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The 2011 challenge in considering a diagnosis of long-QT syndrome (LQTS) is best viewed as having 4 distinct clinical scenarios. The first and most straightforward is the family member with a genotyped kindred in whom, within a month, a relatively firm diagnosis can be obtained by family-specific testing, along with an ECG. The second, the genotype-negative index patient with otherwise unexplained, repeated, markedly prolonged QTc (>480), is similarly straightforward. The third scenario comprises family members of those same patients with unambiguous LQTS but no available gene. For those patients, their prior probability of having LQTS is estimated by careful pedigree analysis, with ECG findings combined with other clinical evaluation to help characterize the potential phenotype. The likelihood of making the diagnosis is relatively large (50%, 25%, 12.5%), depending on distance from an affected individual. The most challenging scenario is the young person with the “borderline” test obtained either for unrelated symptoms or during screening efforts before sports or medication without a clear family history. For that patient, the prior probability of having LQTS may as low or lower than the estimated gene prevalence of ≈1 in 2000 (0.05%).1 Indeed, in that setting, even genetics sometimes leaves the clinicians challenged when the result returns with a variant of unknown significance, requiring further pedigree analysis. In that context, the careful descriptive study of exercise QT dynamics by Berger and colleagues2 in this issue of Circulation: Arrhythmia and Electrophysiology adds useful information to this challenge.Article see p 448The study itself is straightforward: 94 boys …

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