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In this article, we present three unrelated individuals with novel compound heterozygous pathogenic <jats:italic>AARS2<\/jats:italic> variants underlying diverse clinical presentations. Patient 1 is a 51\u2010year\u2010old man with adult\u2010onset progressive cognitive, psychiatric, and motor decline and leukodystrophy. Patient 2 is a 34\u2010year\u2010old man with childhood\u2010onset progressive tremor followed by the development of polyneuropathy, ataxia, and mild cognitive and psychiatric decline without leukodystrophy on imaging. Patient 3 is a 57\u2010year\u2010old woman with childhood\u2010onset tremor and nystagmus which preceded dystonia, chorea, ataxia, depression, and cognitive decline marked by cerebellar atrophy and white matter disease. These cases expand the clinical heterogeneity of <jats:italic>AARS2\u2010<\/jats:italic>related disorders, given that the first and third case represent some of the oldest known survivors of this disease, the second is adult\u2010onset <jats:italic>AARS2<\/jats:italic>\u2010related neurological decline without leukodystrophy, and the third is biallelic <jats:italic>AARS2<\/jats:italic>\u2010related disorder involving a partial gene deletion.<\/jats:p>","DOI":"10.1002\/ajmg.a.61188","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T09:37:55Z","timestamp":1558085875000},"page":"1556-1564","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Expansion of the clinical spectrum associated with <i>AARS2<\/i>\u2010related disorders"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-1879","authenticated-orcid":false,"given":"Siddharth","family":"Srivastava","sequence":"first","affiliation":[{"name":"Department of Neurology Boston Children's Hospital  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankur","family":"Butala","sequence":"additional","affiliation":[{"name":"Department of Neurology The Johns Hopkins Hospital  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Mahida","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Jacksonville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-6755","authenticated-orcid":false,"given":"Weiyi","family":"Mu","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine The Johns Hopkins Hospital  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Poretti","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Hugo W. 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