Two cases of agnathia (otocephaly): with review of the role of fibroblast growth factor (FGF8) and bone morphogenetic protein (BMP4) in patterning of the first branchial arch.

Agnathia (otocephaly) is a sporadic malformation characterized by agenesis of the mandible with characteristic dysmorphologic sequelae. We compare the prenatal presentations and dysmorphologic abnormalities of 2 female fetuses with agnathia. Fetus 1 was delivered at 33 weeks' gestational age and showed agnathia with characteristic sequelae of microstomia; microglossia; persistent buccopharyngeal membrane; and ventrally placed, malformed external ears. Fetus 2 was delivered at 32 weeks' gestational age and exhibited agnathia, astomia, and microglossia; in contrast to fetus 1, however, the external ears were laterally placed, low set, and malformed. For both fetuses, tridimensional computed tomographic scan showed the unique complete absence of the mandible. Additional malformations were documented and differed between the fetuses. We discuss the current molecular mechanisms implicated in 1st branchial arch patterning, particularly the impact of bone morphogenetic protein and fibroblast growth factor 8, and how these findings have the potential to explain the spectrum of abnormalities present in these 2 fetuses with agnathia without associated holoprosencephaly.