Diagnostic findings and yield of investigations for children with developmental regression

Childhood conditions that feature developmental regression are poorly understood. Phenotype-genotype characterization and diagnostic yield data are needed to inform clinical decision-making. The aim of this study was to report the conditions featuring developmental regression and assess diagnostic yields of investigations. A retrospective chart review of children presenting with developmental regression to a tertiary pediatric genetic clinic between 2018 and 2021 was performed. Of 99 children, 30% (n = 30) had intellectual disability (ID), 21% (n = 21) were autistic, 39% (n = 39) were autistic with ID, and 9% (n = 9) did not have ID or autism. Thirty-two percent (n = 32) of children received a new diagnosis, including eight molecular findings not previously reported to feature developmental regression. Of the children investigated, exome sequencing (ES) provided the highest diagnostic yield (51.1%, n = 24/47), highest (63.6%, n = 14/22) for children with ID, 50% for autistic children with ID (n = 6/12) and children without autism or ID (n = 3/6), and 14.3% (n = 1/7) for autistic children without ID. We highlight the conditions that feature developmental regression and report on novel phenotypic expansions. The high diagnostic yield of ES, regardless of autism or ID diagnosis, indicates the presence of developmental regression as an opportunity to identify the cause, including for genetic differences not previously reported to include regression.