An asymptomatic 14 years of age female had a cardiac arrest while rushing up the stairs and was revived with three AED shocks. Her electrocardiogram showed left ventricular hypertrophy and a prolonged QT interval (527 ms). Imaging revealed thickened heart muscles and excessive trabeculations. She recovered and received an implantable defibrillator, along with medication treatment. An exercise examination showed no irregular heartbeats. She is one of 12 siblings, all healthy, with a family history of sudden cardiac death in a paternal aunt.
Genetic testing using cardiac exome-focused panel revealed a heterozygous NM_001743.6(CALM2):c.400G>A (p.(Asp134Asn)) missense change, while the other genes in the panel were normal. Her parents declined further genetic screening. Calmodulin genetic changes, identified in the CALM 1-3 genes, are known to cause long QT syndrome.
Figure. “Patient cardiac phenotype. A, Two initiations of ventricular fibrillation (VF) recorded with the automatic external defibrillator during cardiopulmonary resuscitation. A pause is seen before each VF episode. The arrows indicate the onset of VF following a short-coupled premature ventricular complex. B, Baseline ECG showing sinus rhythm, prolonged QT interval (QTc=527 ms), and left ventricular (LV) hypertrophy. C, Echocardiographic apical 4-chamber view with marked septal and apical LV hypertrophy and LV excessive trabeculation. D, Cardiac magnetic resonance imaging showing septal hypertrophy and LV excessive trabeculation areas at the LV apex and the lateral free wall (red arrows). aVF indicates augmented vector foot; aVL, augmented vector left; and aVR, augmented vector right.”
A Unique Case of CALM2-Associated Long QT Syndrome
This individual is the first reported instance of calmodulinopathy related to long QT syndrome, hypertrophic cardiomyopathy, and increased trabeculation in a 12 years of age female who experienced ventricular fibrillation. It underscores the diverse phenotypic manifestations of CALM genetic changes and the crucial role of calmodulin in cardiac signaling mechanisms.
regarding secondary findings: Including CALM1, CALM2, and CALM3
A First Report of Calmodulinopathy with Long QT Syndrome
Long QT syndrome (LQTS) is a serious heart rhythm disorder that affects many individuals and their families. It’s characterized by a prolonged recovery phase of the heart following a heartbeat, which can lead to fainting, seizures, or even sudden cardiac arrest. This can be extremely frightening for those affected. Long QT syndrome can be inherited or acquired, and it requires careful management.
In some cases, individuals may have a rare subtype of Long QT syndrome called calmodulinopathy, which can lead to severe symptoms and complications, causing a great deal of worry and anxiety. The management of Long QT syndrome involves lifestyle changes, medications, and possibly surgical procedures, which can understandably be overwhelming and distressing for patients and their loved ones.
It’s crucial to provide early diagnosis and appropriate treatment to prevent sudden cardiac death and provide peace of mind for those affected. Genetic counseling and testing are important for identifying carriers and managing the risk effectively, offering a sense of control and understanding for the whole family.
