New research led by scientists at the Seaver Autism Center for Research and Treatment at Mount Sinai suggests that Phelan-McDermid syndrome (PMS) may be much more common than earlier estimates indicated. The findings, published in the scientific journal Autism Research, estimate that the rare genetic condition affects roughly 1 in every 7,300 people. This updated prevalence figure represents a substantial shift in the medical community’s understanding of the disorder and indicates that tens of thousands of individuals may currently be living with the condition without a proper diagnosis.
Phelan-McDermid syndrome is a rare genetic disorder that is typically caused by a deletion or a mutation involving the SHANK3 gene located on chromosome 22. This specific genetic disruption can lead to a broad and complex range of medical, intellectual, and behavioral challenges for affected individuals. Clinical observations have established that most people who are diagnosed with the syndrome also meet the diagnostic criteria for autism spectrum disorder. Furthermore, genetic changes and mutations affecting the SHANK3 gene are widely believed by researchers to account for as many as one percent of all diagnosed autism spectrum disorder cases globally.
To arrive at their updated estimates regarding how common the condition may actually be, researchers at Mount Sinai collaborated closely with a wide network of genetic testing laboratories, prominent academic medical centers, and specialized autism research programs. As part of this comprehensive investigation, the research team carefully examined extensive genetic data drawn from nearly 180,000 individuals diagnosed with autism who had previously undergone genetic testing.
The scope of the analysis was unusually broad, combining information gathered from ten separate, high-volume sources. These contributing entities included major commercial and specialized testing organizations such as GeneDx, Labcorp, and Ambry Genetics, alongside large-scale research initiatives like the SPARK research study and the Autism Sequencing Consortium, as well as several major children’s hospitals across the healthcare landscape.
By rigorously analyzing this vast pool of data, the researchers sought to account for various confounding factors that often mask the true prevalence of rare genetic conditions. Their calculations carefully factored in undiagnosed cases, the inherent limitations and variations in historical genetic testing practices, and individuals who are living with Phelan-McDermid syndrome but do not happen to meet the clinical criteria for autism.
Following these adjustments, the research team estimated a national and broader prevalence of 13.7 cases per 100,000 people. When calculated out, that works out to approximately 1 in every 7,300 individuals. This newly calculated estimate represents a major and notable departure from previous prevalence figures, suggesting that more than 45,000 people in the United States alone could potentially be living with Phelan-McDermid syndrome.
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 published paper, shed light on why such a vast discrepancy exists between historical records and the new findings.
"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," Levy explained. "Families may also face insurance barriers or may receive tests that do not adequately evaluate the SHANK3 gene."
Why Genetic Testing Could Matter
The implications of the new study extend far beyond mere statistical updates, as the researchers emphasize that broader and more equitable access to comprehensive genetic testing could profoundly help identify individuals who currently navigate life without a diagnosis. Identifying these patients is not merely an academic exercise; it carries direct, tangible benefits for clinical management and future therapeutic interventions.
Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, co-founder of the Autism Sequencing Consortium, and senior author of the paper, emphasized the critical importance of expanding screening protocols for young patients.
"We recommend that every child with autism undergo genetic testing, because knowledge is power," said Dr. Buxbaum. "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."
This landmark study was supported by CureSHANK and Neuren Pharmaceuticals, and it is widely described by participating institutions as one of the most comprehensive and rigorous attempts yet to accurately estimate how many people may be affected by Phelan-McDermid syndrome. Industry partners underscored the ethical and practical urgency of bridging the gap between unknown and diagnosed cases.
"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," said Rachel Groth, PhD, Head of External Innovation and Patient Advocacy at Neuren Pharmaceuticals. "Patients cannot benefit from these advances if they never receive a diagnosis."
New Treatments Are Moving Into Clinical Trials
The publication of these findings arrives at a uniquely critical juncture for Phelan-McDermid syndrome research and therapeutic development. Several clinical trials are currently underway, marking a shift toward precision medicine approaches that are specifically aimed at addressing the underlying biological mechanisms of the disorder rather than merely managing outward symptoms.
For individuals living with the condition and their families, receiving an accurate genetic diagnosis can now mean much more than simply learning the root biological cause of their developmental and medical challenges. A formal diagnosis may also provide vital access to specialized medical care, specialized research studies, upcoming clinical trials, supportive patient networks, and potentially transformative disease-modifying treatments that are currently moving through the clinical pipeline.
Advocacy groups and community leaders have strongly echoed these sentiments, highlighting the emotional and practical relief that comes with proper identification. Geraldine Bliss, Board Chair of CureSHANK, reflected on the profound impact of the research for affected families and clinicians alike.
"This study confirms what many families, clinicians, and advocates have suspected for years," said 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 important."
The results of the study also reinforce ongoing organizational initiatives led by CureSHANK to aggressively expand access to comprehensive genetic testing. These efforts directly support the core goals of Start Genetic, a global awareness campaign designed to encourage patients, families, healthcare providers, and advocacy groups to prioritize genetic evaluation from the earliest possible stage of clinical care.
Ultimately, the broader message emerging from the Mount Sinai study is that the extraordinary scientific advances being made in the field of precision medicine can only successfully reach patients who have first been accurately identified and diagnosed. As clinical trials progress and new therapeutic avenues emerge, researchers and advocates alike hope that expanded screening will bring thousands of previously overlooked individuals into the fold of modern medical care.
