In 1885, Friedrich Pelizaeus first identified a genetic disorder causing spasticity and developmental delay [1,2]. Twenty-five years later, Ludwig Merzbacher further described the neuropathology of 12 affected individuals related to the proband [3-6]. Together, Pelizaeus and Merzbacher identified the X-linked inheritance, the neonatal features, and the hypomyelination of the central nervous system that characterize the disease.
Pelizaeus-Merzbacher disease (PMD; MIM 312080) is classified as a dysmyelinating disorder, in which normal myelination never occurs, as opposed to a demyelinating disorder, in which normal myelin is later destroyed [7,8].
It is now recognized that PMD and subtype called X-linked spastic paraplegia type 2 (SPG2; MIM 312920) are caused by mutations of the gene for proteolipid protein (PLP1; MIM 300401) .
This topic will review the pathogenesis, clinical features, and diagnosis of PMD and related disorders.
Mutations of the proteolipid protein 1 gene (PLP1) result in a range of phenotypes that form a clinical spectrum, from the more severe Pelizaeus-Merzbacher disease (PMD) at one end, to the relatively mild X-linked spastic paraplegia 2 (SPG2) at the other . Over 160 mutations of the PLP1 gene, which is located on the long arm of the X chromosome (Xq22.2), have been identified in PMD .