Abstracts

Rationale: GRIN2A mutations have recently been identified in 9-20% of patients with epilepsy-aphasia syndromes (EAS). GRIN2A encodes the NR2A subunit of the glutamate NMDA receptor. The speech deficits associated with GRIN2A mutations have not been studied. Here, we delineate the speech phenotype of individuals with GRIN2A-associated EAS. Methods: We studied 11 individuals from three families with GRIN2A-associated EAS. A range of tasks was performed to assess speech, oral motor skills, cognition and language. Results: Family A included 5 members with autosomal dominant rolandic epilepsy with speech dyspraxia, Family C was a father-son pair with ECSWS and Family D comprised 2 brothers with EAS, their sister with ECSWS, and their mother without a history of seizures. Median age was 48 years (mean 38 years, range 16-64 years). None of the ten individuals with epilepsy had ongoing seizures, and the majority had no epileptiform abnormalities on their most recent electroencephalogram. The GRIN2A speech phenotype consisted of a combination of speech dyspraxia and dysarthria, resulting in poor speech intelligibility in some individuals. Speech was typified by imprecise articulation of consonants and vowels (11/11, 100%) and hypernasality (7/11, 64%) with prosodic disturbance (stress errors 7/11, 64%). Oral motor skills and execution of maximum performance tasks (vowel prolongation 8/11, 73%; repetition of monosyllables 10/11, 91%; repetition of trisyllables 7/11, 64%) were also impaired. The speech phenotype was present in one individual who did not have seizures. Conclusions: Distinctive features of dysarthria and dyspraxia are found in individuals with GRIN2A EAS; dysarthria has not been previously recognized in these disorders. The phenotype was also present in the absence of seizures, suggesting that GRIN2A is an important gene underpinning motor speech function. This is an important new finding highlighting the need for precise clinical speech assessment in this group, and targeted intervention.