Summary
About 30 infants have been reported with bilateral anophthalmia or microphthalmia, and major cerebral malformations involving the hypothalamus and the pituitary stalk, and leading to multiple endocrine disturbances: diabetes insipidus, small stature by deficit in growth hormone, hypogonadism. Cleft palate, cleft lip and palate, ear anomalies, aplasia cutis were described as well. In one case the child also presented with an esophageal atresia. Cerebral MRI may reveal anomalies of midline structures : thick hypothalamus, narrow pituitary stalk, misshappen ventricles sometimes with thin cerebral cortex. Those children who survive the first year have psychomotor retardation and epilepsy. Almost all cases have been sporadic., although in 2 cases there was a family history of ocular anomaly. Mosaicism for a lethal gene has been suggested as an etiology for this syndrome, but the usual continuity and symmetry of the lesions make this hypothesis uncertain. Interestingly, in 3 of the reported cases with bilateral anophthalmia and hypothalamo-pituitary insufficiency, an interstitial deletion of chromosome 14q22 was discovered. It was suggested that the human BMP-4 gene, a growth factor member of the TGFb family, mapping to 14q22-q23, may play a role in pituitary and eye development. In the other cases of anophtalmia with midline defects, no interstitial deletion was described but one may expect that adequate cytogenetic techniques for microdeletion diagnosis may not have been applied in all cases. A male preponderance seems to exist, but the number of cases so far does not permit to conclude. *Author : Orphanet (February 2004).*
