PLP1 and Pelizeaus-Merzbacher spectrum disorder: The most common cause of hypomyelinating leukoencephalopathy is Pelizaeus-Merzbacher disease (PMD), caused by mutations in the proteolipid gene PLP1. The most common presentations of PMD include the connatal form, where symptoms are present at the time of birth, and the classical form, where symptoms develop within the first months of life.66 Symptoms begin with nystagmus, hypotonia, ataxia and head tremor.