Phenotypic Heterogeneity in Genetic and Acquired Pediatric Cerebellar Disorders
Granath, Katariina; Huhtaniska, Sanna; Ellonen, Juulia; Pokka, Tytti; Kangas, Salla M; Moilanen, Jukka; Helander, Heli; Kallankari, Hanna; Komulainen-Ebrahim, Jonna; Vieira, Päivi; Rahikkala, Elisa; Guerrini, Renzo; Honkila, Minna; Ruuska, Terhi S; Hinttala, Reetta; Suo-Palosaari, Maria; Tolonen, Jussi-Pekka; Uusimaa, Johanna (2025-05-06)
John Wiley & Sons
06.05.2025
Granath, K., Huhtaniska, S., Ellonen, J., Pokka, T., Kangas, S.M., Moilanen, J., Helander, H., Kallankari, H., Komulainen-Ebrahim, J., Vieira, P., Rahikkala, E., Guerrini, R., Honkila, M., Ruuska, T.S., Hinttala, R., Suo-Palosaari, M., Tolonen, J.-P. and Uusimaa, J. (2025), Phenotypic Heterogeneity in Genetic and Acquired Pediatric Cerebellar Disorders. Mov Disord. https://doi.org/10.1002/mds.30210
https://creativecommons.org/licenses/by/4.0/
© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202506305024
https://urn.fi/URN:NBN:fi:oulu-202506305024
Tiivistelmä
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 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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