is provided.

Diagnosis

Diagnosis is typically made using genetic testing. Steps include:

• Chromosomal microarray analysis (CMA): The preferred method to detect the 22q11.2 duplication

• FISH (Fluorescence in situ hybridization): May be used to confirm duplications if CMA is unavailable

• Parental testing: Helps determine whether the duplication was inherited or de novo

Genetic testing is often performed when developmental delays, behavioral concerns, or congenital anomalies prompt further investigation.

Treatment

There is no cure for 22q11.2 duplication syndrome. Treatment is symptom-based and tailored to the individual's specific needs. A multidisciplinary team approach is often beneficial. Management may include:

• Speech, occupational, and physical therapy: To address language, coordination, and motor delays

• Special education services: With individualized education plans (IEPs)

• Behavioral therapy: For autism traits, attention difficulties, or emotional regulation

• Medical care: For congenital heart or urogenital defects if present

• Psychological support: For anxiety, ADHD, or mood-related concerns

• Genetic counseling: For families planning future pregnancies or understanding inheritance

Prognosis

The prognosis for individuals with 22q11.2 duplication syndrome is generally good, particularly with early diagnosis and developmental support. Many children reach developmental milestones with delay, and some catch up over time. While some individuals may require special education or therapy long-term, others may function independently with little intervention. Life expectancy is typically normal unless major congenital anomalies are present.