Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry

被引：32

作者：

Crotti, Lia ^{[1
,2
,3
]}

Spazzolini, Carla ^{[1
,2
]}

Nyegaard, Mette ^{[4
]}

Overgaard, Michael T. ^{[5
]}

Kotta, Maria-Christina ^{[1
,2
]}

Dagradi, Federica ^{[1
,2
]}

Sala, Luca ^{[1
,2
,6
]}

Aiba, Takeshi ^{[7
]}

Ayers, Mark D. ^{[8
]}

Baban, Anwar ^{[9
,10
]}

Barc, Julien ^{[11
]}

Beach, Cheyenne M. ^{[12
]}

Behr, Elijah R. ^{[13
,14
]}

Bos, J. Martijn ^{[15
,16
,17
]}

Cerrone, Marina ^{[18
]}

Covi, Peter ^{[19
]}

Cuneo, Bettina ^{[20
]}

Denjoy, Isabelle ^{[21
]}

Donner, Birgit ^{[22
]}

Elbert, Adrienne ^{[23
]}

Eliasson, Hakan ^{[24
,25
]}

Etheridge, Susan P. ^{[26
,27
]}

Fukuyama, Megumi ^{[28
]}

Girolami, Francesca ^{[29
]}

Hamilton, Robert ^{[30
]}

Horie, Minoru ^{[28
]}

Iascone, Maria ^{[31
]}

Jaimez, Juan Jimenez ^{[32
]}

Jensen, Henrik Kjaerulf ^{[33
]}

Kannankeril, Prince J. ^{[34
]}

Kaski, Juan P. ^{[35
,36
]}

Makita, Naomasa ^{[37
,38
]}

Munoz-Esparza, Carmen ^{[9
,39
]}

Odland, Hans H. ^{[40
]}

Ohno, Seiko ^{[41
]}

Papagiannis, John ^{[42
]}

Porretta, Alessandra Pia ^{[43
]}

Prandstetter, Christopher ^{[44
,45
]}

Probst, Vincent ^{[46
]}

Robyns, Tomas ^{[9
,47
]}

Rosenthal, Eric ^{[48
]}

Roses-Noguer, Ferran ^{[9
,49
,50
]}

Sekarski, Nicole ^{[51
]}

Singh, Anoop ^{[52
]}

Spentzou, Georgia ^{[53
]}

Stute, Fridrike ^{[54
]}

Tfelt-Hansen, Jacob ^{[9
,55
,56
]}

Till, Jan ^{[50
]}

Tobert, Kathryn E.

Vinocur, Jeffrey M. ^{[12
]}

机构：

[1] Ist Auxol Italiano IRCCS, Ctr Cardiac Arrhythmias Genet Origin, Via Pier Lombardo 22, I-20135 Milan, Italy

[2] Ist Auxol Italiano IRCCS, Lab Cardiovasc Genet, Via Pier Lombardo 22, I-20135 Milan, Italy

[3] Univ Milano Bicocca, Dept Med & Surg, Piazza Ateneo Nuovo 1, I-20126 Milan, Italy

[4] Aalborg Univ, Dept Hlth Sci & Technol, Aalborg, Denmark

[5] Aalborg Univ, Dept Chem & Biosci, Aalborg, Denmark

[6] Univ Milano Bicocca, Dept Biotechnol & Biosci, Milan, Italy

[7] Natl Cerebral & Cardiovasc Ctr, Div Arrhythmia, Suita, Japan

[8] Indiana Univ Sch Med, Dept Pediat, Div Pediat Cardiol, Indianapolis, IN USA

[9] European Reference Network Rare & Low Prevalence C, Rome, Italy

[10] Bambino Gesu Pediat Hosp, IRCCS, Pediat Cardiol & Arrhythmia Syncope Units, Rome, Italy

[11] Univ Nantes, Inst Thorax, CHU Nantes, CNRS,INSERM, Nantes, France

[12] Yale Sch Med, Pediat Cardiol, New Haven, CT USA

[13] St Georges Univ London, Inst Mol & Clin Sci, Cardiol Sect, London, England

[14] St Georges Univ Hosp NHS Fdn Trust, Cardiovasc Clin Acad Grp, London, England

[15] Mayo Clin, Dept Cardiovasc Med, Div Heart Rhythm Serv & Pediat Cardiol, Windland Smith Rice Sudden Death Genom Lab, 200 First St SW, Rochester, MN 55905 USA

