Exome sequencing in the assessment of congenital malformations in the fetus and neonate

Major congenital anomalies are often associated with perinatal mortality, long-term morbidity and prolonged hospitalisation. Prenatal ultrasound remains the principle diagnostic test for many anomalies, but despite this up to one-third are only identified in the neonatal period. The primary step in determining underlying aetiology is to define accurately the phenotype by recognition of dysmorphology (both prenatally and postnatally). The potential introduction of next-generation sequencing, primarily through exome sequencing, into perinatal practice may improve the pathological diagnostic yield. However, clinicians must understand both the benefit and potential harms of this technology in facilitating the discovery of relevant pathogenic variants in the diagnosis and management of congenital malformations.