Genetic and clinical characterization of SPG10: a case series of novel pathogenic variants and phenotypic diversity

KIF5A, a kinesin family protein, plays a crucial role in intracellular transport in nerve cells. Pathogenic variants in KIF5A, such as those causing SPG10, lead to corticospinal tract degeneration, resulting in hereditary spastic paraplegia (HSP). This case series highlights a novel KIF5A variant and its clinical significance in three Greek siblings with SPG10.

Three siblings with progressive gait spasticity and neurological features underwent comprehensive diagnostic evaluations, including MRI, nerve conduction studies, and genetic testing. Whole exome sequencing followed by Sanger validation identified a novel KIF5A variant (c.604C>G; p.Ser202Gly). Management strategies involved physiotherapy, occupational therapy, and Baclofen for spasticity.

Symptom progression was observed in two siblings, while one remained stable during follow-up. Cervical spondylosis and neuropathy were noted in all cases. The identified variant disrupts microtubule dynamics, contributing to corticospinal tract degeneration.

This is the first documented case series of SPG10 associated with a novel KIF5A variant in Greece. It underscores the importance of genetic testing for accurate diagnosis and highlights the need for continued research into SPG10 pathophysiology and targeted treatments.