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

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.