Genetics of Hereditary Spastic Paraplegias (HSP)

Abstract

Hereditary spastic paraplegias (HSP) are a group of degenerative disorders of the spinal cord that lead to a progressive spastic gait disturbance marked by lower limb spasticity and weakness. Genetically, HSPs are among the most heterogeneous Mendelian diseases and can be inherited following autosomal dominant, autosomal recessive, and X-chromosomal modes of inheritance. More than 80 genes and gene loci have been identifi ed so far and require next-generation sequencing approaches for comprehensive genetic testing. In this chapter we discuss clinical aspects of HSP including differential diagnostics, typical presentation of common HSPs, limitations of genotype-phenotype correlation, and overlap with genetic disorders that cause progressive spasticity but are not categorized as HSPlike spastic ataxias, slow variants of amyotrophic lateral sclerosis, spastic variants of peripheral neuropathies, and adult-onset variants of leukodystrophies. In consideration of the complexity of this fi eld, we propose an algorithm for a time-and costeffi cient strategy for genetic diagnostics in HSP.

Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population

“…Thus, each type of HSP is named as SPG (spastic paraplegia gene) followed by the number representing the chronological order of identification of the genetic locus. Transmission may be recessive, dominant, X-linked or mitochondrial 8,9,10 .…”