chapter  12
30 Pages

Hereditary Spastic Paraplegia

ByKleopas A. Kleopa

Hereditary spastic paraplegia (HSP) encompasses a heterogeneous group of disorders characterized by progressive lower limb spasticity that were first described by Stru¨mpell, Lorrain, and Seeligmu¨ller in the late nineteenth century. Autosomal dominant (AD), autosomal recessive (AR), and X-linked inheritance of HSP have been characterized, as have early and late onset forms of HSP, as well as uncomplicated and complicated HSP phenotypes (1,2), with considerable intrafamilial variation in the age of onset and severity (3-7). The discovery of the molecular genetic mechanisms underlying many forms of HSP in the last decade has provided the basis for a new classification scheme according to genes and loci for these disorders. At least 10 loci for dominant forms, 11 loci for recessive forms, and 3 loci for X-linked HSP have been identified along with an increasing number of causative genes (Table 1). These discoveries provide an insight into the neurobiology of these disorders.

CLINICAL AND PATHOLOGICAL FEATURES OF HSP