The study estimates that Phelan-McDermid syndrome could affect about one in every 7,300 people, equivalent to around 13.7 cases per 100,000 people.
In the United States alone, the researchers estimate that more than 45,000 people could be living with the condition.
Phelan-McDermid syndrome is a genetic disorder involving the SHANK3 gene on chromosome 22.
The condition can cause a range of developmental, intellectual, medical and behavioral challenges. Most people with the syndrome also meet the criteria for autism spectrum disorder.
Changes involving SHANK3 are estimated to account for as many as 1% of autism spectrum disorder cases, according to the researchers.
To estimate the prevalence of the syndrome, the Mount Sinai team analyzed information from nearly 180,000 people with autism who had undergone genetic testing.
The researchers combined data from 10 sources, including genetic testing laboratories, hospitals and major autism research programs.
The researchers then adjusted their calculations to account for people who may have the syndrome but have not been diagnosed, limitations in genetic testing and people with Phelan-McDermid syndrome who do not meet the criteria for autism.
They said the gap between estimated and diagnosed cases may partly be explained by limited access to genetic testing.
Some people with developmental disabilities or autism may never be offered genetic testing, while some families may face insurance barriers or receive tests that do not adequately assess the SHANK3 gene.
Tess Levy, the study's first author and an assistant professor of psychiatry at the Icahn School of Medicine at Mount Sinai, said broader genetic testing could help identify people whose condition has not yet been recognized.
The findings come as researchers work on potential targeted treatments for Phelan-McDermid syndrome.
Several clinical trials are underway, including approaches designed around the biological mechanisms involved in the disorder.
Researchers say identifying people with the syndrome could become increasingly important as potential treatments advance.
A genetic diagnosis may also help families access specialized medical care, research programs, clinical trials and patient support networks.
The study, published in Autism Research, was supported by CureSHANK and Neuren Pharmaceuticals.
The researchers described it as one of the most comprehensive efforts so far to estimate the prevalence of Phelan-McDermid syndrome.
The findings suggest that the number of people living with the condition may be substantially higher than the number currently diagnosed, highlighting the importance of genetic testing in identifying previously unrecognized cases.
