Prenatal Isolated Congenital Diaphragmatic Hernia: A Rare Clinical Presentation of a <i>GATA4</i> Pathogenic Variant

Congenital diaphragmatic hernia is a genetically heterogeneous condition with a developmental defect in the diaphragm. The <i>GATA4</i> gene is essential for fetal heart development, and pathogenic <i>GATA4</i> variants are a known cause of structural congenital heart diseases. Haploinsufficiency of GATA4 is also associated with diaphragmatic hernia. Pathogenic <i>GATA4</i> sequence variants with isolated diaphragmatic hernia in the absence of congenital heart defects are extremely rare. Our report expands the phenotypic spectrum related to <i>GATA4</i>.We report a fetus with a prenatal isolated diaphragmatic hernia detected during a routine screening ultrasound. An autopsy of the fetus confirmed a large isolated posterolateral hernia, which affected the left lung volume significantly. Clinical exome sequencing revealed a novel heterozygous nonsense variant c.826C>T,p.(Gln276*) in the <i>GATA4</i> gene, which was predicted to cause haploinsufficiency. The variant occurred <i>de novo</i> and was classified as pathogenic.The report presents a detailed clinical description of the fetus with ultrasound, MRI, and post-mortem pictures of a rare prenatal isolated diaphragmatic hernia related to a novel pathogenic <i>GATA4</i> sequence variant. Prenatal ultrasound screening with further investigation by MRI and a comprehensive gene panel holds a key role in determining the prognosis of a fetus with a diaphragmatic hernia.