Abstract
Early infantile epileptic encephalopathy (EIEE) is an age-dependent epileptic encephalopathy. It occurs early in life with various types of seizures, especially tonic spasms and its overall prognosis is poor. We report a 5-year-old boy with EIEE, severe developmental delay, intractable epilepsy, and congenital cerebellar ataxia. His infantile spasms were treated successfully with ACTH, but he later developed intractable focal seizures. Whole exome sequencing revealed a maternally inherited missense mutation in the ATP2B3 gene (c.3338C > T/p.T1113M) and a de novo missense mutation in the GNAO1 gene (c.133G > C/p.G45R). Both genes are associated with calcium signaling pathways. The ATP2B3 gene is associated with intracellular calcium clearance, resulting in abnormal calcium homeostasis and X-linked spinocerebellar ataxia-1. The GNAO1 gene is associated with G protein signaling, affecting calcium signaling, and EIEE. Both mutations are related to maintain cellular calcium homeostasis, but the phenotype was not significantly more severe than those which have been reported.
Keywords
GNAO1 - ATP2B3 - early infantile epileptic encephalopathy
