DRP2 Mutation in Familial Autism Spectrum Disorder: A Case Report of 2 Consanguineous Patients

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic basis, and rare X-linked variants may contribute to its pathogenesis, particularly in consanguineous families. We present 2 pediatric cases from related Turkish families carrying a novel hemizygous DRP2 stop-gain mutation (p.Q232X). Case 1, a 5-year-old male, presented with ASD, macrocephaly, hypotonia, chronic otitis media with conductive hearing loss, and a mild demyelinating polyneuropathy confirmed electrophysiologically. Case 2, a 7-year-old male cousin, showed developmental delay, hyperactivity, bilateral cryptorchidism, and recurrent otitis media with hearing loss. Whole-exome sequencing identified the same DRP2 mutation in both patients, classified as likely pathogenic. Case 1 additionally carried heterozygous variants of uncertain significance in COL4A2 and MFN2. Multidisciplinary management included behavioral, speech, occupational, and physical therapies, as well as tympanostomy and orchiopexy. Longitudinal follow-up showed improved communication, motor function, and hearing, with stable neuropathy in Case 1. This report introduces a potentially novel role of DRP2 in ASD, extending its phenotypic spectrum beyond neuropathy, and underscores the need for further cases to define genotype-phenotype heterogeneity. Recognition of this variant is clinically relevant for genetic counseling in consanguineous populations, where risks extend beyond neuropathy to include broader neurodevelopmental outcomes.