Pelizaeus-Merzbacher Disease

1. Pelizaeus-Merzbacher Disease The Guide To Better Understanding Your Consumers With Pelizaeus-Merzbacher Disease (PMD)

2. What Is Pmd? • Pelizaeus-Merzbacher disease is a rare, inherited, degenerative, central nervous system disorder in which coordination, motor abilities, and intellectual function deteriorate. The disease is one of a group of genetic disorders called the leukodystrophies that affect growth of the myelin sheath, the fatty covering--which acts as an insulator--on nerve fibers in the brain. • 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.

3. Common Symptoms • Symptoms in infants include: • Slow growth • Nystagmus (Involuntary jerky eye movements) • Poor head control • Symptoms in adults include: • Deteriorating speech • Tremor • Involuntary movements • Grimacing • Weakness • Unsteady gait • Muscle contractures • Spasticity • Mental deterioration • Convulsions • Skeletal deformation

4. Causes • Mutations in the PLP1 gene cause 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.

5. Causes Continued • 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.

6. Diagnosis • The diagnosis of PMD is often first suggested after identification by magnetic resonance imaging (MRI) of abnormal white matter (high T2 signal intensity, i.e. T2 lengthening) throughout the brain, which is typically evident by about 1 year of age, but more subtle abnormalities should be evident during infancy. Unless there is a family history consistent with sex-linked inheritance, the condition is often misdiagnosed as cerebral palsy. Once a PLP1 or GJA12 mutation is identified, prenatal diagnosis or preimplantation genetic diagnostic testing is possible.

7. Treatment • Treatment, which is symptomatic and supportive, may include medication for seizures and spasticity. Regular evaluations by physical medicine and rehabilitation, orthopedic, developmental and neurologic specialists should be made to ensure optimal therapy and educational resources. The prognosis for those with Pelizaeus-Merzbacher disease is highly variable, with children with the most severe, usually not surviving to adolescence, but survival into the sixth or even seventh decades is possible, especially with attentive care. Genetic counseling should be provided to the family of a child with PMD.

8. Source of Information • http://www.ninds.nih.gov/disorders/pelizaeus_merzbacher/pelizaeus_merzbacher.htm • http://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease • http://www.wrongdiagnosis.com/p/pelizaeus_merzbacher_disease/symptoms.htm • http://www.pmdfoundation.org/whatispmd.htm