Hereditary spastic paraplegia in three siblings with distinct genetic mutations

Hereditary spastic paraplegia is characterized by progressive motor features, including spastic gait and lower limb weakness, and encompasses numerous genetic subtypes. We report a family of six siblings born to asymptomatic consanguineous parents, in which three siblings exhibited overlapping spastic paraplegia phenotypes with developmental delay. The index patient demonstrated significant lower limb weakness and spasticity despite multiple orthopedic interventions. Next-generation sequencing identified a homozygous SELENOI c.797C > T (p.Pro266Leu) variant of uncertain significance, interpreted cautiously in the context of his SPG81-like phenotype. His older sister reportedly harbored a homozygous LAMA1 c.4579C > T (p.Gln1527Ter) variant consistent with Poretti-Boltshauser syndrome, explaining her cerebellar ataxia and nonprogressive course. His younger brother carried the same homozygous SELENOI variant as the index patient together with a de novo SATB2 c.860C > T (p.Pro287Leu) variant of uncertain significance, which was interpreted as a possible contributor to his mixed neurodevelopmental presentation. This report highlights that siblings presenting with similar early-onset spastic gait phenotypes may have distinct underlying genetic findings, supporting the value of comprehensive genetic evaluation even within a single family.