Pure spastic paraplegia panel [36 genes]

Hereditary spastic paraplegia has an estimated prevalence of 1.8 in 100,000. The genetic cause is identified in 33-55% of families with autosomal dominant inheritance (AD-SP) and in 18-29% of families with autosomal recessive inheritance (AR-SP). The most frequent form of AD-SP is SPG4 (SPAST), representing 40% of AD-SP forms and 20% of sporadic cases (Ruano et al., 2014). SPG3A (ATL1) is the cause in 10-15% of AD-SP cases (up to 50% in SPF4-negative cohorts), being the most common form starting in at the first decade of life (Giudice et al., 2014). SPG11 is the most common cause of AR-SP (20-50%) (Stevanin et al., 2008).

In her historical description, Anita Harding distinguishes between pure and complex forms (Harding, 1983). Pure forms present isolated pyramid signs, such as spasticity, hyperreflexia, Babinski signs, and motor deficits, which can be associated with sphincter disorders and profound sensory alterations. Complex forms comprise diverse clinical entities that combine spastic paraplegia with other neurological/non-neurological signs such as cerebellar ataxia, optic atrophy, retinitis pigmentosa, thinning of the corpus callosum, neuropathy, or epilepsy, among others.