Introduction and classification

Inherited disorders in which the predominant clinical syndrome is gait disturbance due to lower extremity spastic weakness are referred to collectively as the hereditary spastic paraplegias (HSPs). The various types of HSP are classified clinically according to the mode of inheritance (dominant, recessive, and X-linked); and whether lower extremity spasticity and weakness and often urinary urgency and subtle dorsal column impairment occur alone (“uncomplicated HSP”), or are accompanied by additional neurologic or systemic symptoms for which alternative causes are excluded (“complicated HSP”) (Harding, 1983).

There are at least 20 genetically distinct types of HSP (Table 53.1) including ten dominant, seven recessive, and three X-linked HSP syndromes. Eight of these HSP syndromes are “uncomplicated;” eight of these are “complicated” by the presence of additional neurologic signs; and four of these may present as either “uncomplicated” or “complicated” HSP syndromes. For some of these latter syndromes, both “uncomplicated” and “complicated” HSP phenotypes may coexist even in the same family (Table 53.1).

It is important to recognize that the HSPs are classified clinically, rather than on the basis of subclinical involvement or neuropathologic findings. Certainly, lower extremity spastic weakness may be an important feature of many other disorders, both inherited and apparently sporadic including such diverse disorders as amyotrophic lateral sclerosis, Friedreich's ataxia (Berciano et al., 2002; Ragno et al., 1977), Machado Joseph disease (spinocerebellar ataxia type 3), Charlevoix–Sanguenay syndrome (Engert et al., 2000), primary lateral sclerosis, and familial Alzheimer's disease due to presenilin 1 mutation (Brooks et al., 2003; Assini et al., 2003; Tabira et al., 2002).