Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry
Calmodulinopathy is a condition caused by mutations in three genes (CALM 1-3) encoding for the same calmodulin protein, that can lead to dangerous heart rhythm problems, especially in young people. The International Calmodulinopathy Registry (ICalmR), established within ERN-GUARD Heart, is trying to understand this condition better by gathering clinical and genetic information from patients followed all over the world.
So far, ICalmR has enrolled 140 patients, most of whom are children or young adults. The most common forms of Calmodulinopathy are associated with serious ventricular arrhythmias and risk of sudden cardiac death and the most common clinical presentation are those of the Long QT Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia. Surprisingly, some patients showed neurological problems not secondary to a cardiac arrest and some patients also have heart structural abnormalities, which can lead to heart failure and even death.
While Calmodulinopathy can still be considered a very serious condition, the most recent data, presented in this article, show a trend in terms of reduction of severe arrhythmic events and sudden cardiac death compared to earlier data. Additionally, there is an increase in cases where multiple family members are affected, sometimes with different symptoms. However, there are still challenges in deciding the best treatment, as the data collected so far do not allow definitive recommendations.
Conclusion: Calmodulinopathy can have various presentations, ranging from heart rhythm problems to more complex syndromes. The severity of symptoms varies widely, and more cases of milder forms of the condition are being identified. Treatment typically involves medications and sometimes surgery to manage symptoms, but there is no one-size-fits-all approach yet. Many patients also require implantable devices like defibrillators to help preventing the risk of a sudden cardiac death.
Article: Crotti L, Spazzolini C, Nyegaard M, Overgaard MT, Kotta MC, Dagradi F, Sala L, Aiba T, Ayers MD, Baban A, Barc J, Beach CM, Behr ER, Bos JM, Cerrone M, Covi P, Cuneo B, Denjoy I, Donner B, Elbert A, Eliasson H, Etheridge SP, Fukuyama M, Girolami F, Hamilton R, Horie M, Iascone M, Jaimez JJ, Jensen HK, Kannankeril PJ, Kaski JP, Makita N, Muñoz-Esparza C, Odland HH, Ohno S, Papagiannis J, Porretta AP, Prandstetter C, Probst V, Robyns T, Rosenthal E, Rosés-Noguer F, Sekarski N, Singh A, Spentzou G, Stute F, Tfelt-Hansen J, Till J, Tobert KE, Vinocur JM, Webster G, Wilde AAM, Wolf CM, Ackerman MJ, Schwartz PJ. Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry.
Eur Heart J 2023;44:3357-3370. PMID: 37528649
Abstract prepared by Lia Crotti (Istituto Auxologico Italiano, Milano, Italy) and Carmen Balan (CardioGen Patients Association, Romania)