New research led by scientists at the Seaver Autism Center for Research and Treatment at Mount Sinai has unveiled a striking finding: Phelan-McDermid syndrome (PMS), a rare genetic disorder, is likely much more prevalent in the general population than previous medical estimates had suggested. The findings, published in the journal Autism Research, provide a revised prevalence estimate of roughly 1 in 7,300 people, a figure that carries significant implications for clinical practice, patient advocacy, and the development of targeted therapies.
Phelan-McDermid syndrome is a complex genetic condition primarily caused by a deletion or mutation involving the SHANK3 gene located on chromosome 22. This specific gene is crucial for the development and function of synapses, the junctions where nerve cells communicate. When SHANK3 is disrupted, the resulting neurodevelopmental impact can be profound, leading to a broad spectrum of medical, intellectual, and behavioral challenges. Many individuals diagnosed with the syndrome also meet the clinical criteria for autism spectrum disorder (ASD). In fact, experts believe that genetic variations affecting the SHANK3 gene account for as many as one percent of all cases of autism spectrum disorder, highlighting its importance in the broader landscape of neurodevelopmental research.
Genetic Data Reveal a Much Larger Population
To arrive at a more accurate estimate of the condition’s prevalence, the research team at Mount Sinai embarked on a massive data-gathering mission. They collaborated with a wide array of stakeholders, including prominent genetic testing laboratories, academic medical centers, and established autism research programs. By pooling and analyzing data from nearly 180,000 individuals who had undergone genetic testing as part of their autism assessment, the team was able to conduct an analysis of unprecedented scope.
The study integrated information from ten separate, high-level sources. These included industry leaders and research initiatives such as GeneDx, Labcorp, Ambry Genetics, the SPARK research study, and the Autism Sequencing Consortium, alongside clinical data provided by several major children’s hospitals. By synthesizing this diverse dataset, the researchers sought to overcome the limitations of smaller, localized studies that have historically underestimated the true footprint of rare genetic disorders.
After meticulously accounting for several variables—including the reality of undiagnosed cases, inherent limitations in current genetic testing technology, and the subset of individuals with Phelan-McDermid syndrome who do not necessarily meet the diagnostic criteria for autism—the researchers calculated a prevalence of 13.7 cases per 100,000 people. This translates to approximately 1 in 7,300 individuals. This estimate represents a significant departure from earlier, more conservative figures. If these findings hold true on a national scale, it suggests that more than 45,000 people in the United States could be living with Phelan-McDermid syndrome, a number far higher than previously anticipated by many clinicians.
Tess Levy, MSc, an Assistant Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai and a certified genetic counselor at the Seaver Autism Center, served as the first author of the paper. She points to a systemic failure in the current diagnostic landscape as the primary reason for the discrepancy between known and estimated cases. "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, leaving many children and adults without a definitive answer regarding the root cause of their symptoms."
Why Genetic Testing Could Matter
The implications of this study extend far beyond a mere statistical update. The researchers argue that broader, more equitable access to comprehensive genetic testing is not just a diagnostic convenience but a medical necessity. Identifying individuals who currently lack a diagnosis is the first step toward improving their quality of life and providing them with appropriate, specialized care.
"We recommend that every child with autism undergo genetic testing, because knowledge is power," said Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, co-founder of the Autism Sequencing Consortium, and senior author of the paper. Dr. Buxbaum believes that these findings are a catalyst for the next generation of medical breakthroughs. "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."
The study, which received support from CureSHANK and Neuren Pharmaceuticals, stands as one of the most comprehensive attempts to date to quantify the population of people affected by Phelan-McDermid syndrome. For pharmaceutical companies and researchers, the data provides a clearer roadmap for patient identification and clinical trial recruitment.
Rachel Groth, PhD, Head of External Innovation and Patient Advocacy at Neuren Pharmaceuticals, emphasized the ethical dimension of the research. "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," Groth stated.
New Treatments Are Moving Into Clinical Trials
The publication of these findings coincides with a pivotal era in Phelan-McDermid syndrome research. The landscape is shifting rapidly, with several clinical trials currently underway that utilize precision medicine approaches. These therapies are designed to address the specific biological pathways underlying the disorder, moving away from a "one-size-fits-all" approach to symptom management and toward addressing the genetic root of the condition.
For the families of those affected, receiving a formal genetic diagnosis is a transformative moment. It provides a definitive explanation for a child’s developmental challenges, but more importantly, it unlocks a gateway to specialized medical care, participation in groundbreaking research studies, and access to emerging clinical trials. Furthermore, a diagnosis allows families to connect with support networks, providing community and resources that are often difficult to find in the absence of a confirmed medical cause.
Geraldine Bliss, Board Chair of CureSHANK, expressed strong support for the study’s findings and the urgency they imply. "This study confirms what many families, clinicians, and advocates have suspected for years," Bliss said. "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 of the study also reinforce the advocacy work being done by organizations like CureSHANK, which is actively pushing for expanded insurance coverage and broader accessibility to genetic screening. These efforts are aligned with the goals of "Start Genetic," a global awareness campaign designed to encourage patients, families, and healthcare providers to prioritize genetic testing in the diagnostic journey.
The broader message from the research team at Mount Sinai is clear: while science has made massive strides in understanding the genetic architecture of autism and related syndromes, these advances in precision medicine can only reach the patients who need them most if they are first identified. By closing the gap in diagnosis, the medical community can move closer to a future where every individual with Phelan-McDermid syndrome has the opportunity to benefit from the rapidly evolving landscape of targeted, life-changing therapies.
