Phelan-McDermid syndrome may be considerably more common than previously thought, according to research from the Seaver Autism Center for Research and Treatment at Mount Sinai.
The study, published in Autism Research, estimates that this genetic condition affects about one in 7,300 people. Earlier estimates had put the condition much lower.
This genetic disorder involves the SHANK3 gene on chromosome 22.
A deletion or mutation affecting this gene can cause intellectual, behavioral and medical problems that vary widely from person to person.
Autism is also very common among people with Phelan-McDermid syndrome.
Researchers estimate that SHANK3-related changes may account for up to 1% of autism spectrum disorder cases.
How Common Is Phelan-McDermid Syndrome?
Mount Sinai researchers looked at genetic data from nearly 180,000 people with autism.
They worked with genetic testing companies, medical centers and autism research programs to bring together information from 10 different sources.
After taking undiagnosed cases, limitations of genetic testing and people with Phelan-McDermid syndrome who do not have autism into account, the researchers calculated a prevalence of 13.7 cases per 100,000 people.
Using that estimate, more than 45,000 people in the U.S. could have Phelan-McDermid syndrome.
I was once a provider for an agency that services developmentally disabled adults.
One of the individuals had this genetic disorder. He was autistic and also had an intellectual disability.
This handsome young man had no so-called behaviors and was very easy to work with, very compliant.
Though he was pretty good at using his phone for searches of his special interests, and was able to fluently read out loud pamphlets and a simple book that I had put before him (his comprehension, though, was very questionable), he had limited spoken language in terms of spontaneous speech, and was not able to speak narratives.
There was the occasional phrase or simple question, and he also exhibited echolalia: repeating the last word or two of a question asked of him.
Why Many Cases May Be Missed
The researchers say a major reason for the difference between diagnosed and estimated cases is limited access to genetic testing.
Many people with autism or an intellectual deficit are never offered genetic testing.
Insurance problems can also get in the way. In other cases, testing may not adequately examine the SHANK3 gene.
Tess Levy, MSc, a Mount Sinai psychiatry professor and genetic counselor at the Seaver Autism Center, says in the report that these factors likely explain much of the gap between known cases and the larger estimated population.
Genetic Testing and Autism
A genetic diagnosis can identify the underlying cause in some cases and can also help researchers develop more targeted clinical trials, leading to new treatments.
A genetic diagnosis may help connect patients with specialized medical care, research studies, clinical trials, support groups and potential disease-modifying treatments.
Why the New Estimate Is Significant
The researchers say the difference between documented cases and the number suggested by genetic data points to a large group of people who may have the syndrome without knowing it.
People with this condition don’t necessarily look different physically, especially without close scrutiny.
The individual I had worked with was tall and had no distinguishing physical characteristics.
However, he had been diagnosed at some point in his life with Phelan-McDermid syndrome — testing that was likely prompted by a medical situation that came with the disorder.
The study says that several clinical trials are already underway, as of 2026, for Phelan-McDermid syndrome.
