Hereditary spastic paraplegias (HSPs) are a group of rare, inherited, neurological diseases characterized by broad clinical and genetic heterogeneity. Lower-limb spasticity with first motoneuron involvement is the core symptom of all HSPs. As spasticity is a syndrome and not a disease, it develops on top of other neurological signs (
ataxia,
dystonia, and
parkinsonism). Indeed, the definition of genes responsible for HSPs goes beyond the 79 identified SPG genes. In order to avoid making a catalog of the different genes involved in HSP in any way, we have chosen to focus on the HSP with
cerebellar ataxias since this is a frequent association described for several genes. This overlap leads to an intermediary group of
spastic ataxias which is actively genetically and clinically studied. The most striking example is SPG7, which is responsible for HSP or
cerebellar ataxia or both. There are no specific
therapies against HSPs, and there is a dearth of randomized trials in patients with HSP, especially on spasticity when it likely results from other mechanisms. Thus far, no gene-specific
therapy has been developed for HSP, but emerging
therapies in animal models and neurons derived from induced pluripotent stem cells are potential treatments for patients.