Dynamic analysis of the QT interval in long QT1 syndrome patients with a normal phenotype

Aims In families with the long QT syndrome penetrance may be low: up to 70% of gene carriers may have a normal QTc interval. These patients require th erapy, similar to that in those with longer QTc intervals, but identifying them, using molecular analysis, is difficult to apply on a large scale. A l arge French family affected by the long QT1 syndrome was followed-up over a 25-year period. In adult males but not in females. the QTc interval normal ized after puberty. We aimed to find clinical criteria, based on ambulatory ECG recordings so that we could improve diagnosis in affected members with a normal QTc. Methods and Results Linkage analysis and direct sequencing were an indicato r of the long QT1 gene in our family. Reverse transcription-polymerase chai n reaction analysis demonstrated abnormal transcripts in lymphocytes from s ilent gene carriers. The functional profile of mutated protein isoforms was investigated using the patch-clamp technique. Dynamic analysis of ventricu lar depolarization was conducted using Holter recordings in patients, and i n sex- and age-matched controls, Circadian variations of the QTc interval a nd the QT/RR relationship were assessed. Sensitivity, specificity, and pred ictive values were evaluated for proposed clinical criteria, We found that dynamic analysis of the QT interval permitted individual diagnosis in mutat ion carriers even when the QTc interval was normal (adult males). Conclusion Dynamic analysis of the QT interval is of diagnostic value in th e long QT1 syndrome in patients with a normal phenotype, Clinical implicati ons include improvement in screening and patient management. (Eur Heart J 2 001; 22: 410-422, dsi:10.1053/ euhj,2000,2292) (C) 2001 The European Societ y of Cardiology.