Alternative titles; symbols
ORPHA: 3286; DO: 0060676;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p13.1 | Ventricular tachycardia, catecholaminergic polymorphic, 2 | 611938 | Autosomal recessive | 3 | CASQ2 | 114251 |
A number sign (#) is used with this entry because of evidence that catecholaminergic polymorphic ventricular tachycardia-2 (CPVT2) is caused by homozygous or compound heterozygous mutation in the gene encoding calsequestrin-2 (CASQ2; 114251) on chromosome 1p13.
For a general phenotypic description and a discussion of genetic heterogeneity of CPVT, see 604772.
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.
The transmission pattern of CPVT2 in the families reported by Lahat et al. (2001) was consistent with autosomal recessive inheritance.
Lahat et al. (2001) performed genomewide linkage analysis in 7 consanguineous Bedouin families segregating catecholamine-induced PVT in an autosomal recessive fashion and mapped the disease locus to a 16-Mb interval on chromosome 1p21-p13, with a maximum lod score of 8.24 obtained at D1S189 (theta = 0).
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.
di Barletta, M. R., Viatchenko-Karpinski, S., Nori, A., Memmi, M., Terentyev, D., Turcato, F., Valle, G., Rizzi, N., Napolitano, C., Gyorke, S., Volpe, P., Priori, S. G. Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia. Circulation 114: 1012-1019, 2006. [PubMed: 16908766] [Full Text: https://doi.org/10.1161/CIRCULATIONAHA.106.623793]
Lahat, H., Eldar, M., Levy-Nissenbaum, E., Bahan, T., Friedman, E., Khoury, A., Lorber, A., Kastner, D. L., Goldman, B., Pras, E. Autosomal recessive catecholamine- or exercise-induced polymorphic ventricular tachycardia: Clinical features and assignment of the disease gene to chromosome 1p13-21. Circulation 103: 2822-2827, 2001. [PubMed: 11401939] [Full Text: https://doi.org/10.1161/01.cir.103.23.2822]
Lahat, H., Pras, E., Olender, T., Avidan, N., Ben-Asher, E., Man, O., Levy-Nissenbaum, E., Khoury, A., Lorber, A., Goldman, B., Lancet, D., Eldar, M. A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. Am. J. Hum. Genet. 69: 1378-1384, 2001. [PubMed: 11704930] [Full Text: https://doi.org/10.1086/324565]