Understanding Phelan-McDermid Syndrome

Phelan-McDermid Syndrome (PMS)—also called 22q13 Deletion Syndrome (22q13DS)—is a rare genetic syndrome in which one copy of the SHANK3 gene at the end of chromosome 22 is either missing or otherwise mutated. The SHANK3 gene is key to the development of the human nervous system, and loss of SHANK3 can impair nerve cell development, function and communication.

Though symptoms can vary, PMS is typically line characterized by low address muscle tone, absent or delayed speech, intellectual disability, and minor facial or body abnormalities. PMS can lead to behavioral symptoms that are associated with autism spectrum disorder (ASD). In fact, SHANK3 deletions or mutations are estimated to occur in 1 to 2% of patients with ASD.

It is unknown exactly how many children are born with this condition. Current estimates indicate that more than 1000 individuals around the world have the disorder, but studies suggest that many, many cases may go undiagnosed.

One goal of the program at the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai in New York City is to investigate the role of the SHANK3 gene in autism and associated conditions and in PMS/22q13DS and to determine how best to treat these conditions. The Seaver Center, one of the leading comprehensive care centers treating ASD in the country, has recently expanded its research-based clinical program to address these types of issues.

What are SHANK3 Mutations?

The SHANK3 gene is located on chromosome 22 and is one of several genes belonging to the SHANK family of genes. The Shank family has three known members: SHANK1, SHANK2, and SHANK3. Shank proteins are crucial to brain cell (nerve) communication because they play a role in forming the connection between nerve cells.

“SHANK3 is of great interest to us because it has been shown to be the gene associated with neurobehavioral symptoms in individuals with PMS,” says leading neuroscientist Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, and Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at Mount Sinai School of Medicine. “The deletion or alteration of SHANK3 interferes with appropriate nerve cell function and nerve cell communication. Understanding the function of SHANK3 would help lead to the development of more targeted treatments for PMS and SHANK3 mutations and will also lead to better treatments in autism spectrum disorders.”

Mutations in SHANK3 produce the same syndrome as that seen with 22q13 Deletion Syndrome. Individuals with a mutation in SHANK3 show poor muscle tone, absent or delayed speech, intellectual disability, and minor facial or body abnormalities. In addition, they can show behavioral symptoms that fall under the category of an autism spectrum disorder (ASD). It is now estimated that about 1% of individuals with an ASD have a deletion or mutation of SHANK3.

Genetic sequencing can identify the mutation on chromosome 22. A test called array comparative genomic hybridization (aCGH) can specifically identify the deletion on the q13 portion of chromosome 22.