Pelizaeus Merzbacher Disease in a Female due to Proteolipid Protein 1 duplication: A Case Report

Pelizaeus–Merzbacher disease (PMD) is a rare X-linked central nervous system disease involving the proteolipid protein 1 (PLP1) gene on Xq22.1. PMD patients’ commonly exhibit signs including nystagmus, hypotonia, and developmental delay. We report a female case of mild spectrum phenotypic expression of PMD attributable to a de novo Copy Number Variant (CNV) change. A two and half-year-old girl presented to our clinic with hypotonicity. She had apneic spells at birth, and was diagnosed to have nystagmus when she was 3 months old. In addition, she presented with delayed motor development including poor head control and inability to sit independently at 6 months of age, eventually standing with support at 20 months, and a prominent wide-based gait at 24 months. MRI head revealed diffuse, markedly delayed myelination, with a reduction in white matter volume. A chromosomal microarray testing indicated that patient carries an Xq22.1 q23 duplication of uncertain significance, of which the PLP1 is fully duplicated. Parental studies were normal. X-inactivation study was normal. Therefore, our case represents a phenotypic expression of PMD due to de novo mutation, a rare occurrence in a female.