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Recent genetic investigations have expanded the clinical phenotypes of heterozygous <jats:italic>KIF1A<\/jats:italic> variants. However, there have been a few long\u2010term observational studies of patients with heterozygous <jats:italic>KIF1A<\/jats:italic> variants. A retrospective chart review of consecutive patients diagnosed with spastic paraplegia at Miyagi Children's Hospital from 2016 to 2020 identified six patients with heterozygous <jats:italic>KIF1A<\/jats:italic> variants. To understand the long\u2010term changes in clinical symptoms, we examined these patients in terms of their characteristics, clinical symptoms, results of electrophysiological and neuroimaging studies, and genetic testing. The median follow\u2010up period was 30\u2009years (4\u201344\u2009years). This long\u2010term observational study showed that early developmental delay and equinus gait, or unsteady gait, are the first signs of disease onset, appearing with the commencement of independent walking. In addition, later age\u2010related progression was observed in spastic paraplegia, and the appearance of axonal neuropathy and reduced visual acuity were characteristic features of the late disease phenotype. Brain imaging showed age\u2010related progression of cerebellar atrophy and the appearance of hyperintensity of optic radiation on T2WI and FLAIR imaging. Long\u2010term follow\u2010up revealed a pattern of steady progression and a variety of clinical symptoms, including spastic paraplegia, peripheral neuropathy, reduced visual acuity, and some degree of cerebellar ataxia. Clinical variability between patients was observed to some extent, and therefore, further studies are required to determine the phenotype\u2013genotype correlation.<\/jats:p>","DOI":"10.1002\/ajmg.a.63656","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T03:45:16Z","timestamp":1716003916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Long\u2010term clinical observation of patients with heterozygous <scp><i>KIF1A<\/i><\/scp> variants"],"prefix":"10.1002","volume":"194","author":[{"given":"Aritomo","family":"Kawashima","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology Miyagi Children's Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Kodama","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Miyagi Children's Hospital  Sendai 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