- Pelizaeus Merzbacher disease
- Pelizaeus Merzbacher brain sclerosis
Your QuestionThere 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.
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Questions on this page
- What is Pelizaeus-Merzbacher disease?
- What symptoms are the signs and symptoms of Pelizaeus-Merzbacher disease?
- What causes Pelizaeus-Merzbacher disease?
- How is Pelizaeus-Merzbacher disease inherited?
- How might Pelizaeus-Merzbacher disease be treated?
- What is the long-term outlook (prognosis) for individuals with Pelizaeus-Merzbacher disease?
Pelizaeus-Merzbacher disease is divided into classic and severe (connatal) types. Although these two types differ in severity, their symptoms 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 may improve, but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements). Cognitive abilities may be impaired, but speech and language are usually present.
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. 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.
Pelizaeus-Merzbacher disease is caused by mutations in the PLP1 gene. 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.
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.
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.
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.
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 Genetics Resources section of the Living With page for this topic.
There is no cure for Pelizaeus-Merzbacher disease, nor is there a standard course of treatment. 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.
- Pelizaeus-Merzbacher disease. Genetics Home Reference. March 2008; https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease.
- 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.
- Hobson G, Kamholtz J. PLP1-Related Disorders. GeneReviews. February 28, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1182/.
- What is Pelizaeus-Merzbacher Disease (PMD)?. Pelizaeus-Merzbacher Disease (PMD) Foundation. 2014; http://pmdfoundation.org/what-is-pmd/.