Pelizaeus-Merzbacher disease (PMD) is a rare genetic disorder in the family of leukodystrophies. Its frequency is 1 per 100,000 births. It is one of the hypomyelinating leukodystrophies, white matter diseases characterised by a permanent deficit of myelin in the brain.
Pelizaeus-Merzbacher disease is named after two German doctors who described it in the early twentieth century. As early as 1885, one family had five boys with involuntary oscillatory eye movement, spasticity in their limbs, very limited head and body control and delayed cognitive development. Twenty-five years later, in 1910, re-examination of the family showed that 14 members of the family had the disease, including two daughters, and that all were descended from the same relative. It was also noted at that time that the disease was never passed from father to son, which has since been known to be a characteristic of genetic diseases in which the responsible gene is carried by the X chromosome. Pelizaeus-Merzbacher disease presents in different forms depending on the age of onset of the first symptoms: a neonatal form, and a so-called “classic” form which occurs before the age of one. Two other less severe forms have been described: spastic paraplegia type 2 (which includes the recently described form, HEMS – Hypomyelination of Early Myelinating Structures) and the PLP1 null phenotype. The gene whose mutation is responsible for Pelizaeus-Merzbacher disease is the PLP1 gene which is effectively located on the X sex chromosome (at Xq22.2). For this reason, men and women report the disease differently, and the disease typically affects boys or men. This gene codes for proteolipid protein 1 (PLP1): 188 disease-causing mutations have been described to date.