Hypertrophic cardiomyopathy and long QT syndrome in cardiac-only Timothy syndrome

Figure 1. Patient pedigree. Patient is depicted by arrow. ⌀ = not present; a/w = alive and well; br. ca = breast cancer; chol = hypercholesterolemia; CM = cardiomyopathy; CV = cardiovascular disease; dx. = diagnosed; EKG = electrocardiogram; HCM = hypertrophic cardiomyopathy; H/O EtOH = history of alcohol use disorder; ov. ca = ovarian cancer; SCD = sudden cardiac death.

Figure 2. Clinical cardiac testing. A: An electrocardiogram showing sinus bradycardia with a QT interval of 562–590 ms that was manually corrected to 480–490 ms. B: Echocardiographic apical 4-chamber view in end-systole (left) and end-diastole (right) demonstrating markedly hypertrophied septum. C: Magnetic resonance perfusion imaging (without contrast) in end-systole (left) and end-diastole (right) demonstrating septal hypertrophy.

Figure 3. Overview of cardiac L-type calcium channel protein. A: Schematic representation of the channel protein with domains embedded in the membrane and location of known pathogenic variants. Red symbols are mutations associated with Timothy syndrome (TS), green symbols show variants associated with isolated QT prolongation, and yellow symbols are variants associated with incomplete TS phenotype. B: Side view and C: intracellular view of a proposed protein structure of the Cav1.2 protein based on structure of Cav1.1. The R518 residue is highlighted in yellow. Proposed structure generated with AlphaFold.12

Supplemental Figure 1. Additional ECG 12-Lead ECG in standing position. QT/QTc intervals 525/509 msec.