Neuronal spectrinopathies. Spectrins are a major component of the neuronal cytoskeleton, the scaffold underneath the cell membrane that gives cells their characteristic shape and anchors transmembrane proteins such as voltage-gated ion channels. SPTAN1, the gene coding for the non-erythrocyte alpha-II spectrin, has been known as a rare cause of early-onset epileptic encephalopathies with hypomyelination and atrophy. However, the full phenotypic spectrum and the range of pathogenic variants was unknown. In a recent publication in Brain, 20 patients with pathogenic variants in SPTAN1 are reported, expanding the known range of phenotypes and suggesting a very unusual disease mechanism through in-frame deletions or duplications. Here is what links the neuronal cytoskeleton to epileptic encephalopathies. Continue reading →