Genetics of Diaphragmatic Hernia

Abstract

Congenital diaphragmatic hernia (CDH) is a common birth defect with significant morbidity and mortality. Neurodevelopmental phenotypes, other congenital anomalies and dysmorphic features often co‐occur with CDH. Genetic causes of CDH include chromosomal anomalies, copy number variants and single gene disorders. Incomplete penetrance is common with some syndromes having CDH as a major feature while other syndromes are associated with a low but increased risk of developing CDH. A molecular cause is identified more often in individuals with syndromic CDH than in individuals with isolated CDH, and recommendations for genetic testing differ between the two groups. Current CDH research is focused on identifying additional genes that cause CDH and determining the molecular mechanisms by which perturbations in these genes lead to abnormal diaphragm development. Key Concepts Congenital diaphragmatic hernia (CDH) is associated with significant morbidity and mortality. Genetic causes of CDH include chromosomal anomalies, copy number variants and single gene disorders. A genetic cause is more often identified in individuals whose CDH co‐occurs with other anomalies (syndromic CDH) than in individuals with isolated CDH. Optimal genetic testing strategies vary between individuals with syndromic CDH and individuals with isolated CDH. Further research is needed to identify additional CDH genes and to determine their mechanisms of action.