A new analysis published in Autism Research estimates Phelan-McDermid syndrome prevalence at roughly 1 in 7,300 people, a figure that implies more than 45,000 Americans could be living with the condition. The researchers, based at the Seaver Autism Center for Research and Treatment at Mount Sinai, say the gap between estimated and confirmed cases is largely explained by a persistent failure to offer genetic testing to people with developmental disabilities and autism.
Phelan-McDermid syndrome (PMS) is a genetic disorder caused by a deletion or mutation involving the SHANK3 gene on chromosome 22. It can produce a broad range of medical, intellectual, and behavioural challenges. Most people who have it also meet the criteria for autism spectrum disorder, and changes affecting SHANK3 are believed to account for as many as one per cent of autism spectrum disorder cases.
What the Phelan-McDermid Syndrome Prevalence Study Found
To arrive at their estimate, the Mount Sinai team examined data from nearly 180,000 people with autism who had undergone genetic testing. The analysis drew on ten separate sources: among them Neuren Pharmaceuticals-affiliated data, GeneDx, Labcorp, Ambry Genetics, the SPARK research study, the Autism Sequencing Consortium, and several major children’s hospitals.
After accounting for undiagnosed cases, limits in genetic testing, and people with PMS who do not meet the criteria for autism, the researchers arrived at a prevalence of 13.7 cases per 100,000 people, or approximately 1 in 7,300. That represents a substantial upward revision from previous estimates.
Tess Levy, MSc, Assistant Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai, a certified genetic counsellor at the Seaver Autism Center, and first author of the paper, pointed to structural barriers as the main driver of the shortfall. ‘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,’ she said.
Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, co-founder of the Autism Sequencing Consortium, and senior author of the paper, made the clinical case for expanding testing. ‘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,’ he said.
Clinical Trials Are Already Under Way
The urgency the researchers attach to diagnosis is not purely academic: several trials targeting the underlying biology of PMS are now active. According to CheckRare, the first patient was dosed in February 2026 in a Phase 3 trial of NNZ-2591, an IGF-1 analogue developed by Neuren Pharmaceuticals in collaboration with the Seaver Autism Center and CureSHANK. Known as the Koala trial, it is evaluating the safety and efficacy of NNZ-2591 in children aged 3 to 12 years with PMS, and includes a 52-week open-label extension study, according to EurekAlert!.
A separate gene therapy approach is also showing early movement. CheckRare reports that Jaguar Gene Therapy’s SHANK3 minigene replacement therapy has been dosed in five patients, with no serious adverse events related to the therapy and early signs of improvement observed. Both developments remain at an early stage, and neither constitutes an approved treatment.
Rachel Groth, PhD, Head of External Innovation and Patient Advocacy at Neuren Pharmaceuticals, framed the prevalence study in explicitly ethical terms. ‘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,’ she said.
The study was supported by CureSHANK and Neuren Pharmaceuticals, and the researchers describe it as one of the most comprehensive attempts yet to estimate how many people may have Phelan-McDermid syndrome. CureSHANK Board Chair Geraldine Bliss said the results ‘confirm what many families, clinicians, and advocates have suspected for years,’ adding that ‘finding these individuals has never been more important’ given the number of therapeutics now advancing into trials.
The findings also support Start Genetic, a global awareness campaign encouraging patients, families, healthcare providers, and advocacy groups to prioritise genetic testing. The Phelan-McDermid syndrome prevalence estimate puts a specific number on what that campaign is working against: a population of tens of thousands who may have a diagnosable, and now potentially treatable, condition and no name yet for it.
