A case of GABRA5-related developmental and epileptic encephalopathy with response to a combination of antiepileptic drugs and a GABAering agent.

BACKGROUND: GABAA receptors are ligand-gated chloride channels that regulate inhibitory neurotransmission in the central nervous system. Recently, monoallelic de novo mutations in GABRA5 resulting in altered inhibitory synapses were found in three patients with developmental and epileptic encephalopathy. Patient description: We report on a four-year and six-month-old girl with epilepsy and global developmental delay. Serial head growth measurement revealed postnatal onset microcephaly. RESULTS: Magnetic resonance imaging (MRI) of the brain was normal at the age of eight months and subsequently showed a decrease in white matter volume and thin corpus callosum at the age of 3 years. Using whole-genome sequencing, we identified the fourth patient harboring a de novo missense mutation in GABRA5. Interestingly, the c.880G > C (p.V294F) affects the same position found in two of the three previously reported patients. CONCLUSION: This study suggests that the nucleotide c.880G is a mutation hotspot. Our patient also demonstrated significant seizure reduction after benzodiazepine. To our knowledge, this is the first case describing the favorable outcome of a GABAergic agent in seizure control for GABRA5-related developmental and epileptic encephalopathy.