- Amy T Waldman, MD
Amy T Waldman, MD
- Assistant Professor of Child Neurology
- Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine
- Section Editors
- Francisco Gonzalez-Scarano, MD
Francisco Gonzalez-Scarano, MD
- Section Editor — Multiple Sclerosis; Neurovirology & NeuroAIDS
- John P. Howe, III, MD, Distinguished Chair in Health Policy
- The University of Texas Health Science Center at San Antonio
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
- Helen V Firth, DM, FRCP, DCH
Helen V Firth, DM, FRCP, DCH
- Section Editor — Genetics
- Consultant Clinical Geneticist
- Addenbrooke's Hospital, Cambridge, UK
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) .
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 . 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 .
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- Role of PLP1
- - Duplications
- - Missense mutations
- - Other mutations
- - Null mutations
- CLINICAL FEATURES
- Connatal PMD
- Classic PMD
- Transitional form
- X-linked spastic paraplegia type 2
- PLP1 null syndrome
- Carrier females
- Genetic testing
- DIFFERENTIAL DIAGNOSIS
- Pelizaeus-Merzbacher-like disease
- Hypomyelinating leukodystrophies
- Other leukodystrophies
- Hereditary spastic paraplegia
- SUMMARY AND RECOMMENDATIONS