Challenges and Controversies in the Genetic Diagnosis of Hereditary Spastic Paraplegia

Curr Neurol Neurosci Rep. 2021 Feb 28;21(4):15. doi: 10.1007/s11910-021-01099-x.


Purpose of review: The hereditary spastic paraplegias (HSPs) are a group of disorders characterised by progressive lower limb weakness and spasticity. We address the challenges and controversies involved in the genetic diagnosis of HSP.

Recent findings: There is a large and rapidly expanding list of genes implicated in HSP, making it difficult to keep gene testing panels updated. There is also a high degree of phenotypic overlap between HSP and other disorders, leading to problems in choosing the right panel to analyse. We discuss genetic testing strategies for overcoming these diagnostic hurdles, including the use of targeted sequencing gene panels, whole-exome sequencing and whole-genome sequencing. Personalised treatments for HSP are on the horizon, and a genetic diagnosis may hold the key to access these treatments. Developing strategies to overcome the challenges and controversies in HSP may hold the key to a rapid and accurate genetic diagnosis.

Keywords: Diagnosis; Genetics; HSP; Hereditary spastic paraplegia; Whole-exome sequencing; Whole-genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Exome Sequencing
  • Genetic Testing
  • Humans
  • Mutation / genetics
  • Spastic Paraplegia, Hereditary* / diagnosis
  • Spastic Paraplegia, Hereditary* / genetics