Congenital heart malformations: aetiology and associations

The causes of congenital heart malformations are complex and include a major contribution by genetic factors. These can be considered under the headings of chromosomal, single gene and multifactorial. Almost any degree of autosomal imbalance, whether a full trisomy or a tiny microdeletion, can cause a cardiac malformation. Recent research has identified several developmental genes which play an important role in cardiac formation: these are discussed with regard to laterality, septation and vascular morphogenesis. Hypothetical 'polygenes', which may contribute to non-syndromal 'multifactorial' cardiac malformations have yet to be identified. Well-known cardiac malformation syndrome associations are described and simple guidelines are presented to help in the assessment and investigation of an affected neonate who has additional multiple dysmorphic features.