Phelan-McDermid Syndrome

What is Phelan-McDermid syndrome?

Phelan-McDermid syndrome, also called 22q13 deletion syndrome, is a genetic disorder caused by deletion of part of chromosome 22 or a defect in a gene called SHANK3.

The disorder can cause a wide range of symptoms varying in severity. These symptoms could include global developmental delay/intellectual disability, motor skills deficits, delayed or absent speech, autism spectrum disorder and minor dysmorphic features.

What are the symptoms of Phelan-McDermid syndrome?

Symptoms of Phelan-McDermid syndrome vary from person to person. Not all children will have every symptom. Common symptoms may include:

Neurological and neurodevelopmental problems, including:

  • developmental and speech delays
  • autism spectrum disorder
  • intellectual disability
  • behavioral problems
  • seizures
  • trouble sleeping
  • low muscle tone

Cardiac problems, including:

  • Structural heart defects

Gastrointestinal problems, including:

  • constipation
  • gastroesophageal reflux
  • poor feeding

Kidney problems, including:

  • vesicoureteral reflux
  • hydronephrosis
  • renal cysts
  • renal hypoplasia or agenesis

Susceptibility to infections, including:

  • recurring ear infections
  • upper respiratory tract infections

What are the causes of Phelan-McDermid syndrome?

Phelan-McDermid syndrome results from deletion of a piece of DNA in chromosome 22, near the end of the chromosome’s long (“q”) arm, or a change in a single gene on chromosome 22 known as SHANK3. Researchers are trying to learn whether patients with SHANK3 changes alone versus those with the chromosome 22 deletion have any differences in symptoms. What’s known is that the SHANK3 protein is involved in the functioning of the synapses, the connections between brain cells. When SHANK3 is defective or absent, there is a defect in cell-to-cell communication within the brain. However, recent research has also found that the chromosome 22 deletion does not always involve loss of SHANK3.

How is Phelan-McDermid syndrome diagnosed?

Your child may have many tests before receiving a diagnosis of Phelan-McDermid syndrome. The starting point is a careful history and physical examination. Additional studies may include a brain magnetic resonance image (MRI).

Genetic testing is an important part of the evaluation. Your child may need to have blood drawn for a test called chromosomal microarray, which can detect whether a piece of chromosome 22 is deleted. Another test specifically looks for changes in the SHANK3 gene.

Children who have any symptoms associated with Phelan-McDermid syndrome should consider further clinical evaluation and genetic testing.

What are the treatment options for Phelan-McDermid syndrome?

There is no one treatment specifically for Phelan-McDermid syndrome. Treatment is centered on treating the symptoms and careful screening for any associated disorders. Clinical trials are underway looking for new treatments for this disorder.

How we care for Phelan-McDermid syndrome

The Boston Children’s Hospital Developmental Neurogenetics Program provides diagnosis and treatment of symptoms for children with a diagnosis of Phelan-McDermid syndrome.

Our team of specialists has a deep knowledge of Phelan-McDermid syndrome and can provide specialty care for the many symptoms related to the condition, including autism, developmental delay, attention deficit hyperactivity disorder and other behavioral challenges, insomnia, epilepsy, neuromuscular abnormalities, heart problems, gastrointestinal problems and kidney problems.

In addition, the Translational Neuroscience Center (TNC) at Boston Children’s is at the forefront of research in rare neurological and genetic conditions. Boston Children’s is part of a long-term “natural history” study that is following children with Phelan-McDermid syndrome over time to track their symptoms and compare these with their genetic information.

Families help build insights on Phelan-McDermid syndrome

A long-term observational study, a patient registry and a "big data" project are bringing new knowledge about this rare condition.

Read more

Jacob-Phelan-McDermid