Phenotypic Heterogeneity in Genetic and Acquired Pediatric Cerebellar Disorders
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Movement Disorders
DOI: 10.1002/mds.30210
Authors: Katariina Granath, Sanna Huhtaniska, Juulia Ellonen, Tytti Pokka, Salla M. Kangas, Jukka Moilanen, Heli Helander, Hanna Kallankari, Jonna Komulainen‐Ebrahim, Päivi Vieira, Elisa Rahikkala, Renzo Guerrini, Minna Honkila, Terhi S. Ruuska, Reetta Hinttala, Maria Suo‐Palosaari, Jussi‐Pekka Tolonen, Johanna Uusimaa
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
Funders: Suomen Lääketieteen Säätiö, Medical Research Center Oulu, University of Oxford, European Commission, Academy of Finland, Ministero della Salute, Jane ja Aatos Erkon Säätiö, Lastentautien Tutkimussäätiö, Oulun Yliopisto, Sigrid Juséliuksen Säätiö, Orionin Tutkimussäätiö, Stiftelsen Alma och K. A. Snellman Säätiö, Regione Toscana, Fondazione Cassa di Risparmio di Firenze, H2020 Marie Skłodowska-Curie Actions
Awards: Childhood-onset genetic brain white matter diseases – novel diseases as tools to study myelin formation, maintenance and demyelination, G3217225776, Congenital heart disease-associated arrhythmia:
deciphering Hamamy syndrome, novel rare disease, using iPS cells, Using patient-derived human induced pluripotent stem cells (hiPSCs) to interrogate disease mechanisms and treatment in spinocerebellar ataxias, Childhood-Onset Diseases of the Cerebellum: Epidemiology, Novel Disorders, and Disease Modelling Using Cerebellar Organoids, Using patient-derived human induced pluripotent stem cells (hiPSCs) to interrogate disease mechanisms and treatment in spinocerebellar ataxias
OpenAlex ID: W4410136560