Prenatal Diagnosis of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins in Fetuses Presenting with Extrapulmonary Anomalies: Three Case Reports

Abstract Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare and fatal developmental disorder of the lungs that manifests severe clinical symptoms in newborns. In this study, we present three cases of ACDMPV that showed extrapulmonary a nonspecific prenatal phenotype. In Case 1, routine anatomical scanning revealed fetal megacystis. Subsequent amniocentesis detected a pathogenic deletion of 1.17 Mb in the 16q24.1 region, encompassing the FOXF1 gene. In Case 2, second-trimester ultrasound examination showed fetal bowel dilatation and polyhydramnios at 27 weeks gestation. Trio exome sequencing (ES) identified a de novo FOXF1 c. 226C > T (p. Gln76Ter) variant. In Case 3, the routine ultrasound revealed moderate fetal tricuspid regurgitation at 22 weeks. Trio ES identified a de novo c. 356G > A (p. Gly119Asp) variant in FOXF1. Our study indicates that given the challenges associated with detecting ACDMPV via ultrasound examination alone, there is a pressing need for broader implementation of prenatal genetic testing to facilitate early diagnosis in fetuses with structural anomalies, especially involving the genitourinary, gastrointestinal, or cardiovascular systems.