Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks

Abstract

Hereditary spastic paraplegia comprises a wide and heterogeneous group of inherited neurodegenerative and neurodevelopmental disorders resulting from primary retrograde dysfunction of the long descending fibers of the corticospinal tract. Although spastic paraparesis and urinary dysfunction represent the most common clinical presentation, a complex group of different neurological and systemic compromise has been recognized recently and a growing number of new genetic subtypes were described in the last decade. Clinical characterization of individual and familial history represents the main step during diagnostic workup; however, frequently, few and unspecific data allows a low rate of definite diagnosis based solely in clinical and neuroimaging basis. Likewise, a wide group of neurological acquired and inherited disorders should be included in the differential diagnosis and properly excluded after a complete laboratorial, neuroimaging, and genetic evaluation. The aim of this review article is to provide an extensive overview regarding the main clinical and genetic features of the classical and recently described subtypes of hereditary spastic paraplegia (HSP).

A novel mutation in KIF5A in a Malian family with spastic paraplegia and sensory loss

“…More than 90 HSP‐related genes (SPG1‐78, plus others) have been reported worldwide, and mutations in about 60 identified genes have been associated with these clinical variants 5. However, reports of genetically confirmed HSPs in the African population are scant and involve a limited number of these genes, mostly recessive forms 6.…”

Multigeneration family with dominant SPG30 hereditary spastic paraplegia

“…The HSPs are a group of progressive gait disorders characterized by lower extremity spasticity in their “pure” form, along with cognitive symptoms, optic atrophy, and other neurologic findings in their “complex” form. They are among the most genetically diverse neurologic disorders, with almost 90 distinct genetic loci (SPG1‐78, plus others) 8. Although >60 HSP genes within these loci have been identified, a relatively small number of common cellular pathogenic themes have emerged, among them is the disruption of the proper morphology and distribution of organelles within the long axons of corticospinal neurons 9.…”

Clinical and genetic characterization of a cohort of Chinese patients with hereditary spastic paraplegia

“…Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurologic disorders and is classified as pure HSP or complex HSP clinically. To date, more than 70 genes or loci have been linked to HSP, with autosomal dominant, autosomal recessive, X‐linked, or mitochondrial maternal transmission . Here, we collected 18 Chinese HSP pedigrees and performed genetic investigations.…”