Estimating the Prevalence of De Novo Monogenic Neurodevelopmental Disorders from Large Cohort Studies

Rare diseases impact up to 400 million individuals globally. Of the thousands of known rare diseases, many are rare neurodevelopmental disorders (RNDDs) impacting children. RNDDs have proven to be difficult to assess epidemiologically for several reasons. The rarity of them makes it difficult to observe them in the population, there is clinical overlap among many disorders, making it difficult to assess the prevalence without genetic testing, and data have yet to be available to have accurate counts of cases. Here, we utilized large sequencing cohorts of individuals with rare, de novo monogenic disorders to estimate the prevalence of variation in over 11,000 genes among cohorts with developmental delay, autism spectrum disorder, and/or epilepsy. We found that the prevalence of many RNDDs is positively correlated to the previously estimated incidence. We identified the most often mutated genes among neurodevelopmental disorders broadly, as well as developmental delay and autism spectrum disorder independently. Finally, we assessed if social media group member numbers may be a valuable way to estimate prevalence. These data are critical for individuals and families impacted by these RNDDs, clinicians and geneticists in their understanding of how common diseases are, and for researchers to potentially prioritize research into particular genes or gene sets.