Clinical Information

Hereditary spastic paraplegias (HSP) are a group of neurodegenerative disorders characterized by progressive lower extremity weakness and spasticity, both of which can be variable. Other common neurological symptoms include ataxia, cognitive impairment, neuropathy, seizures, and dysarthria. If onset of symptoms occurs in very early childhood, symptoms may be nonprogressive and resemble spastic digenic cerebral palsy. If the onset of symptoms occurs in later childhood or after, symptoms usually progress slowly and steadily.

Clinically HSP are classified in an uncomplicated or pure form and a complicated or complex form. The uncomplicated form presents with progressive lower-extremity spastic weakness, corticospinal tract signs, variable hypertonic urinary bladder disturbance, and disturbance in vibration sense and proprioception. The complicated form is characterized by the impairments present in uncomplicated HSP plus other system involvement or other neurologic findings. Additionally, the complicated form usually follows an autosomal recessive inheritance pattern, while the uncomplicated form predominantly follows an autosomal dominant inheritance pattern.

Given HSP are a heterogeneous group of disorders, multigene panels can be an efficient and cost-effective way to establish a molecular diagnosis for symptomatic individuals.