Phelan-McDermid Syndrome Prevalence Estimated at 1 in 7,300, Far Higher Than Previously Thought
核心洞察
A new multisource analysis estimates Phelan-McDermid syndrome (搜索) affects approximately 1 in 7,300 people, dramatically exceeding prior prevalence estimates.
Researchers analyzed genetic testing data from nearly 180,000 individuals with autism across ten independent sources, including GeneDx, Labcorp, and the SPARK study.
The findings suggest more than 45,000 people in the United States may be living with the condition, with a large gap between known and estimated cases.
New research led by the Seaver Autism Center for Research and Treatment at Mount Sinai has estimated that Phelan-McDermid syndrome (搜索) (PMS) affects approximately 1 in 7,300 people, a figure dramatically higher than previous estimates suggested. Published June 28 in Autism Research, the study represents one of the most comprehensive efforts ever undertaken to measure the prevalence of this rare neurodevelopmental condition.
Phelan-McDermid syndrome (搜索) is caused by deletion or mutation of the SHANK3 (搜索) gene on chromosome 22 and can produce a wide range of medical, intellectual, and behavioral challenges. The majority of patients with the syndrome also meet criteria for autism spectrum disorder (搜索), and SHANK3 deletions or mutations are thought to account for up to one percent of autism spectrum disorder cases.
A multisource modeling approach
To overcome the diagnostic gap that has historically obscured the true prevalence of PMS, Mount Sinai researchers collaborated with genetic testing laboratories, academic medical centers, and autism research programs. They analyzed data from nearly 180,000 individuals with autism who underwent genetic testing, combining information from ten independent sources, including GeneDx, Labcorp, Ambry Genetics, the SPARK research study, the Autism Sequencing Consortium, and several leading children's hospitals.
After adjusting for undiagnosed cases, testing limitations, and individuals with PMS who do not meet criteria for autism, the investigators estimated a prevalence of 13.7 cases per 100,000 people, equivalent to about 1 in 7,300 individuals. Applied to the United States population, this suggests that more than 45,000 people may be living with the condition.
"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 (搜索) gene," said Tess Levy, MSc, Assistant Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai, certified genetic counselor at the Seaver Autism Center, and first author of the paper.
Clinical implications at a pivotal moment
The publication arrives as multiple PMS clinical trials are underway, including precision medicine approaches designed to address the underlying biology of the disorder. For individuals and families affected by this condition, a genetic diagnosis is increasingly a gateway to specialized care, research opportunities, clinical trials, patient support communities, and potentially disease-modifying therapies.
"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," said Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, co-founder of the Autism Sequencing Consortium, and senior author of the paper.
The cost of missed diagnoses
The study, supported by CureSHANK (搜索) and Neuren Pharmaceuticals, underscores the urgency behind efforts to expand access to genetic testing. CureSHANK Board Chair Geraldine Bliss emphasized the human stakes: "This study confirms what many families, clinicians, and advocates have suspected for years. There are likely tens of thousands of individuals with Phelan-McDermid syndrome (搜索) 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 findings also support the broader goals of Start Genetic, a global awareness campaign launched to encourage patients, families, health care providers, and advocacy organizations to think genetic first. The central challenge is clear: patients cannot benefit from precision medicine if they are never diagnosed.
"Every undiagnosed individual represents more than a missing statistic," Bliss added. "It represents a family searching for answers, a person disconnected from support, and a patient who may miss opportunities to participate in research or access emerging therapies. As treatments move closer to reality, identifying these individuals becomes a moral imperative."