Genetics of hereditary spastic paraplegias

Semin Neurol. 2011 Nov;31(5):484-93. doi: 10.1055/s-0031-1299787. Epub 2012 Jan 21.


Hereditary spastic paraplegias (HSPs) are clinically and genetically highly heterogeneous. The key symptom of spastic paraparesis of lower limbs can be complicated by a variety of signs and symptoms including cognitive impairment, optic atrophy, cerebellar ataxia, peripheral nerve involvement, or seizures. At least 48 loci have been identified, termed SPG1-SPG48. Ten genes for autosomal dominant HSP are currently known, SPG4 being by far the most common subtype accounting for ∼50% of cases. SPG3 is especially common in young-onset cases. Autosomal recessive HSP seems to be even more heterogeneous. The known 12 autosomal recessive HSP genes collectively explain about one third of cases only. The most common causes for pure autosomal recessive HSP are SPG7 and SPG5. Mental retardation and thin corpus callosum on magnetic resonance imaging point toward SPG11 and SPG15. The authors provide an overview on clinical, neurophysiologic, and neuroradiologic characteristics of the more common HSP subtypes. More details are given in the tables for quick reference, and a genetic testing strategy is proposed.

Publication types

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

MeSH terms

  • Agenesis of Corpus Callosum / genetics
  • Genes, Dominant / physiology*
  • Genes, Recessive / physiology*
  • Genes, X-Linked / physiology*
  • Genetic Association Studies
  • Genetic Diseases, X-Linked
  • Genetic Testing / methods
  • Humans
  • Intellectual Disability / genetics
  • Mutation
  • Spastic Paraplegia, Hereditary / genetics*

Supplementary concepts

  • MASA (Mental Retardation, Aphasia, Shuffling Gait, Adducted Thumbs) Syndrome