A Genetic Syndrome Linked To Autism May Be Much More Common Than We Imagined

A genetic syndrome associated with autism may be far more common than doctors previously thought. By analyzing data from nearly 180,000 people, researchers discovered that thousands of cases likely went undiagnosed, a finding that could change how these children are identified and treated.

Phelan-McDermid syndrome is a rare genetic disorder that primarily affects brain development. Individuals with this condition may experience developmental delays, intellectual disability, communication difficulties, low muscle tone, gastrointestinal issues, and, in many cases, characteristics of autism spectrum disorder.

The syndrome is caused by alterations in the SHANK3 gene, which is crucial for communication between neurons. For years, the condition was believed to be extremely rare, but a new study suggests it may be much more frequent than experts had assumed.

Researchers found that estimating the true prevalence of this syndrome is a major challenge. Many children never receive a diagnosis due to a lack of access to genetic testing, while others undergo tests that fail to detect all the alterations in the gene responsible for the disorder.

Furthermore, many families live far from specialized centers or are not even aware that there is a genetic syndrome behind the symptoms. As a result, thousands of cases may remain invisible to science and health systems.

To obtain a more accurate estimate, the team gathered information from ten research centers and genetic diagnostic laboratories, analyzing data from almost 180,000 people with autism. Then, the scientists applied several statistical adjustments to consider individuals without a diagnosis of autism, people who have never undergone genetic testing and limitations of the different tests used. This method made it possible to estimate how many people probably live with the syndrome, even without having been officially diagnosed.

The results were surprising. Previous estimates suggested that Phelan-McDermid syndrome affects between 2.5 and 10 people per million population. However, the new study indicates that it can affect around 14 people per 100,000 inhabitants, equivalent to approximately one person per 7,300. This means that the syndrome may be dozens of times more common than previously thought, remaining undiagnosed in a large number of children and adults.

This discovery has significant implications. The earlier a child receives a genetic diagnosis, the greater the chances of starting specific therapies, receiving appropriate care, and providing important information to the entire family.

Furthermore, knowing the true number of affected individuals helps governments plan healthcare services, encourages the development of new treatments, and sparks greater interest from the pharmaceutical industry in investing in research on the syndrome.

Researchers emphasize that the increase in prevalence does not mean the syndrome is becoming more common. What is changing is the scientific community's ability to identify it. As genetic testing becomes more accessible and accurate, conditions once considered extremely rare are being recognized much more frequently.

This study shows that thousands of people may be living with Phelan-McDermid syndrome without knowing it, underscoring the importance of access to genetic diagnosis for children with developmental delays or characteristics of autism.

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Prevalence of Phelan McDermid Syndrome Estimated To Be ~1:7300 Using a Multisource Model 

Tess Levy, David Lapidus, Kate Friedman, Paige Siper, Larry Glass, Liza Squires, Mary Hames, Joseph D. Buxbaum, and Alexander Kolevzon

Autism Research, e70297, 28 June 2026. 

DOI: 10.1002/aur.70297

Abstract: 

Estimating the prevalence of genetic disorders is complicated by many factors including sampling bias and differing methods of estimation. However, establishing the true prevalence of these disorders is critical for understanding disease burden, pharmacoeconomic modeling, and resource allocation for testing and care. Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder with an unknown true prevalence and previous estimates vary from 2.5–10 per million births. The study team reached out to a multitude of sources, including clinical genetic testing laboratories, research centers, and clinical centers. Sites provided the number of PMS diagnoses made out of the total number participants with autism tested at their site. Further extrapolations were made to adjust for the proportion of individuals with PMS who do not have autism, autism diagnosis age limitations, and type of genetic variant. Lastly, Centers for Disease Control estimates of autism rates were used to extrapolate to the general population. Ten sources participated and data from 179,837 autism cases were evaluated. The frequency of PMS diagnoses ranged from 1% to ~2.5%. However, the studies had different levels of sensitivity depending on the assay(s) used, and therefore raw results should not be directly compared. After applying extrapolations, including adjustments for assay sensitivity and other factors, the final weighted average was 13.7 per 100,000 (95% CI 10.02–18.60 per 100,000), indicating 1 in ~7300 individuals in the general population have PMS. We leveraged a diverse set of genetic data from multiple sources to generate a population-level estimate of the prevalence of PMS. Our findings indicate that PMS affects approximately 13.7 per 100,000 individuals, substantially higher than previous estimates.