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Genetics Home Reference: your guide to understanding genetic conditions
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Pelizaeus-Merzbacher disease

Reviewed March 2008

What is Pelizaeus-Merzbacher disease?

Pelizaeus-Merzbacher disease is an inherited condition involving the brain and spinal cord (central nervous system). This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by degeneration of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Pelizaeus-Merzbacher disease is caused by an inability to form myelin (dysmyelination). As a result, individuals with this condition have impaired intellectual functions, such as language and memory, and delayed motor skills, such as coordination and walking. Typically, motor skills are more severely affected than intellectual function; motor skills development tends to occur more slowly and usually stops in a person's teens, followed by gradual deterioration.

Pelizaeus-Merzbacher disease is divided into classic and connatal types. Although these two types differ in severity, their features can overlap.

Classic Pelizaeus-Merzbacher disease is the more common type. Within the first year of life, those affected with classic Pelizaeus-Merzbacher disease typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills such as crawling or walking. As the child gets older, nystagmus usually stops but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements).

Connatal Pelizaeus-Merzbacher disease is the more severe of the two types. Symptoms can begin in infancy and include problems feeding, a whistling sound when breathing, progressive spasticity leading to joint deformities (contractures) that restrict movement, speech difficulties (dysarthria), ataxia, and seizures. Those affected with connatal Pelizaeus-Merzbacher disease show little development of motor skills and intellectual function.

How common is Pelizaeus-Merzbacher disease?

The prevalence of Pelizaeus-Merzbacher disease is estimated to be 1 in 200,000 to 500,000 males in the United States. This condition rarely affects females.

What genes are related to Pelizaeus-Merzbacher disease?

Mutations in the PLP1 gene cause Pelizaeus-Merzbacher disease. The PLP1 gene provides instructions for producing proteolipid protein 1 and a modified version (isoform) of proteolipid protein 1, called DM20. Proteolipid protein 1 and DM20 are primarily located in the central nervous system and are the main proteins found in myelin, the fatty covering that insulates nerve fibers. A lack of proteolipid protein 1 and DM20 can cause dysmyelination, which can impair nervous system function, resulting in the signs and symptoms of Pelizaeus-Merzbacher disease.

It is estimated that 5 percent to 20 percent of people with Pelizaeus-Merzbacher disease do not have identified mutations in the PLP1 gene. In these cases, the cause of the condition is unknown.

Related Gene(s)

Changes in this gene are associated with Pelizaeus-Merzbacher disease.

  • PLP1

How do people inherit Pelizaeus-Merzbacher disease?

This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the gene, but generally does not experience signs and symptoms of the disorder. Some females who carry a PLP1 mutation, however, may experience muscle stiffness and a decrease in intellectual function. Females with one PLP1 mutation have an increased risk of experiencing progressive deterioration of cognitive functions (dementia) later in life.

Where can I find information about diagnosis or management of Pelizaeus-Merzbacher disease?

These resources address the diagnosis or management of Pelizaeus-Merzbacher disease and may include treatment providers.

  • Gene Review: PLP1-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1182)
  • Genetic Testing Registry: Pelizaeus-Merzbacher disease (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0205711)

You might also find information on the diagnosis or management of Pelizaeus-Merzbacher disease in Educational resources (http://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Pelizaeus-Merzbacher disease?

You may find the following resources about Pelizaeus-Merzbacher disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Pelizaeus-Merzbacher disease?

  • Cockayne-Pelizaeus-Merzbacher Disease
  • PMD
  • sclerosis; brain, Pelizaeus-Merzbacher

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Pelizaeus-Merzbacher disease?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Pelizaeus-Merzbacher disease?

ataxia ; carrier ; cell ; central nervous system ; chromosome ; dementia ; dysarthria ; gene ; hypotonia ; inheritance ; inherited ; involuntary ; joint ; motor ; muscle tone ; mutation ; nervous system ; nystagmus ; prevalence ; protein ; recessive ; sclerosis ; sex chromosomes ; spasticity ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Cailloux F, Gauthier-Barichard F, Mimault C, Isabelle V, Courtois V, Giraud G, Dastugue B, Boespflug-Tanguy O. Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease. Eur J Hum Genet. 2000 Nov;8(11):837-45. (http://www.ncbi.nlm.nih.gov/pubmed/11093273?dopt=Abstract)
  • Garbern JY. Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis. Cell Mol Life Sci. 2007 Jan;64(1):50-65. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17115121?dopt=Abstract)
  • Garbern JY. Pelizaeus-Merzbacher disease: pathogenic mechanisms and insights into the roles of proteolipid protein 1 in the nervous system. J Neurol Sci. 2005 Feb 15;228(2):201-3. Epub 2004 Dec 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15694206?dopt=Abstract)
  • Hudson LD. Pelizaeus-Merzbacher disease and spastic paraplegia type 2: two faces of myelin loss from mutations in the same gene. J Child Neurol. 2003 Sep;18(9):616-24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14572140?dopt=Abstract)
  • Inoue K, Tanaka H, Scaglia F, Araki A, Shaffer LG, Lupski JR. Compensating for central nervous system dysmyelination: females with a proteolipid protein gene duplication and sustained clinical improvement. Ann Neurol. 2001 Dec;50(6):747-54. (http://www.ncbi.nlm.nih.gov/pubmed/11761472?dopt=Abstract)
  • Inoue K. PLP1-related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Neurogenetics. 2005 Feb;6(1):1-16. Epub 2004 Dec 31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15627202?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2008
Published: December 16, 2014