Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry.
Calmodulin
Cardiomyopathies
Catecholaminergic polymorphic ventricular tachycardia
Idiopathic ventricular fibrillation
Long QT syndrome
Neurological disorders
Sudden death
Journal
European heart journal
ISSN: 1522-9645
Titre abrégé: Eur Heart J
Pays: England
ID NLM: 8006263
Informations de publication
Date de publication:
14 09 2023
14 09 2023
Historique:
received:
18
01
2023
revised:
14
04
2023
accepted:
13
06
2023
medline:
15
9
2023
pubmed:
2
8
2023
entrez:
2
8
2023
Statut:
ppublish
Résumé
Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator.
Identifiants
pubmed: 37528649
pii: 7235120
doi: 10.1093/eurheartj/ehad418
pmc: PMC10499544
doi:
Substances chimiques
Calmodulin
0
Types de publication
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3357-3370Subventions
Organisme : Medical Research Council
ID : MR/T024062/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : K23 HL130554
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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