Clinical Characterization
Of the six patients with chromosomal deletions harboring FOXF1 (D1–D6), five (D1 and D3–D6) died from pulmonary insufficiency in the first two months of life, and the mother of a sixth (D2) underwent elective termination of pregnancy at 22 weeks. Three patients (D1, D3, and D4) had ACD/MPV documented by histopathological examination (Figure 2A). Two other patients (D5 and D6) had severe respiratory distress, raising the possibility of ACD/MPV, but no postmortem examination was performed. Cardiac malformations were present in five of the six patients; two patients (D2 and D4) had a hypoplastic left heart, and a third (D5) had a small left ventricle. One patient (D1) manifested esophageal atresia with tracheo-esophageal fistula, whereas duodenal and anal atresias were present in another patient (D3). Five patients (D2–D6) had abnormalities consistent with urinary tract obstructive lesions, ranging from uretero-pelvocaliectasis to severe hydronephrosis. The phenotype in patient D7 was clearly distinct from that in the other six patients. This patient did not have respiratory insufficiency in the neonatal period and was still alive at the age of 3 years, having presented with atrial septal defect, bilaterally dilated and tortuous ureters with left hydronephrosis, diastasis recti, and developmental delay (Figure 2A and Table 1). The deletion was inherited from the patient's mother, whose sole recognized phenotypic abnormality was the presence of an umbilical hernia.