A new case of developmental and epileptic encephalopathy and macrocytic anemia with stretched-activated ion channel TMEM63B variant

TMEM63B encodes a stretch-activated ion channel that mediates cation currents in response to osmotic and mechanical stresses. Heterozygous TMEM63B variants have recently been reported in patients with developmental and epileptic encephalopathies and progressive neurodegeneration. Here, we report a patient with a TMEM63B variant whose seizures were temporarily controlled using ketogenic diet (KD) therapy and perampanel (PER). A 2-year-old female toddler showed early-onset seizures, severe global developmental delay, quadriparesis, nystagmus, central visual impairment, and macrocytic anemia. Brain magnetic resonance imaging revealed a thin corpus callosum, delayed myelination, and progressive cerebral and cerebellar atrophy. Exome sequencing identified a de novo heterozygous variant of TMEM63B (NM_018426.3:c.130G>A, p.(Val44Met)), which was classified as pathogenic. Although most patients with TMEM63B variants have drug-resistant seizures, our patient showed temporary seizure control after administering KD and PER. This combination treatment may be effective for treating seizures in patients with the TMEM63B variant.