"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," said Tess Levy, MSc, Assistant Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai and a certified genetic counselor at the Seaver Autism Center. Levy, who served as the first author of the paper, noted that the barriers to diagnosis are often systemic rather than medical. "Families may also face insurance barriers or may receive tests that do not adequately evaluate the SHANK3 gene. Without specific, high-resolution testing, the underlying cause of a child’s developmental challenges can remain a mystery indefinitely."
Why Genetic Testing Could Matter
The researchers emphasize that the implications of this study extend far beyond statistical curiosity. They argue that broader, more equitable access to genetic testing is a clinical necessity that could help identify thousands of people who currently have no specific diagnosis for their symptoms. For many families, receiving a diagnosis of Phelan-McDermid syndrome is the end of a long and exhausting "diagnostic odyssey" characterized by years of uncertainty and ineffective treatments.
The Seaver Autism Center team advocates for a proactive approach to neurodevelopmental care. They suggest that genetic testing should not be viewed as a luxury or a secondary option, but as a primary diagnostic tool for any individual presenting with symptoms on the autism spectrum or with significant developmental delays.
"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’s perspective is rooted in the emerging field of precision medicine, which seeks to tailor medical treatments to the specific genetic profile of the patient.
"These genetic findings allow researchers to design more targeted clinical trials for potential therapies," Dr. Buxbaum explained. "I truly believe that within the next five years, we’ll see successful examples of new treatments coming from these genetic discoveries. But those treatments can only be effective if we know which patients have the specific genetic markers that the drugs are designed to target."
The study, which received vital support from the advocacy organization CureSHANK and Neuren Pharmaceuticals, is being described as one of the most comprehensive and rigorous attempts yet to quantify the population of people living with Phelan-McDermid syndrome. The partnership between academic researchers, pharmaceutical innovators, and patient advocates underscores the shared urgency in finding and helping this "hidden" population.
