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

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Epidemiology

Background:

• Estimating genetic disorder prevalence is challenging due to sampling bias and varied methodologies.
• Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder with previously uncertain prevalence, with estimates ranging from 2.5-10 per million births.
• Accurate prevalence data is crucial for understanding disease burden, pharmacoeconomics, and healthcare resource allocation.

Purpose of the Study:

• To establish a more accurate population-level prevalence estimate for Phelan-McDermid syndrome (PMS).
• To refine understanding of PMS prevalence by accounting for diagnostic factors and autism co-occurrence.

Main Methods:

• Data was collected from ten sources, including genetic testing labs and research centers, evaluating 179,837 autism cases.
• Extrapolation methods adjusted for PMS cases without autism, age limitations in autism diagnosis, genetic variant types, and assay sensitivity.
• Centers for Disease Control autism prevalence data was used to extrapolate findings to the general population.

Main Results:

• The frequency of PMS diagnoses in evaluated autism cases ranged from 1% to approximately 2.5%.
• After applying adjustments and extrapolations, the weighted average prevalence was calculated at 13.7 per 100,000 individuals (95% CI 10.02-18.60).
• This translates to an estimated prevalence of 1 in approximately 7300 individuals in the general population.

Conclusions:

• The study provides a robust population-level prevalence estimate for Phelan-McDermid syndrome.
• The findings indicate that PMS is significantly more prevalent than previously estimated.
• This revised prevalence estimate has implications for clinical awareness, diagnostic strategies, and resource planning for PMS.