SOX2 mutations cause bilateral anophthalmia in an autosomal dominant pattern in humans. Some extraocular features may be associated, including brain malformations, male genital tract malformations, postnatal growth retardation, and facial dysmorphic features. In addition seizures, motor abnormalities and learning disabilities can be present. We report here familial recurrence of a strikingly variable clinical presentation of the SOX2 phenotype in two girls. Both had a c. 70_86del SOX2 mutation and their mother had germinal mosaicism. The phenotype of the first affected child has been previously reported [Menetrey et al., 2002]. Briefly, she presented at birth with short palpebral fissures and closed eyelids, with no palpable eyeball. CT scan and post-mortem necropsy confirmed bilateral anophthalmia. She had type III esophageal atresia, and diagnosis of AEG syndrome (Anophthalmia, Esophageal atresia, Genital abnormalities, MIM (206900) was made.

During her mother’s subsequent pregnancy, an ultrasound scan examination detected severe and progressive triventricular hydocephalus. The pregnancy was interrupted at the 20th week. Autopsy of the female fetus demonstrated stenosis of the aqueduct of Sylvius, associated with corpus callosum hypoplasia, and identified the presence of 11 rib