Next Generation Sequencing after Invasive Prenatal Testing in Fetuses with Congenital Malformations: Prenatal or Neonatal Investigation.

Congenital malformations diagnosed by ultrasound screening complicate 3-5% of pregnancies and many of these have an underlying genetic cause. Approximately 40% of prenatally diagnosed fetal malformations are associated with aneuploidy or copy number variants, detected by conventional karyotyping, QF-PCR and microarray techniques, however monogenic disorders are not diagnosed by these tests. Next generation sequencing as a secondary prenatal genetic test offers additional diagnostic yield for congenital abnormalities deemed to be potentially associated with an underlying genetic aetiology, as demonstrated by two large cohorts: the 'Prenatal assessment of genomes and exomes' (PAGE) study and 'Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study' performed at Columbia University in the US.