The molecular pathogenesis of Pelizaeus-Merzbacher disease

In 1885, Pelizaeus(1) described 5 boys in a single family with nystagmus, s pastic quadriparesis, ataxia, and delay in cognitive development. In 1910, Merzbacher(2) reexamined this family, which then included 14 affected indiv iduals, including 2 girls, and found that all affected family members share d a common female ancestor. Also, he noted that the disease was passed excl usively through the female line without male-to-male transmission. Patholog ical analysis of brain tissue from one affected individual showed that most of the central white matter lacked histochemical staining for myelin, alth ough there were occasional small regions of preserved myelin, giving the se ctions a "tigroid" appearance. The description of this family provides the clinical, genetic, and pathological basis for Pelizaeus-Merzbacher disease (PMD): an X-linked disorder of myelination classically characterized by nys tagmus, spastic quadriparesis, ataxia, and cognitive delay in early childho od.