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Disease Profile

Pelizaeus-Merzbacher disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

All ages

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ICD-10

E75.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

PMD; Pelizaeus Merzbacher disease; Pelizaeus Merzbacher brain sclerosis

Categories

Eye diseases; Nervous System Diseases

Summary

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]

Symptoms

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]

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.

Cause

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]

Diagnosis

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.

    Treatment

    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]

     

    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
    Deafness
    Hearing defect

    [ 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
    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.

    Organizations

    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

      Organizations Providing General Support

        Learn more

        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

        • 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.
        • Genetics Home Reference (GHR) contains information on Pelizaeus-Merzbacher disease. This website is maintained by the National Library of Medicine.
        • 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.

            References

            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; https://www.ninds.nih.gov/disorders/pelizaeus_merzbacher/pelizaeus_merzbacher.htm.
            3. Hobson G, Kamholtz J. PLP1-Related Disorders. GeneReviews. February 28, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1182/.
            4. What is Pelizaeus-Merzbacher Disease (PMD)?. Pelizaeus-Merzbacher Disease (PMD) Foundation. 2014; https://pmdfoundation.org/what-is-pmd/.
            5. Grace M Hobson, John Kamholz. PLP1-Related disorders. GeneReviews. February 28, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1182/. Accessed 9/8/2016.

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