Abstract 425 Poster Session IV, Tuesday, 5/4 (poster 199)

Bosma et al. (1981) described 2 unrelated males with severe hypoplasia of the nose and eyes, deficient taste and smell, inguinal hernias, hypogonadotropic hypogonadism with cryptorchidism, and normal intelligence. We report additional cases of this syndrome. Findings include: congenital bilateral microphthalmia, congenital arhinia, choanal atresia, cryptorchidism, hypogonadism, midface hypoplasia, and normal intelligence. During embryonic development, the nasal placodes form at 28 days postconception, as swellings which appear to invaginate to form the nasal chambers, as the edges of the placebo undergo cell replication and form the external nose. Medial and lateral nasal processes fuse with the maxillary processes to create the nasal tip, columella, and nasal alae, as well as portions of the upper lip and primary palate. Ectodermal epithelium from the roof of the nasal chambers forms olfactory nerves which reach the rhinencephalon by 41-44 days. After the process of external nasal development has been successfully completed, the choanae open into the posterior pharynx on day 44. Similar to nasal development, the optic vesicle makes contact with the overlying surface ectoderm at 26-27 days, and both layers invaginate. The eyes develop between 34 and 44 days, with closure of the anterior choroidal fissure on day 36, and closure of the posterior choroidal fissure at the optic nerve on day 44. In mice with homozygous mutations of Pax 6 (the "small eye" mutation), the nasal placodes fail to form and they have defective ocular and nasal development leading to underdevelopment of both structures. There is also a complicated network of developmentally regulated genes that function downstream of Pax 6 to form nasal, ocular and pituitary structures. In chick embryos, if the nasal placodes are removed at a time equivalent to 28 days in the human, the nose and nasal chambers fail to form. When the nasal placodes are transplanted elsewhere on the frontonasal process, ectopic nasal structures develop in these sites. With homozygous Pax 6 mutations in the mouse, in addition to the nasal placodes failing to form, there is also no Fgf 8 expression around the edges of where the nasal placodes should have formed. These genes represent candidate genes for this disorder. Recurrence of Bosma syndrome within families has been noted by Ruprecht and Majewski (1978), which suggests a genetic basis for this disorder. It is important to recognize infants with the Bosma Arhinia Anophthalmia Syndrome, since their facial features might easily be mistaken for suggesting the holoprosencephaly malformation sequence, which has a much poorer prognosis.