Long-term clinical observation of patients with heterozygous KIF1A variants.
KIF1A
cerebellar atrophy
optic radiation
peripheral neuropathy
spastic paraplegia
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
17 May 2024
17 May 2024
Historique:
received:
10
03
2024
accepted:
27
04
2024
medline:
18
5
2024
pubmed:
18
5
2024
entrez:
17
5
2024
Statut:
aheadofprint
Résumé
KIF1A-related disorders (KRDs) encompass recessive and dominant variants with wide clinical variability. Recent genetic investigations have expanded the clinical phenotypes of heterozygous KIF1A variants. However, there have been a few long-term observational studies of patients with heterozygous KIF1A 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 KIF1A variants. To understand the long-term 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-up period was 30 years (4-44 years). This long-term 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-related 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-related progression of cerebellar atrophy and the appearance of hyperintensity of optic radiation on T2WI and FLAIR imaging. Long-term follow-up 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-genotype correlation.
Identifiants
pubmed: 38760879
doi: 10.1002/ajmg.a.63656
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e63656Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23ek0109674
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23ek0109549
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23ek0109617
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23ek0109648
Organisme : Japanese Society for the Promotion of Science KAKENHI
ID : JP23H02877
Organisme : Takeda Science Foundation
Organisme : Astellas Pharma
Informations de copyright
© 2024 Wiley Periodicals LLC.
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