Contribution of long-QT syndrome genetic variants in sudden infant death syndrome.
A cohort of 52 French unrelated infant cases who died unexpectedly before they reached 12 months of age was blindly investigated to better quantify the contribution of long-QT syndrome (LQTS) genetic variants in French cases of sudden infant death syndrome (SIDS). After a standardized autopsy protocol, a blinded molecular screening of the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes was performed on each case. These postmortem investigations enabled us to reclassify 18 as non-SIDS cases, 32 as SIDS cases, and 2 as suspected SIDS cases. Among the 18 non-SIDS cases, no LQTS mutation was identified. In contrast, our results led to a possible explanation for the death of at least three infants in the SIDS cohort. Half of the LQTS gene variants identified were located on the SCN5A gene. This study confirms that LQTS mutations may represent one of the leading genetic causes of SIDS. If autopsy fails to provide an explanation for an unexplained infant death, medicolegal investigation should be extended with a molecular screening of major LQTS genes. Identification of more LQTS mutations in SIDS cases could provide new insights into the pathophysiology of SIDS and, consequently, reduce the number of unexplained sudden infant deaths.
Millat
Gilles
G
Laboratoire de Cardiogénétique Moléculaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, Bron Cedex, France. gilles.millat@chu-lyon.fr
Kugener
Béatrice
B
Chevalier
Philippe
P
Chahine
Mohamed
M
Huang
Hai
H
Malicier
Daniel
D
Rodriguez-Lafrasse
Claire
C
Rousson
Robert
R