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This classification system still largely frames clinical thinking and genetic workup in clinical practice. Yet, with the advent of next\u2010generation sequencing, phenotypically unbiased studies have revealed the limitations of this classification system. Various genes (eg, <jats:italic>SPG7, SYNE1, PNPLA6<\/jats:italic>) traditionally rooted in either the ataxia or hereditary spastic paraplegia classification system have now been shown to cause ataxia on the one end of the disease continuum and hereditary spastic paraplegia on the other. Other genes such as <jats:italic>GBA2<\/jats:italic> and <jats:italic>KIF1C<\/jats:italic> were almost simultaneously published as both a hereditary spastic paraplegia and an ataxia gene. The variability and fluidity of observed phenotypes along the ataxia\u2010spasticity spectrum warrants a rethinking of the traditional classification system. We propose to replace this divisive diagnosis\u2010driven ataxia and hereditary spastic paraplegia classification system by a descriptive, unbiased approach of <jats:italic>modular phenotyping<\/jats:italic>. This approach is also open to expansion of the phenotype beyond ataxia and spasticity, which often occur as part of broader multisystem neuronal dysfunction. The concept of a continuous ataxia\u2010spasticity disease spectrum is further supported by ataxias and hereditary spastic paraplegias sharing not only overlapping phenotypes and underlying genes, but also common cellular pathways and disease mechanisms. This suggests a shared vulnerability of cerebellar and corticospinal neurons for common pathophysiological processes. It might be this <jats:italic>mechanistic<\/jats:italic> overlap that drives their <jats:italic>clinical<\/jats:italic> overlap. A mechanistically inspired classification system will help to pave the way for mechanism\u2010based strategies for drug development. \u00a9 2017 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26944","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T06:35:23Z","timestamp":1487054123000},"page":"332-345","source":"Crossref","is-referenced-by-count":188,"title":["Overcoming the divide between ataxias and spastic paraplegias: Shared phenotypes, genes, and pathways"],"prefix":"10.1002","volume":"32","author":[{"given":"Matthis","family":"Synofzik","sequence":"first","affiliation":[{"name":"Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH) University of T\u00fcbingen T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sch\u00fcle","sequence":"additional","affiliation":[{"name":"Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH) University of T\u00fcbingen T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,14]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Man OMIi.Online Mendelian Inheritance in Man OMIM. 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