National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Pelizaeus-Merzbacher disease

Información en español


Other Names:
PMD; Pelizaeus Merzbacher disease; Pelizaeus Merzbacher brain sclerosis
Categories:
This disease is grouped under:
Pelizaeus-Merzbacher disease is a disorder that affects the brain and spinal cord. It is a type of leukodystrophy and is characterized by problems with coordination, motor skills, and learning. The age of onset and the severity of the symptoms varies greatly depending on the type of disease. It is caused by an inability to form myelin due to mutations in the PLP1 gene. It is passed through families in an X-linked recessive pattern.[1] The condition primarily affects males.[1][2][3] Treatment requires a multidisciplinary team approach, with members dictated by the presenting symptoms.[3]
Last updated: 3/23/2016

Pelizaeus-Merzbacher disease is divided into classic and severe (connatal) types. Although these two types differ in severity, their symptoms can overlap.[1]

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 may improve, but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements).[1] Cognitive abilities may be impaired, but speech and language are usually present.[3]

Severe or connatal Pelizaeus-Merzbacher disease is the more severe of the two types. Symptoms are usually present at birth or develop in the first few weeks of life. Features include nystagmus, problems feeding, a whistling sound when breathing, progressive spasticity leading to joint deformities (contractures) that restrict movement, speech difficulties (dysarthria), ataxia, and seizures.[1] Children often have short stature and poor weight gain. Those affected with connatal Pelizaeus-Merzbacher disease don't walk or develop effective use of their upper limbs. Verbal expression is usually severely affected, but comprehension may be significant.[3]

Last updated: 3/23/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 52 |
Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Psychomotor deterioration 0002361
80%-99% of people have these symptoms
Abnormal pyramidal sign 0007256
Ataxia 0001251
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Cachexia
Wasting syndrome
0004326
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood
[ more ] 		0002376
Dystonia 0001332
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy
[ more ] 		0001531
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Global developmental delay 0001263
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Kyphosis
Hunched back
Round back
[ more ] 		0002808
Muscular hypotonia
Low or weak muscle tone
0001252
Optic atrophy 0000648
Premature birth
Premature delivery of affected infants
Preterm delivery
[ more ] 		0001622
Progressive spastic quadriplegia 0002478
Scoliosis 0002650
Slow progression
Signs and symptoms worsen slowly with time
0003677
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
30%-79% of people have these symptoms
Abnormality of the urinary system
Urinary tract abnormalities
Urinary tract abnormality
Urinary tract anomalies
[ more ] 		0000079
Abnormality of visual evoked potentials 0000649
Arteriovenous malformation 0100026
Bowel incontinence
Loss of bowel control
0002607
Choreoathetosis 0001266
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Dysarthria
Difficulty articulating speech
0001260
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty
[ more ] 		0002015
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Head titubation 0002599
Hearing impairment
Hearing defect
Deafness
[ more ] 		0000365
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment
[ more ] 		0002167
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
Reduction of oligodendroglia 0100709
Respiratory insufficiency
Respiratory impairment
0002093
Seizure 0001250
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Sudanophilic leukodystrophy 0003269
5%-29% of people have these symptoms
Congenital laryngeal stridor 0004886
Peripheral neuropathy 0009830
1%-4% of people have these symptoms
Hyporeflexia
Decreased reflex response
Decreased reflexes
[ more ] 		0001265
Percent of people who have these symptoms is not available through HPO
Cerebral dysmyelination 0007266
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Rotary nystagmus 0001583
Scanning speech
Explosive speech
0002168
Tremor 0001337
X-linked recessive inheritance 0001419
Showing of 52 |
Last updated: 7/1/2020
Pelizaeus-Merzbacher disease is caused by mutations in the PLP1 gene.[1][2][3] This 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.[1]

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.[1]
Last updated: 3/23/2016
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 striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.[1]

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.[1]

Individuals with a family history of Pelizaeus-Merzbacher disease may benefit from consulting with a genetics professional. This type of healthcare professional can provide information regarding genetic diagnosis, natural history, treatment, mode of inheritance, and genetic risks to other family members. Information about locating a genetics professional can be found under Healthcare Resources in the Find a Specialist section of this page.
Last updated: 3/23/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.
There is no cure for Pelizaeus-Merzbacher disease, nor is there a standard course of treatment.[2][4] Management typically involves a multidisciplinary team made of specialists in neurology, physical medicine, orthopedics, pulmonary medicine, and gastroenterology. Management tactics may include gastrostomy for individuals with severe dysphagia; antiepileptic drugs (AEDs) for seizures; and routine management of spasticity including physical therapy, exercise, medications (baclofen, diazepam, tizanidine, botulinum toxin), orthotics, and surgery for joint contractures. Individuals with scoliosis may benefit from proper wheelchair seating and physical therapy, with surgery reserved for the most severe cases. Specialized education and assessments are generally necessary, and assisted communication devices may be helpful.[3]

 

Last updated: 3/23/2016
The prognosis for those with Pelizaeus-Merzbacher disease is poor, with progressive deterioration until death.[2] Individuals affected with the severe (connatal) type may die during infancy or childhood, usually of aspiration. With attentive care, these individuals may live into the third decade or longer. Survival into the sixth or seventh decade has been observed for individuals with the classic type.[3]  
Last updated: 3/23/2016
It is estimated that between 1 in 200,000 to 1 in 500,000 people have PMD in the United states.[5]
Last updated: 9/8/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes Krabbe disease, Canavan disease, metachromatic leukodystrophy, Alexander disease, familial SPG, PMLD (see these terms), and cerebral palsy.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Pelizaeus-Merzbacher disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Pelizaeus-Merzbacher disease. This website is maintained by the National Library of Medicine.
  • Medline provides a list of resources on leukodystrophies. MedlinePlus is a Web site designed by the National Library of Medicine to help you research your health questions.
  • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Pelizaeus-Merzbacher disease. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • There is a history of Pelizaeus-Merzbacher disease in my family. I would like to learn more about this condition, including it's causes, symptoms, treatment and prognosis.  See answer

  • How rare is Pelizaeus-Merzbacher disease? See answer


  1. Pelizaeus-Merzbacher disease. Genetics Home Reference. March 2008; https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease.
  2. NINDS Pelizaeus-Merzbacher Disease Information Page. National Institute of Neurological Disorders and Stroke (NINDS). October 22, 2012; http://www.ninds.nih.gov/disorders/pelizaeus_merzbacher/pelizaeus_merzbacher.htm.
  3. Hobson G, Kamholtz J. PLP1-Related Disorders. GeneReviews. February 28, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1182/.
  4. What is Pelizaeus-Merzbacher Disease (PMD)?. Pelizaeus-Merzbacher Disease (PMD) Foundation. 2014; http://pmdfoundation.org/what-is-pmd/.
  5. Grace M Hobson, John Kamholz. PLP1-Related disorders. GeneReviews. February 28, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1182/. Accessed 9/8/2016.