The disease is one of a group of genetic disorders called the leukodystrophies that affect growth of the myelin sheath, the fatty covering--which acts as an insulator--on nerve fibers in the brain. It is caused by a usually recessive mutation of the gene on the long arm of the X-chromosome that codes for a myelin protein called proteolipid protein 1 or PLP1. There are several forms of<unk>  including classic, connatal, transitional, adult variants. Milder mutations of the PLP1 gene that mainly cause leg weakness and spasticity, with little or no cerebral involvement, are classified as spastic paraplegia 2 (SPG2).
The onset of<unk>  is usually in early infancy. The most characteristic early signs are nystagmus (rapid, involuntary, rhythmic motion of the eyes) and hypotonia (low muscle tone).  Motor abilities are delayed or never acquired, mostly depending upon the severity of the mutation. Most children with<unk>  learn to understand language, and usually have some speech. Other signs may include tremor, incoordination,  involuntary movements, weakness, unsteady gait, and over time, legs and arms may become spastic.
Muscle contractures (shrinkage or shortening of a muscle) often occur over time. Mental functions may deteriorate. Some patients may have convulsions and skeletal deformation, such as scoliosis, resulting from abnormal muscular stress on bones.
Pelizaeus-Merzbacher disease
Axenfeld syndrome
Zunich-Kaye syndrome
Hurler-Scheie syndrome
Braun-Bayer syndrome
Fox-Fordyce disease
Rajab-Spranger syndrome
Sturge-Weber syndrome