Nyegaard et al. (2012) studied a large 4-generation Swedish family with a history of ventricular arrhythmias, syncope, and sudden death, predominantly in association with physical exercise or stress. The proband was a 42-year-old man who first developed syncope ... Nyegaard et al. (2012) studied a large 4-generation Swedish family with a history of ventricular arrhythmias, syncope, and sudden death, predominantly in association with physical exercise or stress. The proband was a 42-year-old man who first developed syncope at 12 years of age while playing football; electrocardiogram (ECG) at that time showed bradycardia with a prominent U-wave in leads V2 and V3, without evidence of QT prolongation. He had a history of loss of consciousness on at least 4 occasions during physical activity and once in connection with a fire alarm. A 24-hour ECG recording revealed premature ventricular contractions (PVCs), bigeminy, and paired PVCs during football training, but no symptoms were reported. An older brother with a history of repeated syncope during exercise was reported to show polymorphic ventricular tachycardia on an exercise ECG; a follow-up ECG while on a beta-1 adrenergic receptor blocker showed PVCs at high loads. He had a son with syncope. The proband also had a brother who had drowned at 15 years of age during a swimming competition after prior episodes of syncope, and an older sister who had episodic syncope and was later found to have ventricular fibrillation, but stabilized on a beta-1 adrenergic receptor blocker and became asymptomatic. In addition, a younger sister presented at 7 years of age with repeated syncope during intense physical activity, and she also had a son with syncope. Their mother, who died at age 60, had multiple episodes of syncope in her youth for which she received medication. The proband's older sister had 6 children, 4 of whom were affected, including a son who died suddenly at 13 years of age while on a beta-1 adrenergic receptor blocker for syncopal episodes that had started at 2.5 years of age. A daughter, who began having syncope at 4 years of age and was asymptomatic on a beta-1 adrenergic receptor blocker, suffered cardiac arrest at age 16, was resuscitated, and received an implantable cardiac defibrillator (ICD). Two more daughters also presented with syncope within the first decade of life, and 1 had a son with syncope.
In a large 4-generation Swedish family with CPVT mapping to chromosome 14q31-q32, Nyegaard et al. (2012) identified a heterozygous missense mutation in the candidate gene calmodulin (CALM1; 114180.0001) that segregated fully with the disease and was not found ... In a large 4-generation Swedish family with CPVT mapping to chromosome 14q31-q32, Nyegaard et al. (2012) identified a heterozygous missense mutation in the candidate gene calmodulin (CALM1; 114180.0001) that segregated fully with the disease and was not found in 1,200 Danish controls. Analysis of CALM1 in 61 additional arrhythmia patients who were negative for mutation in the RYR2 gene revealed another heterozygous missense mutation (114180.0002), in an Iraqi woman with a history of syncope beginning at 4 years of age who ultimately underwent implantation of an ICD after cardiac arrest at age 15.