Diagnostic value of genetic testing, with focus on CACNA1A, in children with episodic neurologic disorders: a
Micaela Chinigioli1, Laura Martí-Sanchez2, Delia Yubero2
1Department of Pediatric Neurology, Fleni Institute, Buenos Aires, Argentina.
Insights
Genetic testing aids in diagnosing pediatric episodic neurologic disorders, especially when developmental delay or paroxysmal tonic upgaze is present. While the diagnostic yield is low, it supports integrating genetic analysis for broader genetic causes.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Episodic neurologic disorders in children pose diagnostic challenges.
- CACNA1A gene variants are linked to episodic ataxia and migraine, but diagnostic yield in pediatrics is unclear.
Purpose of the Study:
- To evaluate the diagnostic yield of genetic testing in pediatric patients with episodic neurologic disorders.
- To identify predictors of pathogenic variants in this population.
Main Methods:
- Retrospective study of 32 pediatric patients with episodic neurologic disorders.
- Clinical evaluation, neuroimaging, video EEG, and genetic testing were performed.
- Correlation of clinical and genetic data.
Main Results:
- Pathogenic variants identified in 6/32 patients, including 2 with CACNA1A variants.
- Genetic findings associated with developmental delay and paroxysmal tonic upgaze deviation.
- Variants found in genes beyond those classically linked to episodic disorders.
Conclusions:
- Genetic testing offers valuable insights for diagnosing pediatric episodic neurologic disorders.
- Integration of genetic testing is supported, especially for patients with developmental delay or specific symptoms.
- Broader genetic etiologies should be considered, and larger studies are needed.
Background:
Episodic neurologic disorders, such as paroxysmal torticollis, paroxysmal tonic upward gaze deviation, migraine, and episodic ataxia, represent a diagnostic challenge in paediatric patients. Variants in the CACNA1A and other genes such SCN8A and DEPDC5, have been implicated in episodic ataxia, hemiplegic migraine, and related conditions. However, the diagnostic yield of CACNA1A testing in paediatric populations with these symptoms remains uncertain.
Methods:
We conducted a retrospective study at Hospital Sant Joan de Déu, Barcelona, analysing 32 paediatric patients with episodic neurologic disorders. Clinical evaluation, neuroimaging, video EEG, and genetic testing were performed. Clinical and genetic data were correlated to identify predictors of pathogenic variants.
Results:
The cohort included 32 patients (21 females), with a mean age at symptom onset of 1.3 years. Paroxysmal torticollis (12/32) and paroxysmal tonic upgaze deviation (9/32) were the most frequent initial symptoms. Pathogenic variants were identified in 6/32 patients, of whom 2 carried CACNA1A variants. Positive genetic findings were significantly associated with developmental delay (p = 0.0056) and paroxysmal tonic upgaze deviation (p = 0.0185). Additional variants were identified in genes not classically linked to episodic disorders, including KAT6A, NFIX, and DEPDC5. Neuroimaging abnormalities were observed in 7/22 patients, and EEG abnormalities in 3/16.
Conclusions:
Genetic testing provides important insights in the evaluation of paediatric patients with episodic neurologic disorders, particularly in those with developmental delay, paroxysmal tonic upgaze, or episodic ataxia. Although the overall diagnostic yield remained low, consistent with other paroxysmal movement disorders, these findings support the integration of genetic testing into the diagnostic algorithm and underscore the need to consider broader genetic aetiologies. Larger studies are warranted to confirm these observations.
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