A female patient with paramyotonia congenita. Part 2: Contribution of SCN4A to the developing brain

SCN4A encodes the α-subunit of the voltage-gated sodium channel Na V 1.4, which is responsible for the generation of action potentials and excitation of skeletal muscle fibers. Paramyotonia congenita (PMC) is a congenital disorder characterized by non-dystrophic myotonia due to variants of SCN4A . SCN4A has been considered to be exclusively expressed in muscles, and the brain phenotype has not been reported until recently, including descriptions of essential tremor and epilepsy. The patient is a 20-year-old woman with PMC by detecting a c.3917G>A, p.(Gly1306Glu) variant in SCN4A . The patient also showed neurological symptoms, such as epilepsy, from 1 year old and intellectual disability (intelligence quotient 48). We confirmed the Na V 1.4 expression in the brain of developing mice, 10 days after birth, immunohistochemically, in the entire cerebral cortex, the olfactory bulb and the midbrain but not in the hippocampus or cerebellum. However, the Na V 1.4 expression was not detected in adult mouse cortex. Na V 1.4 was shown to be expressed in the cerebral cortex of young mice but not in adults. Since our patient had shown intellectual disability and epilepsy from infancy, Na V 1.4 was considered to be involved in the developing brain and cause central nervous system symptom in some situations.