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Genetics of Hereditary Spastic Paraplegias (HSP)

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Movement Disorder Genetics

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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 identified 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 HSP-like 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 field, we propose an algorithm for a time- and cost-efficient strategy for genetic diagnostics in HSP.

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Authors and Affiliations

  1. Department of Neurodegenerative Disease – Movement Disorder Genomics, University of Tübingen Center for Neurology, Tübingen, 72076, Germany

    Rebecca Schüle MD

  2. Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, 72076, Germany

    Ludger Schöls MD

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  1. Department of Neurology, University Hospital Kiel, Kiel, Germany

    Susanne A. Schneider

  2. Department of Molecular Neuroscience, University College London, Institute of Neurology, London, United Kingdom

    José M. Tomás Brás

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Schüle, R., Schöls, L. (2015). Genetics of Hereditary Spastic Paraplegias (HSP). In: Schneider, S., Brás, J. (eds) Movement Disorder Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-17223-1_16

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