Hereditary Spastic Paraplegia with Axonal Sensorimotor Polyneuropathy in a Korean Family Caused by Pathogenic Variant of KIF5A (c.611GA)

摘要

Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare neurodegenerative diseases that are characterized by progressive weakness and spasticity of the lower limbs. Spastic paraplegia 10 (SPG10) is a autosomal dominant HSP with early onset that is caused by pathogenic variants of the kinesin family member 5A gene (KIF5A) that encodes the kinesin heavy chain (KHC).1 Here we report two SPG10 patients carrying a pathogenic missense variant (c.611GA, p.Arg204Gln), which is a novel variation that has not been reported previously in Korea. The proband was a 48-year-old man who presented with leg weakness and gait disturbance manifesting as tip-toe walking that had slowly progressed over 18 years. Nerve conduction studies (NCS) were performed to evaluate his symptoms at the age of 36 years, which produced no remarkable findings. Urinary dysfunction that developed in his mid40s was the only concomitant clinical symptom upon presentation at our center. Neurologic examination revealed muscle weakness, spasticity, and brisk deep tendon reflexes in both legs without sensory symptoms or ataxia. Although he did not show relevant symptoms, NCS revealed axonal sensorimotor polyneuropathy (i.e., subclinical polyneuropathy) (Supplementary Table 1 in the online-only Data Supplement). His electromyography and spinal cord MRI findings were normal.