Peter Benn
UCONN Health, USA
Title: Prenatal screening for 22q11.2 Deletion Syndrome: an opportunity to improve neonatal management for a common cause of congenital cardiac defects
Biography
Biography: Peter Benn
Abstract
The 22q11.2 Deletion Syndrome (22q11.2DS) Is associated with a variably expressed complex phenotype that includes cardiac abnormalities that are present in approximately 74% of cases. A high proportion of conotruncal and right aortic arch malformations are attributable to 22q11.2DS. Prenatal prevalence may be as high as 1 in 1000 fetuses.We developed a non-invasive prenatal screening test for 22q11.2DS and 4 other clinically significant microdeletion syndromes based on analysis of single-nucleotide polymorphisms in maternal cell-free DNA. In 80,449 pregnancies screened for 22q11.2 deletions, we found 263 (0.39%) at high-risk for fetal deletion and 6 (1 in 13,408) maternal carriers. Pregnancy outcome information was available in 153 pregnancies at high-risk for a fetal deletion of which 24 were true-positive. The testing had a positive predictive value of 15.7%, a false-positive-rate of 0.33%, and the estimated prevalence of 22q11.2DS was 1/1255 in the referral population. Of the 24 true-positives, 21 showed prenatal ultrasound abnormalities including 10 with Tetralogy of Fallot, 3 unspecified cardiac malformations, 1 truncus arteriosis, 1 double outlet right ventricle and 1 VSD. A screening enhancement has reduced the false-positive rate to 0.07% and increased the positive predicative value to 44.2%.Screen-positive pregnancies need to be confirmed by chromosome microarray, either on a prenatal sample (amniotic fluid or chorionic villus) or at birth (blood). Prenatal screening provides an opportunity to reduce adverse sequelae in 22q11.2DS through delivery at a tertiary medical center, the earliest possible management of cardiac, velopharyngeal, and other malformations, seizure management, and additional specialty consultation.