Abstract 2202: Clinical and Electrocardiographic Characteristics of Genotype-Unknown Patients with Congenital Long-QT Syndrome
Background: Genotype-phenotype correlations have been rigorously investigated in genotyped patients with congenital long-QT syndrome (LQTS), whereas those of genotype-unknown LQTS patients are poorly understood.
Methods: We conducted molecular screening for KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and KCNJ2 genes in 136 probands clinically affected with congenital LQTS, and identified a KCNQ1 mutation in 34 probands (LQT1), a KCNH2 mutation in 37 probands (LQT2), an SCN5A mutation in 6 probands (LQT3), and a KCNJ2 mutation in 5 probands (LQT7). However, no responsible mutations were identified in the remaining 54 probands (40%). We retrospectively evaluated clinical characteristics including the incidence and triggers for cardiac events and the family history, electrocardiographic parameters, treatment, and clinical course in the 54 genotype-unknown probands, and compared them with those in the 3 major genotypes, 34 LQT1, 37 LQT2 and 6 LQT3 probands.
Results: Among the 54 probands (35 females, 25±16 years), 26 patients (48%) experienced cardiac events (19 syncope only, 73%, 7 aborted cardiac arrest or unexpected sudden cardiac death, 27%), and the event rate was significantly lower than that in the LQT2 probands (32/37, 86%, p=0.001). Mean age of first cardiac event was 20±14 years. Cardiac events principally occurred during mental stress or auditory stimuli (40%), and equally less during exercise (27%) or during sleep/rest (20%). Only 12 probands (22%) had family history of definite LQTS (Schwartz score ≥ 4). Mean corrected QT (QTc) interval was 475±51 ms, which was shorter than those in either the LQT2 probands (509±42 ms; p=0.016) or the LQT3 probands (520±28 ms; p=0.04). Low-amplitude and notched T waves were seen in 15 probands (28%). β-Blockers were prescribed in 26 probands (48%), and effective to reduce cardiac events in 14 (53%), being comparable to the effective rate in the LQT2 probands (21/31, 68%). ICD was implanted in 2 probands.
Conclusions: The QTc interval was shorter and family history was fewer in genotype-unknown LQTS probands, whose clinical characteristics including trigger of cardiac events, T wave morphology, and effectiveness of β-blockers seem to be similar to those of LQT2 syndrome.