- 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 González-Scarano, MD
Francisco González-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 .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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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