Hereditary Spastic Paraplegia

  • Alice B. SchindlerEmail author


Hereditary spastic paraplegia (HSP) refers to a group of inherited disorders characterized by the loss of upper motor neurons, resulting in progressive, lower limb spasticity and weakness. HSPs are classified as pure/uncomplicated or complicated, and vary in symptoms, severity, age of onset, and genetic etiology. Over 50 loci have been associated with the HSPs and include autosomal dominant, autosomal recessive, and X-linked genes. Genetic counseling is complicated by inter- and intra-familial variability, incomplete penetrance, and de novo mutations. This chapter reviews the different types of HSPs and how best to counsel for genetic testing.


Genetic Counselor Lower Motor Neuron Hereditary Spastic Paraplegia Spinal Cord Tumor Autosomal Recessive 
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Hereditary spastic paraplegia (HSP) (MOV 397187 kb)


  1. 1.
    Harding, A. E. (1983). Classification of the hereditary ataxias and paraplegias. Lancet, 1(8334), 1151–1155.PubMedCrossRefGoogle Scholar
  2. 2.
    Blackstone, C. (2012). Cellular pathways of hereditary spastic paraplegia. Annual Review of Neuroscience, 35, 25–47.PubMedCrossRefGoogle Scholar
  3. 3.
    McMonagle, P., Webb, S., & Hutchinson, M. (2002). The prevalence of “pure” autosomal dominant hereditary spastic paraparesis in the island of Ireland. Journal of Neurology, Neurosurgery, and Psychiatry, 72(1), 43–46.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Orlacchio, A., Kawarai, T., Totaro, A., Errico, A., St George-Hyslop, P. H., Rugarli, E. I., et al. (2004). Hereditary spastic paraplegia: Clinical genetic study of 15 families. Archives of Neurology, 61(6), 849–855.PubMedCrossRefGoogle Scholar
  5. 5.
    Schüle, R., & Schöls, L. (2011). Genetics of hereditary spastic paraplegias. Seminars in Neurology, 31(5), 484–493.PubMedCrossRefGoogle Scholar
  6. 6.
    Fink, J. K., & Hedera, P. (1999). Hereditary spastic paraplegia: Genetic heterogeneity and genotype-phenotype correlation. Seminars in Neurology, 19(3), 301–309.PubMedCrossRefGoogle Scholar
  7. 7.
    Ngudi, D. D., Kuo, Y. H., Van Montagu, M., & Lambein, F. (2012). Research on motor neuron diseases konzo and neurolathyrism: Trends from 1990 to 2010. PLoS Neglected Tropical Diseases, 6(7), e1759.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Kenwrick, S., Ionasescu, V., Ionasescu, G., Searby, C., King, A., Dubowitz, M., et al. (1986). Linkage studies of X-linked recessive spastic paraplegia using DNA probes. Human Genetics, 73(3), 264–266.PubMedCrossRefGoogle Scholar
  9. 9.
    Fonknechten, N., Mavel, D., Byrne, P., Davoine, C. S., Cruaud, C., Bönsch, D., et al. (2000). Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. Human Molecular Genetics, 9(4), 637–644.PubMedCrossRefGoogle Scholar
  10. 10.
    Sauter, S., Miterski, B., Klimpe, S., Bönsch, D., Schöls, L., Visbeck, A., et al. (2002). Mutation analysis of the spastin gene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia. Human Mutation, 20(2), 127–132.PubMedCrossRefGoogle Scholar
  11. 11.
    Depienne, C., Tallaksen, C., Lephay, J. Y., Bricka, B., Poea-Guyon, S., Fontaine, B., et al. (2006). Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases. Journal of Medical Genetics, 43(3), 259–265.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Alvarez, V., Sánchez-Ferrero, E., Beetz, C., Díaz, M., Alonso, B., Corao, A. I., et al. (2010). Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia. BMC Neurology, 10, 89.PubMedCentralPubMedGoogle Scholar
  13. 13.
    Magariello, A., Muglia, M., Patitucci, A., Ungaro, C., Mazzei, R., Gabriele, A. L., et al. (2010). Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia. Journal of Neurological Sciences, 288(1–2), 96–100.CrossRefGoogle Scholar
  14. 14.
    Dürr, A., Camuzat, A., Colin, E., Tallaksen, C., Hannequin, D., Coutinho, P., et al. (2004). Atlastin1 mutations are frequent in young-onset autosomal dominant spastic paraplegia. Archives of Neurology, 61(12), 1867–1872.PubMedCrossRefGoogle Scholar
  15. 15.
    Hehr, U., Bauer, P., Winner, B., Schule, R., Olmez, A., Koehler, W., et al. (2007). Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia. Annals of Neurology, 62(6), 656–665.PubMedCrossRefGoogle Scholar
  16. 16.
    Stevanin, G., Azzedine, H., Denora, P., Boukhris, A., Tazir, M., Lossos, A., et al. (2008). Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain, 131(Pt 3), 772–784.PubMedCrossRefGoogle Scholar
  17. 17.
    Goizet, C., Boukhris, A., Maltete, D., Guyant-Maréchal, L., Truchetto, J., Mundwiller, E., et al. (2009). SPG15 is the second most common cause of hereditary spastic paraplegia with thin corpus callosum. Neurology, 73(14), 1111–1119.PubMedCrossRefGoogle Scholar
  18. 18.
    Schüle, R., Brandt, E., Karle, K. N., Tsaousidou, M., Klebe, S., Klimpe, S., et al. (2009). Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia. Neurogenetics, 10(2), 97–104.PubMedCrossRefGoogle Scholar
  19. 19.
    Schüle, R., & Schöls, L. (2011). Genetics of hereditary spastic paraplegias. Seminars in Neurology, 31(5), 484–493.PubMedCrossRefGoogle Scholar
  20. 20.
    Goizet, C., Boukhris, A., Durr, A., Beetz, C., Truchetto, J., Tesson, C., et al. (2009). CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. Brain, 132(Pt 6), 1589–1600.PubMedCrossRefGoogle Scholar
  21. 21.
    Schlipf, N. A., Schüle, R., Klimpe, S., Karle, K. N., Synofzik, M., Schicks, J., et al. (2011). Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. Clinical Genetics, 80(2), 148–160.PubMedCrossRefGoogle Scholar
  22. 22.
    Arnoldi, A., Crimella, C., Tenderini, E., Martinuzzi, A., D’Angelo, M. G., Musumeci, O., et al. (2012). Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations. Clinical Genetics, 81(2), 150–157.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Neurogenetics BranchNINDS/NIHBethesdaUSA

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