Spastic paraparesis [107 genes]

Anita Harding’s landmark description of paraparesis distinguishes pure and complicated forms (Harding, 1983). Pure forms present isolated pyramidal signs such as spasticity, hyperreflexia, Babinski sign and motor deficits, which may be associated with sphincter disorders and alteration of deep sensitivity. Complicated forms include various clinical entities that combine spastic paraparesis with other neurological/non-neurological signs such as cerebellar ataxia, optic atrophy, retinitis pigmentosa, narrowing of the corpus callosum, neuropathy or epilepsy, among others.

Hereditary spastic paraparesis has an estimated prevalence of 1.8/100,000. The genetic cause is identified in 33-55% of families with autosomal dominant inheritance (PE-AD) and 18-29% of families with autosomal recessive inheritance (PE-AR). The most common form of PE-AD is SPG4 (SPAST), representing 40% of PE-AD forms and 20% of sporadic cases (Ruano et al., 2014). SPG3A (ATL1) is the cause of 10-15% of PE-AD cases (up to 40% in SPG4-negative cohorts), being the most frequent form of onset in the first decade (Giudice et al., 2014). SPG11 is the most common cause of PE-AR (20-50%) (Stevanin et al., 2008).

Diagnosis, prognosis and genetic counseling in affected patients and family members.

Patients with clinical suspicion of paraparesis.