Chapter 17 Hereditary spastic paraparesis

Abstract

Publisher Summary Hereditary spastic paraparesis (HSP) represents a group of conditions in which the prominent feature is a progressive spastic paraparesis. The most useful way of classifying HSP is genetically to one of the current HSP gene loci. There are currently 28 spastic paraplegia (SPG) loci. Advances in recent years identifying the genes at 11 of these loci have suggested that disruption in any of the following—axonal transport, cytoskeleton regulation, mitochondrial function, myelin maintenance and assembly, and neuronal migration—may cause axonal damage in HSP. The major neuropathological feature of pure HSP is a length dependent axonopathy within the central nervous system (CNS). HSP can also be classified clinically according to the mode of inheritance, age of onset, or clinical phenotype. HSP is inherited most often as an autosomal dominant trait, with autosomal recessive and X-linked inheritance occurring rarely and very rarely, respectively. Identifying the mode of inheritance is complicated by an increasing recognition of reduced penetrance, most often described in spastin-related HSP. Two broad HSP phenotypes—pure HSP and complicated HSP—have been used to clinically classify HSP.