22q13 deletion syndrome

Overview

22q13 deletion syndrome, also known as Phelan–McDermid syndrome, is a rare genetic disorder caused by the deletion of genetic material at the terminal end of the long arm of chromosome 22, specifically at region q13. It is associated with developmental delay, intellectual disability, severe speech impairment, low muscle tone (hypotonia), and autistic behaviors. The condition is highly variable in severity and may include a wide range of neurological, physical, and behavioral features. It was first described in the late 1990s and continues to be better understood with advances in genetic testing.

Causes

22q13 deletion syndrome is caused by a deletion of the SHANK3 gene and other genes in the 22q13 region. The SHANK3 gene plays a crucial role in the development and function of synapses in the brain, which are essential for learning and communication.

The deletion typically occurs as a de novo (spontaneous) event, meaning it is not inherited from the parents. However, in some cases, it can be inherited from a parent with a balanced chromosomal rearrangement (such as a translocation). The size of the deletion can vary, and larger deletions usually result in more complex symptoms due to the loss of additional genes beyond SHANK3.

Symptoms

Symptoms of 22q13 deletion syndrome vary widely depending on the size of the deletion and the specific genes involved. Common features include:

• Global developmental delay: Especially in motor and language skills

• Severe speech and language impairment: Many individuals are nonverbal or have limited vocabulary

• Intellectual disability: Typically mild to moderate

• Autism spectrum disorder (ASD) traits: Including limited social interaction, repetitive behaviors, and sensory sensitivities

• Hypotonia (low muscle tone): Often present from birth

• Feeding difficulties: Especially in infancy

• Sleep disturbances

• Increased pain tolerance

• Minor dysmorphic features: Such as full or puffy cheeks, long eyelashes, or large hands

• Seizures: In a subset of individuals

Diagnosis

Diagnosis is based on genetic testing and clinical features. The following diagnostic tools are used:

• Chromosomal microarray analysis (CMA): The most sensitive method for detecting deletions in the 22q13 region

• FISH (Fluorescence in situ hybridization): May be used to confirm a suspected deletion

• SHANK3 gene sequencing: To identify point mutations or very small deletions affecting SHANK3 only

• Parental testing: Determines if the deletion was inherited or de novo

Diagnosis is often considered in children with severe speech delay, autism-like behaviors, and hypotonia.

Treatment

There is no cure for 22q13 deletion syndrome. Treatment is supportive and focuses on improving quality of life and promoting development. A multidisciplinary team approach is typically used, and may include:

• Speech and language therapy: With augmentative and alternative communication (AAC) tools for nonverbal individuals

• Occupational and physical therapy: To address motor delays and hypotonia

• Behavioral therapy: Especially for managing autism spectrum symptoms

• Educational support: Special education programs with individualized learning plans (IEPs)

• Medical management: For seizures, feeding issues, or sleep problems

• Genetic counseling: For families seeking information about recurrence risk

Prognosis

The prognosis for individuals with 22q13 deletion syndrome depends on the size of the deletion and the specific symptoms. While most individuals will have lifelong intellectual and communication challenges, many make progress with early and consistent therapy. Life expectancy is generally not significantly affected unless there are serious medical complications. With appropriate support, many individuals can develop functional communication, basic motor independence, and social skills suited to their abilities.