History

In 1885, a German physician named Pelizaeus described five boys in a single family with involuntary oscillatory eye movement, spasticity in the limbs, very limited head and trunk control, and delay in cognitive development. In 1910, another German physician named Merzbacher reexamined this family, which then included 14 affected individuals including two girls, and found that all affected family members shared a common female ancestor. In addition, he noted that the disease was passed exclusively through the female line without father-to-son transmission. Pathological analysis of brain tissue from one affected individual showed that most of the central white matter generally lacked histochemical staining for myelin, the fat and protein based substance that acts as an insulator for nerve conductors in the Central Nervous System (CNS). The description of this family provides the clinical, genetic and pathological basis for Pelizaeus-Merzbacher Disease (PMD): an X-linked disorder of myelin classically characterized by nystagmus, spastic quadriparesis, ataxia and cognitive delay in early childhood.