OBJECTIVES: The purpose of this study was to investigate the follow-up and 
treatment of the mutation-carrying relatives of a proband with an inherited 
arrhythmia syndrome.
BACKGROUND: The congenital long QT syndrome (LQTS), catecholaminergic 
polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) are 
primary inherited arrhythmia syndromes that may cause syncope and sudden cardiac 
death in young individuals. After establishing the disease-causing 
deoxyribonucleic acid (DNA) mutation in probands, we actively conducted cascade 
screening to identify, most often asymptomatic, relatives who are also at risk 
of life-threatening arrhythmias.
METHODS: We retrospectively collected data from our cardiogenetics database and 
patient records and analyzed whether the identified carriers received 
prophylactic treatment.
RESULTS: From 1996 to 2008, 130 probands with a disease-causing mutation in one 
of the involved genes were identified, and 509 relatives tested positive for the 
disease-causing familial mutation. These subjects subsequently underwent 
cardiologic investigation (electrocardiography, exercise testing, Holter 
monitoring, ajmaline testing, echocardiography, where appropriate). After a mean 
follow-up of 69 +/- 31 months (LQTS), 60 +/- 19 months (CPVT), and 56 +/- 21 
months (BrS), treatment was initiated and ongoing in 65% (199 of 308), 71% (85 
of 120), and 6% (5 of 81) of the relatives in the LQTS, CPVT, and BrS families, 
respectively. Eight carriers were lost to follow-up. Treatment included drug 
treatment (n = 249) or implantation of pacemakers (n = 26) or 
cardioverter-defibrillators (n = 14). All mutation carriers received lifestyle 
instructions and a list of drugs to be avoided.
CONCLUSIONS: Cascade screening in families with LQTS, BrS, or CPVT, which was 
based on DNA mutation carrying and subsequent cardiologic investigation, 
resulted in immediate prophylactic treatment in a substantial proportion of 
carriers, although these proportions varied significantly between the different 
diseases.