Single gene disorders associated with congenital diaphragmatic hernia

Abstract

Congenital diaphragmatic hernia (CDH) is a common birth defect with a high pre- and postnatal mortality. Although the majority of diaphragmatic hernias occur as isolated malformations, additional major and minor anomalies are common and are present in more than 40% of patients. There are compelling data for the importance of genetic factors in the etiology of CDH, but the pathogenesis and the causative genes for CDH in humans remain elusive. There are more than 70 syndromes in which diaphragmatic hernias have been described, and several of these syndromes are single gene disorders for which the gene is known. One method for identifying the causative genes in isolated CDH is to study syndromes with known genes in which CDH is a recognized feature, with the rationale that those genes have a role in diaphragm development. This review discusses the syndromes that are most commonly associated with CDH, with greater attention towards syndromes in which the causative genes have been identified, including Simpson-Golabi-Behmel syndrome, Denys-Drash syndrome, spondylocostal dysostosis, craniofrontonasal syndrome, Cornelia de Lange syndrome and Marfan syndrome.