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Pelizaeus-Merzbacher disease

Amy T Waldman, MD
Section Editors
Francisco González-Scarano, MD
Marc C Patterson, MD, FRACP
Helen V Firth, DM, FRCP, DCH
Deputy Editor
John F Dashe, MD, PhD


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 or hypomyelinating 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 1 (PLP1; MIM 300401) [9].

This topic will review the pathogenesis, clinical features, and diagnosis of PMD and related disorders.


Mutations of the proteolipid protein 1 (PLP1) gene result in a range of phenotypes that form a clinical spectrum, from the more severe PMD at one end, to the relatively mild X-linked spastic paraplegia type 2 (SPG2) at the other [9]. 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 [9].

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Literature review current through: Oct 2017. | This topic last updated: Dec 16, 2016.
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