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.
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet. 1983 May 21;1(8334):1151-5.
- Lo Giudice T, Lombardi F, Santorelli FM, Kawarai T, Orlacchio A. Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms. Exp Neurol. 2014 Nov;261:518-39.
- Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42(3):174-83.
- Stevanin G, Azzedine H, Denora P, Boukhris A, Tazir M et al. SPATAX consortium. Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain. 2008 Mar;131(Pt 3):772-84.