Sudden arrhythmic death syndrome: familial evaluation identifies inheritable heart disease in the majority of families.
OBJECTIVE
At least 4% of sudden deaths are unexplained at autopsy [sudden arrhythmic death syndrome (SADS)] and a quarter may be due to inherited cardiac disease. We hypothesized that comprehensive clinical investigation of SADS families would identify more susceptible individuals and causes of death.


RESULTS
Fifty seven consecutively referred families with SADS death underwent evaluation including resting 12 lead, 24 h and exercise ECG and 2D echocardiography. Other investigations included signal averaged ECG, ajmaline testing, cardiac magnetic resonance imaging, and mutation analysis. First-degree relatives [184/262 (70%)] underwent evaluation, 13 (7%) reporting unexplained syncope. Seventeen (30%) families had a history of additional unexplained premature sudden death(s). Thirty families (53%) were diagnosed with inheritable heart disease: 13 definite long QT syndrome (LQTS), three possible/probable LQTS, five Brugada syndrome, five arrhythmogenic right ventricular cardiomyopathy (ARVC), and four other cardiomyopathies. One SCN5A and four KCNH2 mutations (38%) were identified in 13 definite LQTS families, one SCN5A mutation (20%) in five Brugada syndrome families and one (25%) PKP2 (plakophyllin2) mutation in four ARVC families.


CONCLUSIONS
Over half of SADS deaths were likely to be due to inherited heart disease; accurate identification is vital for appropriate prophylaxis amongst relatives who should undergo comprehensive cardiological evaluation, guided and confirmed by mutation analysis.
Behr
Elijah R
ER
Cardiac and Vascular Division, St George's University of London, Cranmer Terrace, London SW17 0RE, UK. ebehr@sgul.ac.uk
Dalageorgou
Chrysoula
C
Christiansen
Michael
M
Syrris
Petros
P
Hughes
Sian
S
Tome Esteban
Maria T
MT
Rowland
Edward
E
Jeffery
Steve
S
McKenna
William J
WJ
D000328:Adult; D000465:Algorithms; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D009202:Cardiomyopathies / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree