Usher Syndrome Type 2A and Epileptic Encephalopathy with Spike-Wave Activation in Sleep: A Coincidental Dual...

USH2A-related Usher syndrome type 2A is classically characterized by congenital or early-onset sensorineural hearing loss and later-onset retinitis pigmentosa, and epilepsy is not a recognized feature of USH2A-related disease.

We report an 11-year-old boy who initially presented with nocturnal focal seizures and left occipital epileptiform discharges, followed by cognitive and academic decline and an electroencephalographic evolution consistent with developmental and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS). Brain magnetic resonance imaging, including repeat evaluation with 3-Tesla imaging, was normal. Because of known parental consanguinity and a treatment-resistant course, exome sequencing was performed and identified a homozygous pathogenic USH2A variant, USH2A(NM_206933.4):c.802G>A;p.(Gly268Arg), with heterozygous segregation in both parents. Genotype-directed evaluation confirmed bilateral moderate-to-moderately severe sensorineural hearing loss (pure tone average: right 60 dB HL; left 50 dB HL), whereas retinal involvement was not clinically evident at the time of assessment.

To our knowledge, the co-occurrence of biallelic USH2A pathogenicity and an EE-SWAS phenotype has not been reported previously. However, because the same USH2A variant has not been associated with epilepsy or EE-SWAS in the published literature, this co-occurrence is most plausibly interpreted as a coincidental dual diagnosis/dual pathology. This case is noteworthy because it illustrates that exome sequencing may uncover unexpected but clinically actionable syndromic diagnoses and guide targeted audiologic and ophthalmologic surveillance planning, even when the presenting phenotype is primarily neurologic.