Lahat et al. (2001) studied 41 members of 7 families from a highly inbred Bedouin tribe in northern Israel, in which 9 children had unexplained sudden death, 7 during vigorous exercise and 2 during excitement. In addition, 12 ... Lahat et al. (2001) studied 41 members of 7 families from a highly inbred Bedouin tribe in northern Israel, in which 9 children had unexplained sudden death, 7 during vigorous exercise and 2 during excitement. In addition, 12 other children had onset of recurrent syncope and seizures at around 6 years of age, with 70% of the episodes occurring during vigorous physical activity and 30% following sudden excitement. The parents of affected children were all related and were all asymptomatic. Affected individuals exhibited a relative resting bradycardia and mild prolongation of the QTc segment compared to unaffected sibs; polymorphic ventricular tachycardia (PVT) was inducible by treadmill or isoproterenol infusion in all affected individuals and 1 asymptomatic sib, appearing at a mean sinus rate of 110 bpm. Mean age at onset was 7 years, with penetrance of 100% by age 10 years and a high mortality rate when left untreated. Di Barletta et al. (2006) reported a 6-year-old boy with a history of effort-induced syncopal episodes from 3 years of age, in whom exercise stress testing demonstrated rapid PVT; Holter monitoring showed several runs of asymptomatic polymorphic and bidirectional sustained VT at rates of 170 to 180 bpm during outdoor play. The authors also described an unrelated 17-year-old girl with onset of syncopal episodes at 4 years of age and PVT of up to 200 bpm on ECG, in whom antiarrhythmic therapy and left cardiac sympathetic denervation were unsuccessful and who ultimately required an implantable cardioverter defibrillator. Family history was negative in both cases.
Lahat et al. (2001) analyzed the CASQ2 gene in members of 7 consanguineous Bedouin families in Israel with CPVT and identified homozygosity for a mutation (N307H; 114251.0001) in all affected individuals.
Di Barletta et al. (2006) ... Lahat et al. (2001) analyzed the CASQ2 gene in members of 7 consanguineous Bedouin families in Israel with CPVT and identified homozygosity for a mutation (N307H; 114251.0001) in all affected individuals. Di Barletta et al. (2006) analyzed the CASQ2 gene in a 6-year-old boy and an unrelated 17-year-old girl with CPVT and identified homozygosity for a 16-bp deletion (114251.0002) and compound heterozygosity for the 16-bp deletion and a missense mutation (114251.0003), respectively. Parental consanguinity was denied in both families, and nonconsanguinity was confirmed by haplotype analysis. None of 11 heterozygous carriers identified in the 2 families developed ventricular arrhythmias.