From Multiple Congenital Anomalies to Pituitary Gland Malformation: Wide Spectrum of Clinical Features in a Family With FOXA2 Variant

FOXA2 (hepatocyte nuclear factor-3β, HNF-3β) encodes a transcriptional activator involved in early embryogenesis, particularly in the patterning and differentiation of midline structures such as the neural tube, foregut, and pituitary gland. Its role in human pathogenesis was first suspected when patients with deletion of chromosome 20p11.2 which encompassed the FOXA2 gene were reported. With improvement in molecular diagnosis, patients with variants in FOXA2 genes have more recently been described with pituitary dysfunction, hypoglycemia, craniofacial, and/or endoderm-derived organ malformations; however, they are still rare. Here, we report a family who experienced fetal loss due to multiple congenital anomalies identified with FOXA2 gene, NM_021784.5(FOXA2):c.429C>A (p.Tyr143Ter). Further segregation analysis of this variant identified the presence of the same variant in the father of the fetus, who himself had a history of growth hormone deficiency and pituitary malformation. We report for the first time the varying degrees of severity of disorder most likely attributed to variant in FOXA2 gene within the same family.