CLINICAL STUDY: GENETICS AND ARRHYTHMIAS
Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death
Early diagnosis of asymptomatic carriers
Barbara Bauce, MD, PhD*,
Alessandra Rampazzo, BSc, PhD ,
Cristina Basso, MD, PhD ,
Alessia Bagattin, BSc,
Luciano Daliento, MD*,
Natascia Tiso, BSc, PhD,
Pietro Turrini, MD, PhD,
Gaetano Thiene, MD,
Gian Antonio Danieli, BSc and
Andrea Nava, MD*,*
* Department of Cardiology, University of Padua Medical School, Padua, Italy
Department of Biology, University of Padua Medical School, Padua, Italy
Department of Pathology, University of Padua Medical School, Padua, Italy
Manuscript received November 13, 2001;
revised manuscript received April 1, 2002,
accepted April 19, 2002.
* Reprint requests and correspondence: Andrea Nava, MD, c/o Associazione Ricerche Cardiopatie Aritmiche, Via A. Gabelli, 86-35121, Padua, Italy.
andrea.nava{at}unipd.it
OBJECTIVES: We sought to establish the role of genetic screening for ryanodine receptor type 2 (RyR2) gene mutations in families with effort-induced polymorphic ventricular arrhythmia (PVA), syncope and juvenile sudden death.
BACKGROUND: The RyR2 mutations have been associated with PVA, syncope and sudden death in response to physical or emotional stress.
METHODS: We studied 81 subjects (39 males and 42 females; mean age 31 ± 20 years) belonging to eight families with pathogenic RyR2 mutations. All subjects underwent screening for RyR2 mutations, electrocardiography (ECG), 24-h Holter monitoring, signal-averaged electrocardiography (SAECG), two-dimensional echocardiography and exercise stress testing. Electrophysiologic (EP) study was performed in nine patients.
RESULTS: Six different RyR2 mutations were found in eight families. Forty-three family members carried the gene mutation. Of these, 28 (65%) showed effort-induced arrhythmic symptoms or signs and one died suddenly during follow-up. Family history revealed 19 juvenile cases of sudden death during effort or emotion. In two families sharing the same mutation, no subject presented with PVA during the stress test; thus, sudden death and syncope were the only clinical manifestations. The 12-lead ECG was normal in all but two subjects, whereas five patients showed positive late potentials on the SAECG. In 17 (39.5%) of 43 subjects, the two-dimensional echocardiogram revealed localized kinetic abnormalities and mild structural alterations of the right ventricle. The EP study was not able to induce PVA.
CONCLUSIONS: The absence of symptoms and PVA on the stress test in more than one-third of carriers of RyR2 mutations, as well as the lack of PVA inducibility by the EP study, underlies the importance of genetic screening for the early diagnosis of asymptomatic carriers and prevention of sudden death.
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Abbreviations and Acronyms
| | ARVD2 | | arrhythmogenic right ventricular dysplasia (cardiomyopathy) type 2 | | DNA | | deoxyribonucleic acid | | ECG | | electrocardiogram/electrocardiographic | | EP | | electrophysiologic | | PCR | | polymerase chain reaction | | PVA | | polymorphic ventricular arrhythmia | | RV | | right ventricle/ventricular | | RyR2 | | ryanodine receptor type 2 | | SAECG | | signal-averaged electrocardiography |
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