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Genetic and Rare Diseases Information Center (GARD)

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Pelizaeus-Merzbacher disease

Other Names for this Disease
  • Pelizaeus Merzbacher brain sclerosis
  • Pelizaeus Merzbacher disease
  • PMD
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Your 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. 

Our Answer

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What is Pelizaeus-Merzbacher disease?

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]
Last updated: 7/20/2009

What symptoms may be associated with Pelizaeus-Merzbacher disease?

Pelizaeus-Merzbacher disease is divided into classic and 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 usually stops but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements).[1]

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.[1]

Last updated: 7/20/2009

What causes Pelizaeus-Merzbacher disease?

Pelizaeus-Merzbacher disease is caused by a mutation in the gene that controls the production of a myelin protein called proteolipid protein-1 (PLP1) and a modified version (isoform) of proteolipid protein 1, called DM20.[1][2] 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: 7/20/2009

How is Pelizaeus-Merzbacher disease inherited?

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 in the Services section of the Resources page for this topic.

Last updated: 7/20/2009

How might Pelizaeus-Merzbacher disease be treated?

There is no cure for Pelizaeus-Merzbacher disease, nor is there a standard course of treatment.[2] Management typically involves a multidisciplinary team comprising 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), orthotics, and surgery for joint contractures. Individuals with scoliosis benefit from proper wheelchair seating and physical therapy; surgery may be required in severe cases. Specialized education and assessments are generally necessary, and assisted communication devices may be helpful.[3]

Last updated: 7/20/2009

What is the prognosis for individuals with Pelizaeus-Merzbacher disease?

The prognosis for those with Pelizaeus-Merzbacher disease is poor, with progressive deterioration until death.[2] Individuals affected with the connatal type may die during infancy or childhood, usually of aspiration; with attentive care, they 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: 7/20/2009