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.