Nueva variante en gen PLP1 asociada a paraplejia espástica tipo 2, ligada al X: primer reporte de una familia en Colombia

Hereditary spastic paraplegias (HSP) are genetic disorders characterized by spasticity in the lower limbs, weakness, and sensory disturbances. Global prevalence ranges from 1.27 to 9.6 per 100,000 individuals. Mutations in the PLP1 gene cause various X-linked HSP phenotypes, including Pelizaeus-Merzbacher disease and Spastic Paraplegia type 2 (SPG2).A 53-year-old male presented with chronic lower limb weakness since childhood, requiring a wheelchair at age 47 and exhibiting zero strength in the lower limbs. Magnetic resonance imaging revealed periventricular leukodystrophy, and similar symptoms were found in maternal uncles and a nephew. The 32-year-old nephew had gait difficulties. A genetic sequencing panel identified a hemizygous variant of uncertain significance in the PLP1 gene (c.197A>T (p.His66Leu)) in both, not reported in population genetic databases.X-linked SPG2 is a disease primarily affecting gait and causing lower limb weakness. Reports indicate that it may also include cognitive impairment, nystagmus, and ataxia, although in the studied family, weakness predominated without cerebellar symptoms. Thirty-six families with this condition have been documented worldwide, with cases of asymptomatic carrier females. The c.197A>T (p.His66Leu) variant in the PLP1 gene, identified in this case, is novel and, although classified as of uncertain significance, could be pathogenic according to bioinformatic predictors, explaining the SPG2 presentation in this family.