Pelizaeus-Merzbacher Disease

Pelizaeus-Merzbacher disease (PMD) is a demyelinating disorder of the CNS belonging to the group of hypomyelinating leukodystrophies. The disease was named in honor of Friederich Pelizaeus, a German physician, and Ludwig Merzbacher, a German pathologist. Pelizaeus discovered PMD in 1885 when he came across a family that had several male individuals with nystagmus, spastic paresis, ataxia, and developmental delay. Twenty-five years later, Merzbacher proved that the mode of inheritance of PMD was X-linked recessive. PMD occurs due to several types of mutations at the level of proteolipid protein 1 (PLP1) gene, leading to varying clinical pictures in terms of severity. The different forms of PMD, resulting from different mutations, exist on a clinical spectrum ranging between the most severe, the connatal form and spastic paraplegia type 2 (SPG2), the mildest version, with the classic form falling in between the others. SPG2 is further classified into complicated and pure types, the details of which will be explained throughout the review. PLP-1 null syndrome is a mild version of PMD described as a separate entity since its causative mutation leads to peripheral nervous system demyelination, unlike typical PMD. Since there are several types of hypomyelinating leukodystrophies (HLD) apart from PMD, PMD was classified as prototypic HLD type 1 (HLD1) to distinguish it from others that might be presenting with very similar pictures. Another disease, known as Pelizaeus-Merzbacher-Like disease (PMLD), was classified as HLD2. It is described as a separate entity from PMD due to a mutation at the level of a different gene, GJC2. This review will shed light on PMD; however, given the proximity of their clinical presentations, differentiating points will be mentioned.