A landmark study led by researchers at the Seaver Autism Center for Research and Treatment at Mount Sinai has revealed that Phelan-McDermid syndrome (PMS), a rare genetic condition, is far more common than medical literature had previously indicated. The findings, recently published in the journal Autism Research, suggest that the disorder affects approximately 1 in 7,300 individuals, a figure that significantly alters the understanding of the condition’s footprint in the general population.
Phelan-McDermid syndrome is a complex genetic disorder typically caused by a deletion or a specific mutation involving the SHANK3 gene, which is located on chromosome 22. This gene is critical for the healthy development of synapses—the junctions between nerve cells that allow for communication in the brain. When this gene is compromised, the resulting disruption can lead to a broad spectrum of medical, intellectual, and behavioral challenges. Because of the critical role SHANK3 plays in neural architecture, the syndrome is closely linked to neurodevelopmental conditions; in fact, most individuals diagnosed with PMS also meet the formal clinical criteria for autism spectrum disorder (ASD). Current scientific consensus suggests that variations or changes affecting the SHANK3 gene alone account for as much as one percent of all diagnosed cases of autism spectrum disorder globally.
Genetic Data Reveal a Much Larger Population
To arrive at a more accurate estimate of the syndrome’s prevalence, the research team at Mount Sinai spearheaded a massive data-gathering initiative. They collaborated with an expansive network of genetic testing laboratories, prominent academic medical centers, and various autism research programs to synthesize a comprehensive picture of the genetic landscape. By examining anonymized data from nearly 180,000 individuals with autism who had undergone various forms of genetic screening, the researchers were able to look for patterns that had previously been overlooked.
The analysis was exceptionally robust, integrating information from ten distinct, high-profile sources. These included industry leaders and research consortiums such as GeneDx, Labcorp, Ambry Genetics, the SPARK research study, and the Autism Sequencing Consortium. Furthermore, the team incorporated data from several major children’s hospitals, ensuring that the study represented a diverse cross-section of the pediatric population.
The methodology required careful statistical adjustment to account for several confounding factors. The researchers systematically accounted for individuals who remain undiagnosed due to limited access to healthcare, the technical limitations inherent in some genetic testing platforms, and, crucially, the subset of people with Phelan-McDermid syndrome who do not manifest the classic symptoms of autism, and thus may have been missed by studies focused exclusively on ASD cohorts. After calibrating their data to include these variables, the team estimated a prevalence of 13.7 cases per 100,000 people. This translates to a ratio of 1 in 7,300 individuals.
This new estimate represents a profound shift from historical figures, which were often based on smaller, more localized studies. When applied to the total population, these findings suggest that more than 45,000 people in the United States could be living with Phelan-McDermid syndrome—a number that is substantially higher than many clinical benchmarks previously used by doctors and health systems.
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 explains that the discrepancy between the expected prevalence and the actual number of clinical diagnoses is a result of systemic gaps in the healthcare infrastructure. "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 noted. "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 this study extend well beyond statistics; they represent an urgent call for expanded access to diagnostic tools. The researchers argue that by removing barriers to genetic testing, the medical community can identify thousands of individuals who are currently navigating life without a clear diagnosis, often lacking the specialized care and support they require.
Dr. Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center and a co-founder of the Autism Sequencing Consortium, served as the senior author of the study. He emphasizes that genetic literacy is a fundamental component of modern clinical care. "We recommend that every child with autism undergo genetic testing, because knowledge is power," Dr. Buxbaum said. "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 efforts to date to map the true scale of Phelan-McDermid syndrome. For pharmaceutical partners and patient advocacy groups, the study serves as a validation of the need for better surveillance.
"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 coincides with a pivotal moment in the trajectory of Phelan-McDermid syndrome research. After years of focusing on symptom management and supportive therapy, the field is now shifting toward precision medicine. Several clinical trials are currently underway, investigating therapeutic approaches that target the specific biological mechanisms—the underlying molecular "broken links"—that define the disorder.
For families, a formal genetic diagnosis is no longer just a label; it is a gateway to a new era of care. A diagnosis can provide access to specialized medical monitoring, longitudinal research studies, and, most importantly, the prospect of disease-modifying treatments currently being tested in clinical settings.
Geraldine Bliss, Board Chair of CureSHANK, expressed the relief felt by the advocacy community upon hearing the results. "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 are expected to strengthen the resolve of organizations like CureSHANK to lobby for more widespread, accessible genetic screening. The findings support the goals of "Start Genetic," a global awareness campaign designed to encourage patients, their families, and frontline healthcare providers to prioritize genetic evaluation as a first-line diagnostic tool.
The broader message from the research team at Mount Sinai is clear: while the landscape of precision medicine is evolving rapidly, the promise of these medical breakthroughs can only be realized if the patient population is correctly identified. As the scientific community looks toward the next decade of research, the focus remains on closing the gap between the tens of thousands of undiagnosed individuals and the life-changing therapies that are now on the horizon. By ensuring that more children and adults receive accurate genetic information, the healthcare system can transition from merely observing these conditions to actively treating the biological roots of Phelan-McDermid syndrome.
