Background: Due to extensive clinical and genetic heterogeneity of intellectual disability (ID) syndromes, the process of diagnosis is very challenging even for expert clinicians. Despite recent advancements in molecular diagnostics methodologies, a significant fraction of ID patients remains without a clinical diagnosis.
Methods, results, and conclusions: Here, in a prospective study on a cohort of 21 families (trios) with a child presenting with ID of unknown etiology, we executed phenotype-driven bioinformatic analysis method, PhenIX, utilizing targeted next-generation sequencing (NGS) data and Human Phenotype Ontology (HPO)-encoded phenotype data. This approach resulted in clinical diagnosis for eight individuals presenting with atypical manifestations of Rubinstein-Taybi syndrome 2 (MIM 613684), Spastic Paraplegia 50 (MIM 612936), Wiedemann-Steiner syndrome (MIM 605130), Cornelia de Lange syndrome 2 (MIM 300590), Cerebral creatine deficiency syndrome 1 (MIM 300352), Glass Syndrome (MIM 612313), Mental retardation, autosomal dominant 31 (MIM 616158), and Bosch-Boonstra-Schaaf optic atrophy syndrome (MIM 615722).
