Congenital heart disease is one of the most common major malformations in humans, contributing substantially to the financial and psychological burden of child healthcare. About one percent of children are born with heart defects, and every year, more children die from congenital heart disease than are diagnosed with cancer. A diagnosis of congenital heart disease is frightening for parents, particularly when it affects a fragile newborn. The heart is the first organ to be matured in a human fetus and if a particular congenital heart defect is compatible with fetal life, the child will be born with a defective heart. More than 300 genetic syndromes are associated with congenital cardiac defects. In this review, we will discuss the genetics of congenital heart disease, how to carry out a diagnosis of the genetic causes and how to provide counseling for families with congenital heart disease.

Microscopic forms of karyotyping and cytogenetic analysis by means of G-banded chromosome analysis and rapid FISH (fluorescence in situ hybridization) on amniotic fluids or chorionic villus samples are at present regarded as the gold standard for prenatal diagnosis of chromosomal anomalies. Nevertheless, up to now the resolution of conventional chromosomal analysis was limited to approximately 4–5 Mb and not smaller than 2 Mb for FISH. Thus numerous common microdeletion syndromes are not detectable by conventional karyotyping. In addition, prenatal cells yield lower band resolution by conventional karyotyping than peripheral white blood cells making detection of subtle abnormalities even more difficult. With the advances in molecular-based techniques, a collaborative effort has led to the standardized method for detection of a restricted set of common chromosomal aneuploidies and microdeletion syndromes such as Down's syndrome, DiGeorge or Angelman syndrome either by rapid FISH and/or quantitative fluorescent PCR (QF-PCR). Even if the presence of particular phenotypic features of microdeletion or duplication syndromes may direct the use of syndrome-specific FISH tests in the postnatal period, syndrome-specific FISH analysis still has a very limited potential and application in the prenatal period due to the limitation in prenatal morphological or imaging diagnosis of many of the syndromes.

Skeletal anomalies occur with a frequency of around 1:500 and can present a diagnostic challenge when detected prenatally. Increasingly more sophisticated imaging such as MRI or CT may elucidate features more easily interpreted by postnatal radiologists. The aetiology of these anomalies is varied and includes aneuploidy, genetic syndromes, skeletal dysplasias, teratogens, disruption and maternal disease, making a multidisciplinary approach to the diagnosis essential. The estimated prevalence of skeletal dysplasias varies from 2–3/10,000 to 4–7/10,000 and diagnosis may require biochemical, cytogenetic, molecular genetic or haematological investigation. Clinical genetic input is often required as the family history or parental examination may yield valuable clues to the diagnosis. This review will briefly describe the normal embryology and sonographic appearances of fetal limb development and go on to suggest a systematic approach to the diagnosis of fetal skeletal dysplasias.

Corticosteroid treatment before preterm delivery was shown to be effective in reducing neonatal respiratory distress syndrome (RDS) more than three decades ago. The beneficial effect of steroids was further confirmed by Roberts and Dalziel's meta-analysis of 21 randomised controlled studies (RCT), which was published as a Cochrane Review in 2006. The authors concluded that the administration of a single course of steroids improved neonatal outcome, reducing RDS by 60%, periventricular haemorrhage (PVH) and necrotizing enterocolitis (NEC) by half, and neonatal death (NND) by 70%. However, these beneficial effects do not last for more than 7 days. Furthermore, steroids take at least 24 hours to be fully effective. Hence, it was advocated in the 1990's that regular weekly booster courses be given in order to maintain the therapeutic effects in high risk cases, as the timing of preterm birth cannot be readily predicted.