New research led by a multi-institutional team of scientists at the Seaver Autism Center for Research and Treatment at Mount Sinai suggests that Phelan-McDermid syndrome (PMS) may be much more common than earlier estimates indicated. The findings, which were recently published in the journal Autism Research, provide a new statistical framework for understanding the reach of this rare genetic condition, estimating that the disorder affects approximately 1 in 7,300 people. This revised figure represents a significant increase in the known prevalence of the syndrome and suggests that thousands of individuals may be living without a proper diagnosis.
Phelan-McDermid syndrome is a rare genetic disorder typically caused by a deletion or mutation involving the SHANK3 gene located on chromosome 22. This specific gene is critical for the development and function of synapses—the connections between brain cells that allow for communication within the nervous system. Because the SHANK3 gene plays such a fundamental role in neurological architecture, its absence or impairment can lead to a broad range of medical, intellectual, and behavioral challenges. These often include global developmental delays, absent or severely delayed speech, impaired motor skills, and various medical comorbidities such as seizures or gastrointestinal issues.
The connection between Phelan-McDermid syndrome and autism spectrum disorder (ASD) is particularly strong. Most individuals diagnosed with the syndrome also meet the clinical criteria for autism. In fact, genetic changes affecting the SHANK3 gene are believed to account for as many as one percent of all autism spectrum disorder cases globally. Despite this clear link, the syndrome has historically been classified as an ultra-rare condition, a designation that the new Mount Sinai study seeks to re-evaluate through a comprehensive analysis of modern genetic data.
Genetic Data Reveal a Much Larger Population
To estimate how common the condition may truly be, the Mount Sinai researchers spearheaded a massive collaborative effort, working alongside genetic testing laboratories, academic medical centers, and large-scale autism research programs. The scale of the study was unprecedented for this specific disorder; the team examined and analyzed genetic data from nearly 180,000 people with autism who had undergone various forms of genetic testing.
By casting such a wide net, the researchers were able to move beyond small, localized clinical samples and look at the broader landscape of neurodevelopmental genetics. Their analysis combined information from ten separate and highly reputable sources, creating a robust dataset that included contributions from GeneDx, Labcorp, and Ambry Genetics. Additionally, the study integrated data from the SPARK research study—the largest long-term study of autism in the United States—as well as the Autism Sequencing Consortium and several major children’s hospitals across the country.
The methodology required a careful balancing act. The researchers had to account for several variables that often skew prevalence data, including undiagnosed cases in the general population, the historical limits of genetic testing technologies, and the subset of people with Phelan-McDermid syndrome who do not meet the formal diagnostic criteria for autism. After applying these statistical corrections to their massive dataset, the researchers estimated a prevalence rate of 13.7 cases per 100,000 people. When translated into more common terms, that works out to approximately 1 in 7,300 individuals.
This new estimate represents a major shift from previous figures, which often characterized the syndrome as affecting only a few thousand people worldwide. Under this new model, the researchers suggest that more than 45,000 people in the United States alone could be living with Phelan-McDermid syndrome. The discrepancy between the number of currently diagnosed patients and this new estimate highlights a significant gap in the healthcare system’s ability to identify and support these individuals.
