Clinical phenotypes of infantile onset CACNA1A-related disorder
Tamar Gur-Hartman1, Oren Berkowitz2, Keren Yosovich3
1Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel; Pediatric Movement Disorders Service, Wolfson Medical Center, Holon, Israel; School of Psychological Sciences, Tel-Aviv University, Israel.
Insights
Infantile onset CACNA1A-related disorders frequently involve cerebellar ataxia and paroxysmal non-epileptic events. Cognitive difficulties are common, and epilepsy risk increases after age two, especially with congenital cerebellar ataxia.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- CACNA1A-related disorders encompass cerebellar ataxia and paroxysmal events like seizures.
- Phenotypes often overlap and co-exist in affected individuals.
Purpose of the Study:
- To characterize phenotypes in infantile-onset CACNA1A-related disorder.
- To investigate intra-familial variations and genotype-phenotype correlations.
Main Methods:
- Multicenter international collaboration.
- Retrospective chart review of 47 patients with infantile-onset CACNA1A disorder.
- Analysis of clinical, radiological, and genetic data.
Main Results:
- Congenital cerebellar ataxia (CCA) affected 51% of infants; paroxysmal non-epileptic events (PNEE) occurred in 68%.
- Cognitive difficulties were present in 70% of children, associated with CCA.
- Epilepsy developed in some children after age two, with febrile convulsions and CCA indicating higher risk.
Conclusions:
- Infants commonly present with CCA, PNEE, or both.
- Cognitive impairment is frequent and linked to CCA.
- Epilepsy onset is more common after age two; early febrile convulsions with CCA may predict later epilepsy.
Background:
CACNA1A-related disorders present with persistent progressive and non-progressive cerebellar ataxia and paroxysmal events: epileptic seizures and non-epileptic attacks. These phenotypes overlap and co-exist in the majority of patients.
Objective:
To describe phenotypes in infantile onset CACNA1A-related disorder and to explore intra-familial variations and genotype-phenotype correlations.
Material And Methods:
This study was a multicenter international collaboration. A retrospective chart review of CACNA1A patients was performed. Clinical, radiological, and genetic data were collected and analyzed in 47 patients with infantile-onset disorder.
Results:
Paroxysmal non-epileptic events (PNEE) were observed in 68% of infants, with paroxysmal tonic upward gaze (PTU) noticed in 47% of infants. Congenital cerebellar ataxia (CCA) was diagnosed in 51% of patients including four patients with developmental delay and only one neurological sign. PNEEs were found in 63% of patients at follow-up, with episodic ataxia (EA) in 40% of the sample. Cerebellar ataxia was found in 58% of the patients at follow-up. Four patients had epilepsy in infancy and nine in childhood. Seven infants had febrile convulsions, three of which developed epilepsy later; all three patients had CCA. Cognitive difficulties were demonstrated in 70% of the children. Cerebellar atrophy was found in only one infant but was depicted in 64% of MRIs after age two.
Conclusions:
Nearly all of the infants had CCA, PNEE or both. Cognitive difficulties were frequent and appeared to be associated with CCA. Epilepsy was more frequent after age two. Febrile convulsions in association with CCA may indicate risk of epilepsy in later childhood. Brain MRI was normal in infancy. There were no genotype-phenotype correlations found.
More Related Videos
07:38Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane
Published on: March 30, 2015
05:32High-speed Video Microscopy Analysis for First-line Diagnosis of Primary Ciliary Dyskinesia
Published on: January 19, 2022
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:19Autism Spectrum Disorder
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
01:20Inborn Errors of Metabolism
01:28Conduct Disorder
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:30Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....