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Background— The prevalence of genetic arrhythmogenic diseases is unknown. For the long-QT syndrome (LQTS), figures ranging from 1:20 000 to 1:5000 were published, but none was based on actual data. Our objective was to define the prevalence of LQTS. Methods and Results— In 18 maternity hospitals, an ECG was performed in 44 596 infants 15 to 25 days old (43 080 whites). In infants with a corrected QT interval (QTc) >450 ms, the ECG was repeated within 1 to 2 weeks. Genetic analysis, by screening 7 LQTS genes, was performed in 28 of 31 (90%) and in 14 of 28 infants (50%) with, respectively, a QTc >470 ms or between 461 and 470 ms. A QTc of 451 to 460, 461 to 470, and >470 ms was observed in 177 (0.41%), 28 (0.06%), and 31 infants (0.07%). Among genotyped infants, disease-causing mutations were found in 12 of 28 (43%) with a QTc >470 ms and in 4 of 14 (29%) with a QTc of 461 to 470 ms. One genotype-negative infant (QTc 482 ms) was diagnosed as affected by LQTS on clinical grounds. Among family members of genotype-positive infants, 51% were found to carry disease-causing mutations. In total, 17 of 43 080 white infants were affected by LQTS, demonstrating a prevalence of at least 1:2534 apparently healthy live births (95% confidence interval, 1:1583 to 1:4350). Conclusions— This study provides the first data-based estimate of the prevalence of LQTS among whites. On the basis of the nongenotyped infants with QTc between 451 and 470 ms, we advance the hypothesis that this prevalence might be close to 1:2000. ECG-guided molecular screening can identify most infants affected by LQTS and unmask affected relatives, thus allowing effective preventive measures.

Background. The long QT syndrome (LQTS), a leading cause of sudden death under 20 years of age, is due to mutations in genes which encode ion channels involved in the control of ventricular repolarization. In a prospective study on 34,000 neonates we found that a prolonged QT interval was associated with a 41 times greater risk for sudden infant death syndrome (SIDS) and, recently, in a case-control study on 201 cases of SIDS we found disease-causing LQTS mutations in 9.5% of the victims. Based on these results the Italian Ministry of Health is considering the possibility of introducing in the National Health Service an electrocardiographic (ECG) screening program in the first month of life to identify infants affected by LQTS. A realistic assessment of the prevalence of infants with LQTS becomes necessary. Methods. An ECG was recorded in the first month of life in 44,596 neonates. The QT interval was measured and corrected for heart rate according to the Bazett’s formula (QTc). In the neonates with a markedly prolonged QT (QTc ≥ 470 msec) molecular screening of the LQTS genes was performed. Results. A QTc between 440 and 470 msec was observed in 611 neonates (1.4%). A QTc ≥ 470 ms was found in 31 neonates (0.07%). Genetic analysis was performed in 28/31 (90%) neonates and LQTS mutations were identified in 14 of them (50%): 8 were LQT1, 4 LQT2 and 2 LQT3. Besides one de novo mutation, all other cases were familial and genetic analysis identified additional family members (37/72, 51%) affected by LQTS who had not been previously diagnosed. Within these 28 infants QTc was longer in the positively genotyped neonates (493±22 vs 479±6 ms, p=0.037) and a LQTS mutation was identified in all the neonates (n=5) with a QTc > 496 ms. Conclusions. An ECG performed in the first month of life, with genetic analysis in selected cases, allows early diagnosis of infants with sporadic and familial forms of LQTS, thus leading to institution of effective therapies aimed at preventing sudden death either in infancy or later on in life, not only in the neonates but also in their affected family members. This study also provides a first data-based estimate of LQTS prevalence, likely to be between 1/3,000 and 1/2,500 live births.