Genotype–phenotype associations in hereditary spastic paraplegia: a systematic review and meta-analysis on 13,570 patients

Paediatric‐onset hereditary spastic paraplegias: a retrospective cohort study

“…12,17 Of note, the detected genetic variants were on different genes, as in adult HSP cohorts, as reported in the literature. 2,13,[20][21][22][23] In adult cohorts, pathogenic variants in SPG4 are most common, 2,16,20,21 while SPG3A variants prevailed in our paediatric cohort. This may reflect the fact that SPG4 pathogenic variants commonly present in later age.…”

Early‐onset hereditary spastic paraplegia: the possibility of a genetic diagnosis

“…Most of these identifications have been made within the past two decades, particularly after the advent of whole exome sequencing (WES), and they encompass all types of inheritances. 2 Over 60 genes have now been identified as causative, with the mutated gene products predicted to coalesce into a relatively small number of common cellular pathogenic themes that are guiding new therapeutic investigations. 1 Historically, HSPs have been underdiagnosed, though as genetic testing has become more affordable and widely employed, diagnostic accuracy has improved.…”

The emerging link between IP3 receptor turnover and Hereditary Spastic Paraplegia

“…Hereditary Spastic Paraplegias (HSPs) are a class of inherited neurodegenerative disorders characterized by progressive gait abnormalities due to muscle weakness and stiffness in the lower limbs, usually associated with degeneration of corticospinal tract motor neurons [1,2]. HSPs can be classified as either "uncomplicated" or "complicated": characteristic symptoms of uncomplicated HSPs are lower limb spastic weakness and urinary urgency, while complicated HSPs have additional features, such as ataxia and seizures [1,2]. These additional features often makes it difficult to differentiate complicated HSPs from other neurological diseases.…”

“…These additional features often makes it difficult to differentiate complicated HSPs from other neurological diseases. Interestingly, most uncomplicated HSPs are autosomal dominant, while most complicated HSPs are autosomal recessive, and often linked to inbreeding [1]. Currently, there are more than 80 known HSP-linked genes, but still many HSP cases are without a defined genetic cause [1,2].…”

“…Interestingly, most uncomplicated HSPs are autosomal dominant, while most complicated HSPs are autosomal recessive, and often linked to inbreeding [1]. Currently, there are more than 80 known HSP-linked genes, but still many HSP cases are without a defined genetic cause [1,2]. This situation is currently being resolved by WGSwhole genome sequencing [2].…”