There is a spectrum of PLP1-related disorders with some genotype–phenotype correlations [4, 11–13]. Generally, patients with PLP1 missense mutations show the most severe form of PMD (connatal form), the most common PLP1 duplications result in the classical PMD, whereas deletions and null mutations in mild form of PMD and SPG2 [4, 11, 13, 14]. Epilepsy, major hypotonia, and severe psychomotor delay were constant features in our affected children and they have the same clinical history. Thus, epilepsy, not being a frequent sign in PMD, represents the specificity of this family. Considering that the majority of PLP1 point mutations cause more severe dysmyelinating diseases than null mutations, Inoue speculated that the profound dysmyelination resulting from PLP1 point mutations probably arises not from the absence of functional protein, but rather from the cytotoxic effect of mutant protein .