Background: The proteolipid protein 1 (PLP1) gene encodes the two major proteins of the central nervous system (CNS) myelin: PLP and DM20. Aberrations in PLP1 gene  result in altered CNS myelination and manifest as Pelizaeus-Merzbacher disease (PMD) or spastic paraparesis type 2 (SPG2). Objective: To identify patients with a confirmed genetic defect in PLP1 and to characterize the phenotype and neuroimaging by mutation. Material and Methods: A retrospective/prospective study, analysis of clinical data and images and their relationship with the genetic defect in patients with impaired PLP synthesis. Results: 19 patients. (I) 16/19 corresponded to PMD, all affected individuals and their mothers with PLP1 gene duplication. 10 with family history of PMD. Average age of symptoms  onset  was 3 months (1-8 months).  Most frequent initial symptoms were delay in motor development, nystagmus, head tremor. Other clinical signs were global development delayed, cerebellar syndrome, bilateral pyramidal syndrome, dystonia. All neuroimaging showed diffuse hypomyelination. (II) 3/19 corresponded to SPG2, the study confirmed PLP1 gene mutation c.388C> T (p.His130Tyr) exon 3B in patient and mother. A 6 year old boy began at 7 months nystagmus, head tremor, motor development delayed, spastic paraparesis. Neuroimaging showed incomplete myelination regions. 2 cousins ​​on mother's side with spastic paraparesis. Conclusion: In our series, patients with PLP1 gene duplication exhibit PMD with symptoms and CNS´s hypomyelination more diffuse and severe. Those with a mutation in the gene expressed SPG2.