Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry.
Détails
Etat: Public
Version: Final published version
Licence: CC BY-NC 4.0
ID Serval
serval:BIB_09EA9FB22258
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry.
Périodique
European heart journal
ISSN
1522-9645 (Electronic)
ISSN-L
0195-668X
Statut éditorial
Publié
Date de publication
14/09/2023
Peer-reviewed
Oui
Volume
44
Numéro
35
Pages
3357-3370
Langue
anglais
Notes
Publication types: Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Publication Status: 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.
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.
Mots-clé
Child, Humans, Calmodulin/genetics, Death, Sudden, Cardiac/etiology, Long QT Syndrome/diagnosis, Long QT Syndrome/genetics, Mutation/genetics, Registries, Tachycardia, Ventricular/diagnosis, Tachycardia, Ventricular/genetics, Calmodulin, Cardiomyopathies, Catecholaminergic polymorphic ventricular tachycardia, Idiopathic ventricular fibrillation, Long QT syndrome, Neurological disorders, Sudden death
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/08/2023 14:21
Dernière modification de la notice
09/08/2024 15:55