ß 2006 Wiley-Liss, Inc. American Journal of Medical Genetics 140A:636–639 (2006) Research Letter Recurrence of SOX2 Anophthalmia Syndrome With Gonosomal Mosaicism in a Phenotypically Normal Mother Laurence Faivre, 1 * Kathleen A. Williamson, 2 Vale ´rie Faber, 3 Nicole Laurent, 4 Marianne Grimaldi, 3 Christel Thauvin-Robinet, 1 Christine Durand, 5 Francine Mugneret, 6 Jean-Bernard Gouyon, 3 Alain Bron, 7 Fre ´de ´ric Huet, 3 Caroline Hayward, 2 Veronica van Heyningen, 2 and David R. FitzPatrick 2 1 Centre de Ge ´ne ´tique, Ho ˆpital d’Enfants, Dijon, France 2 MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom 3 Service de Pe ´diatrie, Ho ˆpital d’enfants, Dijon, France 4 Service d’Anatomopathologie, CHU le Bocage, Dijon, France 5 Service de Radiologie, Ho ˆpital d’Enfants, Dijon, France 6 Service de Cytoge ´ne ´tique, CHU Le Bocage, Dijon, France 7 Service d’Opthalmologie, CHU Le Bocage, Dijon, France Received 23 April 2005; Accepted 27 November 2005 To the Editor: Bilateral anophthalmia is a rare ocular malformation that appears to be etiologically heterogeneous. Anophthalmia may be seen as a component of recognizable syndromes [Bermejo and Martinez-Frias, 1998], of chromosomal abnormalities [Chitayat et al., 1996], or associated with other features without a known entity [Tucker et al., 1996]. Mendelian forms of anophthalmia can be inherited following an auto- somal recessive, autosomal dominant, or X-linked inheritance [Morrison et al., 2002]. De novo SOX2 mutations have been shown to cause 10–20% of severe bilateral eye malformations [Fantes et al., 2003; Ragge et al., 2005]. The ocular phenotype included anophthalmia or microphthalmia, in some cases associated with optic nerve or chiasma abnormalities. The presence of extraocular features permitted to define a SOX2 anophthalmia syndrome characterized by neurological abnormalities (psychomotor delay, myopathy, spastic diplegia, seizures, microcephaly, and sensorineural deafness) and/or external genitalia abnormalities [Ragge et al., 2005]. Here we report on the first likely case of gonosomal mosaicism for a SOX2 mutation resulting in recur- rence of anophthalmia/microphthalmia spectrum within a sibship. Both reported cases were the results of the second and sixth pregnancies of a healthy non-consanguineous couple that originated from Morocco. Ophthalmological examinations of both parents with normal refraction studies and the four healthy offsprings were normal. Case 1, a female fetus was examined following a termination of pregnancy at 17 weeks of gestation due to severe hydrocephaly detected on fetal ultrasound. Autopsy revealed the length and weight to be normal for gestational age, but a significantly increased occi- pito-frontal circumference was noted. External examination showed a fused left eyelid which resulted in crytophthalmos. Both orbital cavities were severely hypoplastic, surrounded by oculo- motor muscles and abundant glial tissue. An optic remnant with retinal epithelium was bilaterally detected. Examination of the brain revealed a major dilatation of the lateral and third ventricles with hypoplastic white matter and optic nerve agenesis. Corpus callosum was absent and there was a minor hypoplasia of the inferior cerebellar vermis. Histological examination of the brain was normal for the term. No other malformations were found. Because of the cryptophthalmos aspect of one eye, the diagnosis of Fraser syndrome was suspected and the possibility of autosomal recessive inheritance was explained to the parents. Despite the past medical history, no prenatal diagnosis was performed for Case 2. A female was delivered *Correspondence to: Laurence Faivre, M.D., Ph.D., Centre de Ge ´ne ´tique, Ho ˆpital d’Enfants, 10, Boulevard Mare ´chal Delattre de Tassigny, 21034 Dijon Cedex, France. E-mail: laurence.faivre@chu-dijon.fr DOI 10.1002/ajmg.a.31114