Background

Although Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2 are nosologically distinguished, they are at opposite ends of a clinical spectrum of X-linked diseases caused by mutations of the same gene, the proteolipid protein 1 (PLP1) gene, and result in defective central nervous system (CNS) myelination T2-weighted magnetic resonance imaging (MRI) scan of a child aged 10 months with duplication of the proteolipid protein (PLP) gene; note the high-intensity signal throughout the cerebral white matter. Clinical signs usually include some combination of nystagmus, stridor, spastic quadriparesis, hypotonia, cognitive impairment, ataxia, tremor, and diffuse leukoencephalopathy on magnetic resonance imaging (MRI). Seizures and perinatal stridor are rare signs and are typically seen only in the most severe cases.

Duplications
(This is What I have, a duplication)

Approximately 60-70% of cases of Pelizaeus-Merzbacher disease result from duplications of the region of the X chromosome that contains PLP1 (caused, it has been proposed, by defective deoxyribonucleic acid [DNA] replication). The extent and breakpoints of duplications vary among different families. Inclusion of other genes in the duplicated region, or inclusion of aberrations of genes at the duplication endpoints, may potentially affect the phenotype. Most individuals with PLP1 duplications present with classic Pelizaeus-Merzbacher disease, typified by nystagmus that begins in the first year of life, delayed motor and cognitive milestones, and ataxia. Most of these patients acquire some language function, which can be quite good (although slow).

Epidemiology

The frequency of Pelizaeus-Merzbacher disease in the United States is not known with certainty, but the estimated prevalence is at least 1 case per 500,000 population. However, this is a conservative estimate. Internationally, the frequency of the condition is estimated to be 1 case per 100,000-1,000,000 population.

Prognosis

Individuals with connatal Pelizaeus-Merzbacher disease typically die of respiratory complications during childhood, but with attentive care, they can live into the third decade of life. Patients with classic Pelizaeus-Merzbacher disease (such as that caused by PLP1 gene duplications) can live into the fifth or sixth decade of life.

Each form of Pelizaeus-Merzbacher disease may have real or apparent intervals of stability, but the overall the trend is gradual progression. As discussed below, heterozygous females who carry a severe mutation are usually healthy, but those who carry a relatively mild mutation may develop neurologic signs, including spastic paraparesis and dementia, that typically manifest during adulthood. Respiratory difficulty and stridor can be severe enough in infants with connatal disease to require the use of a tracheostomy or other airway protection. As the child grows older, the need for such measures may lessen. Orthopedic complications are common in Pelizaeus-Merzbacher disease (PMD). Joint contractures are common in the legs and, to a lesser extent, the arms. Scoliosis can be severe enough to cause restrictive lung disease. Regular physical medicine evaluations, bracing, and physical therapy, as well as other treatments for spasticity, may reduce
or delay the need for surgical therapy. Dysphagia in Pelizaeus-Merzbacher disease can be severe enough to necessitate consideration of feeding tube placement.

Treatments

No specific treatment for Pelizaeus-Merzbacher disease is known. Medical therapy is limited to supportive care, such as the use of physical therapy, orthotics, and antispasticity agents, including intrathecal baclofen. Regular physical medicine or orthopedic evaluations, physical therapy, and careful attention to posture and seating can help to minimize the development of joint contractures, dislocations, and kyphoscoliosis.

Activity

Within their capabilities, patients should be encouraged to be active for their physical and emotional well-being. A physiatrist or physical therapist can be helpful in providing guidelines for a specific child. Aquatic therapy can be a helpful exercise to maintain leg strength, as well as an enjoyable form of recreation.

All information on this page came from the PMD page on
www.medscape.com