Pelizaeus-Merzbacher disease in a manifesting female carrier with a PLP1 frameshift variant: neuroimaging and neurophysiological findings

Abstract

Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused by pathogenic variants in the proteolipid protein 1 (PLP1) gene. Although typically affecting males, heterozygous females may occasionally develop neurological manifestations. We report a 25-year-old female with childhood-onset gait disturbance and progressive motor impairment. Brain magnetic resonance imaging showed diffuse hypomyelination and multi-modal evoked-potential studies demonstrated widespread central conduction delay. Genetic testing identified a pathogenic PLP1 frameshift variant (c.354_355del, p.Gly120ProfsTer83).