New research led by scientists at the Seaver Center for Autism Research and Treatment at Mount Sinai suggests that Phelan-McDermid syndrome (PMS) may be much more common than previous estimates indicated. The findings, published in autism researchThey estimate that the condition affects approximately 1 in 7,300 people.
Phelan-McDermid syndrome is a rare genetic disorder caused by a deletion or mutation involving the SHANK3 gene on chromosome 22. It can cause a wide range of medical, intellectual, and behavioral challenges. Most people with the syndrome also meet criteria for autism spectrum disorder, and changes affecting SHANK3 are thought to account for up to one percent of autism spectrum disorder cases.
Genetic data reveals much larger population
To estimate how common the condition may be, Mount Sinai researchers worked with genetic testing laboratories, academic medical centers and autism research programs. The team examined data from nearly 180,000 people with autism who had undergone genetic testing.
Their analysis combined information from ten different sources, including GeneDx, Labcorp, Ambry Genetics, the SPARK research study, the Autism Sequencing Consortium, and several major children’s hospitals.
After accounting for undiagnosed cases, limitations in genetic testing, and people with Phelan-McDermid syndrome who do not meet autism criteria, the researchers estimated a prevalence of 13.7 cases per 100,000 people. That equates to approximately 1 in every 7,300 people.
The estimate represents a major change from previous figures and suggests that more than 45,000 people in the United States may be living with Phelan-McDermid syndrome.
“The large gap between known and estimated cases is likely due in large part to the fact that many people with developmental disabilities and autism are never offered genetic testing. Families may also face insurance barriers or receive tests that do not adequately assess the SHANK3 gene,” said Tess Levy, MSc, assistant professor of psychiatry at the Icahn School of Medicine at Mount Sinai, a certified genetic counselor at the Seaver Autism Center, and first author of the paper.
Why genetic testing might be important
Researchers say broader access to genetic testing could help identify people who currently have no diagnosis.
“We recommend that all children with autism undergo genetic testing, because knowledge is power. These genetic findings allow researchers to design more targeted clinical trials for potential therapies. I truly believe that in the next five years we will see successful examples of new treatments coming from these genetic discoveries,” said Joseph D. Buxbaum, PhD, director of the Seaver Autism Center, co-founder of the Autism Sequencing Consortium, and lead author of the paper.
Backed by CureSHANK and Neuren Pharmaceuticals, the study is described as one of the most comprehensive attempts yet to estimate how many people may have Phelan-McDermid syndrome.
“Neuren Pharmaceuticals initiated this landmark PMS prevalence study in collaboration with the Seaver Autism Center at Mount Sinai and CureSHANK because, as new treatments become closer to reality, identifying these individuals has become an ethical imperative. Patients cannot benefit from these advances if they never receive a diagnosis,” said Rachel Groth, PhD, director of external innovation and patient advocacy at Neuren Pharmaceuticals.
New treatments are moving into clinical trials
The findings come at an important time for Phelan-McDermid syndrome research. Several clinical trials are currently underway, including precision medicine approaches targeting the underlying biology of the disorder.
For people with this condition and their families, receiving a genetic diagnosis now can mean more than simply knowing the cause of their symptoms. It can also provide access to specialized medical care, research studies, clinical trials, patient support networks, and potentially disease-modifying treatments.
“This study confirms what many families, doctors and advocates have suspected for years,” said CureSHANK Board President Geraldine Bliss. “There are likely tens of thousands of people with Phelan-McDermid syndrome who have never received a genetic diagnosis. At a time when multiple therapies are moving toward clinical trials, finding these people has never been more important.”
The results also reinforce CureSHANK’s push to expand access to genetic testing and support the goals of Start Genetic, a global awareness campaign that encourages patients, families, healthcare providers and advocacy groups to think genetics first.
The broader message is that advances in precision medicine can only reach patients who have been identified and diagnosed first.