LQTS mosaicism implicated in recurrent miscarriage

Maternal mosaicism for lethal long-QT syndrome mutations is a previously 
unrecognized cause of recurrent late-term fetal loss. 

Source: Circulation 2004; 109: 3029-34
Posted: 24 June 2004

US clinicians have reported the case of a woman in whom recurrent third-trimester 
fetal loss is attributed to maternal mosaicism for long-QT syndrome (LQTS), in a 
communication that has important implications for genetic counseling. 

LQTS has been recently recognized as a cause of sudden infant death syndrome but 
has not been previously linked to late-term fetal loss. Dominant mutations 
underlying LQTS are often assumed to have arisen de novo, while the possibility 
of genetic mosaicism is rarely explored. 

Tod Miller (University of Miami School of Medicine, Florida, USA) and colleagues 
describe the case of a woman who experienced late-term fetal loss (7 months) or 
near loss in three successive pregnancies. Each fetus showed evidence of cardiac 
decompensation, with the single surviving infant exhibiting LQTS and ventricular 
tachycardia.

Genetic analysis of the surviving infant revealed a heterozygous mutation in the 
cardiac sodium channel, SCN5A, that has been previously associated with LQTS. At 
first look, the mutation was not detected in the mother but closer analysis 
found it in up to 10 percent of her cells. Cord blood from the third fetus also 
harbored the mutation.   
   
"The distinction between de novo mutation and parental germ-line mosaicism is 
critical because mosaicism confers a considerably higher risk of disease 
recurrence in subsequent pregnancies," Miller et al warn.