Phelan-McDermid syndrome prevalence may be far higher than once believed, according to new research led by the Seaver Autism Center for Research and Treatment at Mount Sinai. The study, published in Autism Research, estimates the condition affects about 1 in 7,300 people.
Phelan-McDermid syndrome is a genetic disorder tied to deletions or mutations involving the SHANK3 gene on chromosome 22. It is associated with medical, intellectual, and behavioral challenges. Most individuals with the syndrome meet diagnostic criteria for autism spectrum disorder, and alterations in SHANK3 are thought to account for up to 1 percent of autism cases.
Phelan-McDermid syndrome prevalence estimate
To assess how common the condition may be, Mount Sinai investigators partnered with genetic testing laboratories, academic centers, and autism research programs. The team analyzed data from nearly 180,000 people with autism who had undergone genetic testing, drawing on 10 sources that included GeneDx, Labcorp, Ambry Genetics, the SPARK research study, the Autism Sequencing Consortium, and several major children’s hospitals.
Accounting for undiagnosed cases, testing limitations, and people with the syndrome who do not meet criteria for autism, the researchers estimated a prevalence of 13.7 per 100,000 people. That equates to roughly 1 in 7,300 individuals.
The revised figure marks a substantial shift from earlier estimates and indicates 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 individuals with developmental disabilities and autism are never offered genetic testing. Families may also face insurance barriers or may receive tests that do not adequately evaluate the SHANK3 gene,” said Tess Levy, MSc, Assistant Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai and a certified genetic counselor at the Seaver Autism Center.
Why genetic testing access matters
The researchers said wider access to genetic testing could help identify people who currently lack a diagnosis.
“We recommend that every child 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 within the next five years, we’ll see successful examples of new treatments coming from these genetic discoveries,” said Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center and senior author of the paper.
Backed by CureSHANK and Neuren Pharmaceuticals, the analysis is described as one of the most comprehensive efforts to date to estimate how many people may have the condition.
“Neuren Pharmaceuticals initiated this landmark PMS prevalence study in collaboration with the Seaver Autism Center at Mount Sinai and CureSHANK because, with new treatments moving 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, Head of External Innovation and Patient Advocacy at Neuren Pharmaceuticals.
New treatments entering clinical trials
The findings arrive as multiple clinical trials advance, including precision medicine approaches that target the biology underlying the disorder. For affected individuals and families, a genetic diagnosis can open doors to specialized medical care, research participation, clinical trials, patient communities, and the prospect of disease-modifying therapies.
“This study confirms what many families, clinicians, and advocates have suspected for years,” said CureSHANK Board Chair, Geraldine Bliss. “There are likely tens of thousands of individuals with Phelan-McDermid syndrome who have never received a genetic diagnosis. At a time when multiple therapeutics are advancing into clinical trials, finding these individuals has never been more important.”
The results bolster CureSHANK’s efforts to expand access to genetic testing and align with the Start Genetic campaign, a global initiative urging patients, families, clinicians, and advocacy groups to consider genetic evaluation early.
The broader takeaway, according to the researchers and advocates, is that progress in precision medicine will only reach patients who are identified and diagnosed. Related work is also exploring how mice given brain organoids to study human neural development may inform future treatments for neurological and developmental conditions.