Hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) is a group of clinically and genetically diverse disorders in which the primary symptom is insidiously progressive lower extremity weakness and spasticity. Neuropathologic studies of uncomplicated HSP reveal axonal degeneration limited to the central nervous system, particularly involving distal aspects of corticospinal and fasiculus gracilis fibers. Seventeen different genetic types of HSP have been identified. Genes have been discovered for two common forms of dominantly inherited HSP (spastin and alastin genes), one rare recessively inherited form (paraplegin gene) and two X-linked forms of HSP (L1 cell adhesion molecule and proteolipid protein). Genetic testing is available commercially for spastin gene mutations, responsible for approximately 40% of dominantly inherited HSP. The differential diagnosis of HSP includes treatable disorders as well as conditions whose prognosis differs significantly from HSP. This article summarizes clinical, pathological, and genetic features of the heredity spastic paraplegias.