Abstract

The hereditary spastic paraplegias (HSP) are characterized by spastic gait with weakness in the legs and additional neurological or extra-neurological signs in "complicated" forms.

The past two decades have witnessed major advances in our understanding of their molecular bases with the identification of a plethora of loci and the cloning of several SPG genes. Combined genetic and clinical information has permitted a modern, molecularly-driven classification and an improved diagnosis, with several new data on the possible disease mechanisms. Further heterogeneity will rapidly emerge with the diffusion of next-generation sequencing platforms and, under the shadow of common themes in the pathogenesis, new therapeutic options will likely emerge for a great number of patients.

Keywords: Hereditary spastic paraplegia, genetic, genotype/phenotype correlations, heterogeneity, mechanisms of disease, mutation, SPG.