[16] Mayo Clin, Dept Pediat & Adolescent Med, Div Heart Rhythm Serv & Pediat Cardiol, Windland Smith Rice Sudden Death Genom Lab, 200 First St SW, Rochester, MN 55905 USA

[17] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Div Heart Rhythm Serv & Pediat Cardiol, Windland Smith Rice Sudden Death Genom Lab, 200 First St SW, Rochester, MN 55905 USA

[18] NYU, Leon H Charney Div Cardiol, Inherited Arrhythmias Clin, Grossmann Sch Med, New York, NY USA

[19] Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria

[20] Univ Denver, Dept Pediat, Sect Cardiol, Sch Med, Aurora, CO USA

[21] Grp Hosp Bichat Claude Bernard, Ctr Reference Malad Cardiaques Hereditaires Filier, Dept Rythmol, Paris, France

[22] Univ Kinderspital Beider Basel UKBB, Kardiol, Basel, Switzerland

[23] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[24] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden

[25] Karolinska Univ Hosp, Pediat Cardiol C8 34, Stockholm, Sweden

[26] Univ Utah, Dept Pediat, Div Pediat Cardiol, Salt Lake City, UT USA

[27] Primary Childrens Med Ctr, Salt Lake City, UT USA

[28] Shiga Univ Med Sci, Dept Cardiovasc Med, Shiga, Japan

[29] Meyer Childrens Hosp, Cardiol Unit, Florence, Italy

[30] Hosp Sick Children SickKids, Div Cardiol, Toronto, ON, Canada

[31] ASST Papa Giovanni XXIII, Lab Genet Med, Bergamo, Italy

[32] Hosp Univ Virgen de las Nieves, Inst Invest Biosanitario IBS Granada, Granada, Spain

[33] Aarhus Univ, Aarhus Univ Hosp, Dept Cardiol, Dept Clin Med, DK-8200 Aarhus, Denmark

[34] Vanderbilt Univ, Dept Pediat, Med Ctr, Nashville, TN USA

[35] UCL, Inst Cardiovasc Sci, Ctr Paediat Inherited & Rare Cardiovasc Dis, Zayed Ctr Res Rare Dis Childhood, London, England

[36] Great Ormond St Hosp Sick Children, Ctr Inherited Cardiovasc Dis, London, England

[37] Natl Cerebral & Cardiovasc Ctr, Suita, Japan

[38] Sapporo Teishinkai Hosp, Sapporo, Japan

[39] Hosp Univ Virgen Arrixaca, Inherited Cardiac Dis Unit, Murcia, Spain

[40] Oslo Univ Hosp, Dept Cardiol & Pediat Cardiol, Sect Arrhythmias, Oslo, Norway

[41] Natl Cerebral & Cardiovasc Ctr, Dept Biosci & Genet, Osaka, Japan

[42] Onassis Cardiac Surg Ctr, Pediat & Adult Congenital Heart Dis, Athens, Greece

[43] CHU Vaudois, Serv Cardiol, Unite Troubles Rythme, Lausanne, Switzerland

[44] Johannes Kepler Univ Linz, Med Fac, Linz, Austria

[45] Kepler Univ Hosp, Dept Pediat Cardiol, Linz, Austria

[46] CHU Nantes, Inst Thorax, Serv Cardiol, Nantes, France

[47] Univ Hosp Leuven, Dept Cardiovasc Dis, Leuven, Belgium

[48] St Thomas Hosp, Evelina London Childrens Hosp, London, England

[49] Vall dHebron Univ Hosp, Paediat Cardiol Dept, Barcelona, Spain

[50] Royal Brompton Hosp NHS Guys & St Thomas Fdn Trust, London, England

来源：

EUROPEAN HEART JOURNAL | 2023年 / 44卷 / 35期

关键词：

Calmodulin; Long QT syndrome; Catecholaminergic polymorphic ventricular tachycardia; Idiopathic ventricular fibrillation; Sudden death; Cardiomyopathies; Neurological disorders; LONG-QT SYNDROME; CALCIUM-CHANNEL; HYPERTROPHIC CARDIOMYOPATHY; ARRHYTHMIA;

D O I：

10.1093/eurheartj/ehad418

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims 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. Methods and results 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. Conclusion 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.

引用

页码：3357 / 3370

页数：14

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