Pelizaeus-Merzbacher Disease is one of a class of neurological diseases known as leukodystrophies, disorders that affect the formation of the myelin sheath, the fat and protein covering–which acts as an insulator–on neural fibers (axons) in the central nervous system or CNS, which is the brain and spinal cord. It is a rare condition caused by mutations affecting the gene for the proteolipid protein (PLP). The PLP gene lies on the X chromosome so that most affected individuals are males who inherit the mutant or abnormal gene from their mothers. Rarely, females can have symptoms. Clinically, Pelizaeus-Merzbacher disease usually begins during infancy and signs of the disease may be present at birth or in the first few weeks of life. The first recognizable sign is a form of involuntary oscillatory movements of the eyes called nystagmus. Some infants have stridor (labored and noisy breathing). Infants may show hypotonia (lack of muscle tone; floppiness) or eventually develop spasticity (a type of increased muscle tone or stiffness of the muscles and joints). Motor and intellectual milestones are delayed, however the intellectual delay is often more apparent than real, if care and time are taken to evaluate the children. Children are often non-verbal. Head and trunk control may be impaired and wavering or tremor of the upper body when sitting is commonly seen (titubation). Seizures occur only rarely in affected children.
The clinical diagnosis generally includes the clinical findings listed above along with a family history consistent with X chromosome transmission (that is, being passed down by mothers, and never being passed from an affected father to his son). The most useful screening test after the neurologic examination and family history, is a brain magnetic resonance imaging (MRI) scan, which is a very sensitive test for leukodystrophies (diseases of the white matter), as long as it is done after one or two years of age (the times when the major white matter pathways in the brain are developing). The definitive test is demonstration of a pathologic mutation of the PLP gene.