New research led by scientists at the Seaver Autism Center for Research and Treatment at Mount Sinai suggests that Phelan-McDermid syndrome 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 7,300 people, a revelation that could significantly alter how medical professionals approach diagnosis and therapeutic development for thousands of families.
Phelan-McDermid syndrome is a rare genetic disorder caused by a deletion or mutation involving the SHANK3 gene located on chromosome 22. This crucial gene plays a fundamental role in the development and function of synapses, the connections between nerve cells in the brain. Disruptions to this gene can lead to a broad and complex range of medical, intellectual, and behavioral challenges for affected individuals. Most people diagnosed with the syndrome also meet the diagnostic criteria for autism spectrum disorder, and alterations affecting the SHANK3 gene are believed to account for as much as one percent of all autism spectrum disorder cases globally.
To arrive at their new prevalence estimates, Mount Sinai researchers collaborated closely with prominent genetic testing laboratories, academic medical centers, and specialized autism research programs. The multidisciplinary team undertook a massive data-mining effort, examining genetic records from nearly 180,000 individuals with autism who had previously undergone comprehensive genetic testing.
This rigorous analysis successfully combined information from ten separate and diverse sources to ensure a broad and representative sample. Participating institutions and resources included GeneDx, Labcorp, Ambry Genetics, the landmark SPARK research study, the Autism Sequencing Consortium, and several major children’s hospitals across the country.
By carefully evaluating this vast pool of genetic data, the research team was able to account for historical blind spots, including undiagnosed cases, limitations inherent in older or narrower genetic testing panels, and individuals living with Phelan-McDermid syndrome who do not happen to meet the clinical criteria for autism spectrum disorder. Through these adjustments, the researchers calculated an estimated prevalence of 13.7 cases per 100,000 people, which translates directly to approximately 1 in every 7,300 individuals.
This new estimate represents a dramatic and major shift from previous epidemiological figures. The findings suggest that more than 45,000 people in the United States alone could be living with Phelan-McDermid syndrome, a figure vastly higher than historical counts that relied solely on localized registries or smaller clinical cohorts.
Tess Levy, MSc, an Assistant Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai, a certified genetic counselor at the Seaver Autism Center, and the first author of the published paper, explained the reasoning behind the substantial gap between known and estimated cases. She noted that this discrepancy is likely due in large part to the fact that many individuals with developmental disabilities and autism are never offered genetic testing in clinical practice. Furthermore, families frequently face significant insurance barriers or may receive diagnostic tests that fail to adequately evaluate the SHANK3 gene, leaving many cases hidden in plain sight.
The researchers emphasize that broader, more equitable access to comprehensive genetic testing could help identify thousands of people who currently navigate life without a clear diagnosis.
Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, co-founder of the Autism Sequencing Consortium, and senior author of the paper, underscored the clinical importance of expanding diagnostic outreach. He recommended that every child diagnosed with autism undergo comprehensive genetic testing, stating that knowledge is power. According to Dr. Buxbaum, these critical genetic findings allow researchers to design much more targeted clinical trials for potential therapies. He expressed strong optimism that within the next five years, the medical community will witness successful examples of groundbreaking new treatments emerging directly from these foundational genetic discoveries.
The study, which received critical support from CureSHANK and Neuren Pharmaceuticals, is widely described by experts as one of the most comprehensive and methodologically rigorous attempts yet to estimate the true population burden of Phelan-McDermid syndrome.
Rachel Groth, PhD, Head of External Innovation and Patient Advocacy at Neuren Pharmaceuticals, highlighted the ethical imperative driving the research. She explained that Neuren Pharmaceuticals initiated this landmark prevalence study in collaboration with the Seaver Autism Center at Mount Sinai and CureSHANK because, with new treatments actively moving closer to clinical reality, identifying these individuals has become an urgent priority. Dr. Groth stressed that vulnerable patients cannot possibly benefit from cutting-edge medical advances if they never receive an accurate diagnosis in the first place.
These new findings arrive at a critically important juncture for Phelan-McDermid syndrome research. Several clinical trials are currently underway, including advanced precision medicine approaches specifically designed to target the unique underlying biology of the disorder.
For people living with the condition and their families, receiving a timely and accurate genetic diagnosis can now mean far more than simply understanding the root cause of their symptoms. It can also provide crucial access to specialized medical care, dedicated research studies, upcoming clinical trials, supportive patient networks, and potentially transformative disease-modifying treatments that are currently moving through the development pipeline.
Geraldine Bliss, Board Chair of CureSHANK, reflected on the emotional and practical weight of the new data for the advocacy community. She stated that the study formally confirms what many families, clinicians, and patient advocates have strongly suspected for years. There are likely tens of thousands of individuals walking around with Phelan-McDermid syndrome who have never received a genetic diagnosis. At a historical moment when multiple therapeutics are advancing rapidly into clinical trials, Ms. Bliss noted that finding these individuals has truly never been more important.
The results also heavily reinforce CureSHANK’s ongoing national and international push to dramatically expand access to genetic testing. Furthermore, the findings support the broader goals of Start Genetic, a global awareness campaign designed to encourage patients, families, health care providers, and advocacy groups to think genetic first when evaluating developmental and neurological conditions.
The overarching message conveyed by the research team and supporting organizations is clear: modern advances in precision medicine and targeted therapeutics can only reach the patients who have first been accurately identified and diagnosed. As clinical trials progress and awareness campaigns gain momentum, the medical community hopes that this newly revealed population of individuals will finally find the answers, care, and treatments they need.