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Updated: May 9, 2025
Cerebellar Regional Dissection for Molecular Analysis
Published on: December 5, 2020
Phenotypic Heterogeneity in Genetic and Acquired Pediatric Cerebellar Disorders
Katariina Granath1,2, Sanna Huhtaniska3, Juulia Ellonen1,2
1Department of Paediatrics and Adolescent Medicine, Division of Paediatric Neurology, Oulu University Hospital, Oulu, Finland.
Insights
Pediatric cerebellar disorders (PCDs) in Finland are genetically diverse, with ataxia being common. Next-generation sequencing aids in diagnosing these rare genetic conditions.
Area of Science:
- Neurology
- Genetics
- Epidemiology
Background:
- The genetic basis of pediatric cerebellar disorders (PCDs) in Finland remains largely uncharacterized.
- Understanding the genetic landscape is crucial for diagnosis and treatment.
Purpose of the Study:
- To define the epidemiological, clinical, neuroradiological, and genetic features of PCDs in Northern Finland.
- To establish genotype-phenotype correlations in a well-defined cohort.
Main Methods:
- A longitudinal, population-based cohort study of children diagnosed with movement disorders or cerebellar malformations (≤16 years) from 1970-2022.
- Comparison of genotype-phenotype data with 1007 published cases of monogenic cerebellar disorders.
Main Results:
- Identified 107 patients with a cumulative incidence of 21.9 per 100,000 live births.
- Determined etiology in 59 patients: 66% monogenic, 12% chromosomal, 22% non-genetic. Ataxia was the most frequent presentation.
- Next-generation sequencing (NGS) achieved a 65% diagnostic yield for ataxia, with common features including ataxia, developmental delay, and seizures.
Conclusions:
- Pediatric cerebellar disorders are a heterogeneous group with a significant genetic component.
- Clinical presentation and age of onset can aid in differentiating specific PCD entities.
- This dataset supports clinical recognition of PCDs and their genetic causes, highlighting the need for further research into treatment development.
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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