FOXE1 and Choanal Atresia, Cleft Palate, and Thyroid Agenesis

Abstract

Abstract The thyroid transcription factor-2 (TTF-2), more recently called FOXE1 (forkhead box E1), plays a crucial role in the development of ectodermand endoderm-derived structures, including the thyroid gland. Mice with complete disruption of the Titf2 gene exhibit either a sublingual or completely absent thyroid gland, together with cleft palate, thereby strongly suggesting a role for FOXE1 in promoting the migration process or in thyroid follicular differentiation as well as in palatal closure. The phenotypic manifestations of the knockout mice are consistent with the expression pattern of TTF2, which is found (1) in most of the foregut endoderm, including thyroid anlage, (2) in the craniopharyngeal ectoderm involved in palate formation, and (3) in the Rathke’s pouch. In humans, some homozygous missense mutations located in the forkhead domain of FOXE1 have been identi)ed in patients exhibiting a “complete” or “partial” Bamforth syndrome, characterized by thyroid agenesis, cleft palate and spiky hair, with choanal atresia and bi)d epiglottis in the complete phenotype. Taken together, these observations point to a key role for FOXE1 in human thyroid and palatal development. However, recent reports show that TTF2 mutations are rare in patients with thyroid dysgenesis and/or cleft palate, suggesting the involvement of other maybe downstream target genes. Therefore, more studies are needed to elucidate the genetic basis of Bamforth syndrome.