CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients

Roux, Marie Le; Barth, Magalie; Guéden, Sophie; Cepoy, Patrick Desbordes de; Aeby, Alec; Vilain, Catheline; Hirsch, Édouard; Saint‐Martin, Anne de; Portes, Vincent Des; Lesca, Gaëtan; Riquet, Audrey; Chaton, Laurence; Villeneuve, Nathalie; Villard, Laurent; Cancés, Claude; Valton, Luc; Renaldo, Florence; Vermersch, Anne-Isabelle; Altuzarra, Cécilia; Nguyen-Morel, Marie-Ange; Gils, Julien Van; Angelini, C.; Biraben, Arnaud; Arnaud, Lionel; Riant, Florence; Bogaert, Patrick Van

doi:10.1016/j.ejpn.2021.05.010

Cited by 30 publications

(18 citation statements)

References 45 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Different phenotypical traits may overlap in a CACNA1A family: each family member can exhibit seizures, episodes of hemiplegia, migraine, or ataxic disorders with variable penetrance and expressivity. Some degree of intellectual disability can also occur [ 7 , 46 , 47 , 48 , 49 ]. With regard to epilepsy, two main alternative phenotypes have been identified in these patients (i) early and recurrent status epilepticus followed by drug-resistant focal-onset epilepsy, early progressive cerebellar signs, hemiplegic accesses with consciousness impairment, severe intellectual disability (ii) generalized epilepsy with early-onset refractory absence seizures, stable cerebellar dysfunction, and milder intellectual disability [ 7 ].…”

Section: Channelopathiesmentioning

confidence: 99%

Inherited Developmental and Epileptic Encephalopathies

Bartolini¹

2021

Neurology International

View full text Add to dashboard Cite

Epileptic encephalopathies often have a genetic etiology. The epileptic activity itself exerts a direct detrimental effect on neurodevelopment, which may add to the cognitive impairment induced by the underlying mutation (“developmental and epileptic encephalopathy”). The focus of this review is on inherited syndromes. The phenotypes of genetic disorders affecting ion channels, metabolic signalling, membrane trafficking and exocytosis, cell adhesion, cell growth and proliferation are discussed. Red flags suggesting family of genes or even specific genes are highlighted. The knowledge of the phenotypical spectrum can indeed prompt the clinician to suspect specific etiologies, expediting the diagnosis.

show abstract

Section: Channelopathiesmentioning

confidence: 99%

Inherited Developmental and Epileptic Encephalopathies

Bartolini¹

2021

Neurology International

View full text Add to dashboard Cite

show abstract

“…In general, seizures were correlated with GoF variants. A 2017 study of CACNA1A ‐associated epilepsy by Le Roux, et al 5 further identified two main seizure presentations, status epilepticus and intractable seizures or early onset absence seizures. The first, more severe phenotype, was associated with GoF variants while those with predominantly absence seizures were associated with LoF.…”

Section: Discussionmentioning

confidence: 99%

“…SCA6 is a late‐onset progressive cerebellar ataxia 3 . With increasing use of clinical exome/panel gene sequencing, pathogenic CACNA1A variants have been associated with a wider phenotypic spectrum including developmental delay/intellectual disability, epilepsy, developmental and epileptic encephalopathy 42 (DEE42; MIM 617106), paroxysmal dystonia, and neuropsychiatric disorders 1,4–6 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical and genetic characterization of CACNA1A‐related disease

Lipman¹,

Fan

Shen

et al. 2022

Clinical Genetics

View full text Add to dashboard Cite

Pathogenic variants in the CACNA1A gene have been associated with episodic ataxia type 2, familial hemiplegic migraine, and spinocerebellar ataxia 6. With increasing use of clinical genetic testing, associations have expanded to include developmental delay, epilepsy, paroxysmal dystonia, and neuropsychiatric disorders. We report 47 individuals with 33 unique likely pathogenic or pathogenic CACNA1A variants. A machine learning method, funNCion, was used to predict loss-of-function (LoF)/gain-offunction (GoF) impact of genetic variants, and a heuristic severity score was designed to analyze genotype/phenotype correlations. Commonly reported phenotypes include developmental delay/intellectual disability (96%), hemiplegic migraines (36%), episodic ataxia type 2 (32%), epilepsy (55%), autism spectrum disorder (23%), and paroxysmal tonic upward gaze (36%). Severity score was significantly higher for predicted GoF variants, variants in the S5/S6 helices, and the recurrent p.Val1392Met variant. Seizures/status epilepticus were correlated with GoF and were more frequent in those with the p.Val1392Met variant. Our findings demonstrate a breadth of disease severity in CACNA1A-related disease and suggest that the clinical phenotypic heterogeneity likely reflects diverse molecular phenotypes. A better understanding of the natural history of CACNA1A-related disease and genotype/phenotype correlations will help inform prognosis and prepare for future clinical trials.

show abstract

“…For instance, individuals with a clinical diagnosis of Dravet syndrome are likely to have a variant in a gene called SCN1A, and sodium-channel blockers should be avoided for treatment. Although several studies demonstrated that LEV showed effectiveness on epilepsy with genetic alteration (e.g., CACNA1 and STXBP1 mutation) [ 33 , 34 ], studies based on the efficacy of LEV as a treatment for epilepsy with genetic alterations are very scarce. Only a small number of children underwent genetic tests in this study; therefore, further extensive research efforts are required to identify the therapeutic effect of LEV associated with genetic abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy of Levetiracetam for Epilepsy in School-Aged Children with Intellectual Disability and Normal Intelligence

Moon

Han

2021

Brain Sciences

View full text Add to dashboard Cite

Choosing optimal anti-seizure medication (ASM) is very important in pediatric patients with epilepsy who attend school, especially children with an intellectual disability (ID). Levetiracetam (LEV) has proven to be an effective, safe, generally well-tolerated, broad-spectrum ASM in children. In the context of increasing use of LEV in school-aged children with epilepsy and ID, we evaluate relevant clinical data, including efficacy, safety, and tolerability in children with epilepsy and an intellectual disability (ID) or normal intelligence (NI). We performed a retrospective chart review of children and included 298 pediatric patients with epilepsy who were treated with LEV with NI (147) and ID (151). After 6 months, 96% of NI and 83% of ID subjects had a seizure reduction rate greater than 50% (p = 0.031). The tolerability of LEV was generally good, with 75% retention rates at 2 years in both groups and only minor side effects (under 15%). The retention rates of patients with NI and ID were 76% and 74%, respectively (p = 0.597). Thus, LEV showed considerable efficacy with minimal side effects and high retention rates and is an easily maintained and safe treatment option for pediatric epilepsy with ID. However, better-designed research studies are needed to clearly elucidate the efficacy and safety of LEV in children with epilepsy and ID.

show abstract

CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients

Cited by 30 publications

References 45 publications

Inherited Developmental and Epileptic Encephalopathies

Inherited Developmental and Epileptic Encephalopathies

Clinical and genetic characterization of CACNA1A‐related disease

Comparative Efficacy of Levetiracetam for Epilepsy in School-Aged Children with Intellectual Disability and Normal Intelligence

Contact Info

Product

Resources

About