Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 6.
doi: 10.1002/mds.30210. Online ahead of print.

Phenotypic Heterogeneity in Genetic and Acquired Pediatric Cerebellar Disorders

Katariina Granath  1   2 , Sanna Huhtaniska  3 , Juulia Ellonen  1   2 , Tytti Pokka  2   4 , Salla M Kangas  2 , Jukka Moilanen  2   5 , Heli Helander  1   2 , Hanna Kallankari  1   2 , Jonna Komulainen-Ebrahim  1   2 , Päivi Vieira  1   2 , Elisa Rahikkala  2   5 , Renzo Guerrini  6 , Minna Honkila  2   7 , Terhi S Ruuska  2   7   8 , Reetta Hinttala  2   8 , Maria Suo-Palosaari  3 , Jussi-Pekka Tolonen  1   2 , Johanna Uusimaa  1   2
Affiliations

Phenotypic Heterogeneity in Genetic and Acquired Pediatric Cerebellar Disorders

Katariina Granath et al. Mov Disord. .

Abstract

Background: The genetic landscape of pediatric cerebellar disorders (PCDs) in Finland is undefined.

Objectives: The objective was to define epidemiological, clinical, neuroradiological, and genetic characteristics of PCDs in Northern Finland.

Methods: A longitudinal population-based cohort study of children with a movement disorder or a cerebellar malformation (diagnosis ≤16 years; study period 1970-2022) was performed in the tertiary catchment area of the Oulu University Hospital, Finland. The genotype-to-phenotype associations were compared with 1007 published cases with matching monogenic etiologies.

Results: A total of 107 patients were included (cumulative incidence 21.9 per 100,000 live births). A defined genetic or non-genetic etiology was identified for 59 patients. These etiologies were monogenic (66%), chromosomal (12%), or non-genetic (22%). Ataxia was the most common movement disorder. Friedreich's ataxia was uncommon, whereas ataxias belonging to the Finnish Disease Heritage were overrepresented. Forty-eight cases remained undefined. The diagnostic yield (ie, pathogenic or likely pathogenic variants) of next-generation sequencing (NGS) in ataxia was 65%. Common features were ataxia, developmental delay, seizures, hypotonia, and abnormality in brain MRI, whereas hearing loss, sensory neuropathy, and microcephalia were associated with fewer etiologies.

Conclusions: PCDs are a heterogeneous disease group with a high proportion of genetic etiologies. Age of onset and certain clinical findings may help distinguish between different disease entities. The diagnostic yield of NGS has increased over time. Our dataset will support clinicians to recognize PCDs, their co-morbidities, and genetic etiologies. Further data on epidemiology, shared disease mechanisms, and the natural history of PCDs will be critical for the development of treatment approaches. © 2025 International Parkinson and Movement Disorder Society.

Keywords: ataxia; cerebellum; neurogenetics; neuroimaging; pediatric.

PubMed Disclaimer

References

    1. O'malley JA. Diagnosing common movement disorders in children. Continuum (Minneap Minn) 2022;28(5):1476–1519. https://doi.org/10.1212/CON.0000000000001187
    1. Kurian MA, Dale RC. Movement disorders presenting in childhood. Continuum (Minneap Minn) 2016;22(4):1159–1185. https://doi.org/10.1212/CON.0000000000000367
    1. Serrallach BL, Orman G, Boltshauser E, Hackenberg A, Desai NK, Kralik SF, et al. Neuroimaging in cerebellar ataxia in childhood: a review. J Neuroimaging 2022 Sep 1;32(5):825–851.
    1. Musselman KE, Stoyanov CT, Marasigan R, et al. Prevalence of ataxia in children: a systematic review. Neurology 2014;82(1):80–89. https://doi.org/10.1212/01.wnl.0000438224.25600.6c
    1. Traschütz A, Adarmes‐Gomez A, Anheim M, Baets J, Falkenburger B, Gburek‐Augustat J, et al. Autosomal recessive cerebellar ataxias in Europe: frequency, onset, and severity in 677 patients. Mov Disord 2023;38(6):1109–1112. https://doi.org/10.1002/mds.29397