Anophthalmia-esophageal atresia syndrome caused by an SOX2 gene deletion in monozygotic twin brothers with markedly discordant phenotypes

• Published in: American journal of medical genetics. Part A Vol. 140A; no. 18; pp. 1899 - 1903
• Main Authors: Zenteno, Juan Carlos, Perez-Cano, Hector J., Aguinaga, Monica
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.09.2006; Wiley-Liss
• Subjects: anophthalmia; Anophthalmos - diagnosis; Anophthalmos - genetics; Biological and medical sciences; esophageal atresia; Esophageal Atresia - diagnosis; Esophageal Atresia - genetics; Esophagus; Gastroenterology. Liver. Pancreas. Abdomen; Gene Deletion; HMGB Proteins - genetics; Humans; Infant; Male; Malformations; Malformations of the eye; Medical sciences; monozygotic twins; Ophthalmology; Phenotype; SOX2; SOXB1 Transcription Factors; Syndrome; Transcription Factors - genetics; Twins, Monozygotic; Human; Esophageal disease; anophthalmia; monozygotic twins; Congenital disease; Syndrome; Anophthalmos; SOX2; Eye disease; Phenotype; Gene; Malformation; Esophageal atresia; Deletion; Digestive diseases; Genetics; Monozygotic twin
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31384

The clinical combination of anophthalmia/microphthalmia and esophageal atresia was first recognized in 1988 as a distinct variable multi‐system malformation syndrome and since then at least 17 cases of the disease have been described, all of them sporadic in occurrence. We report a heterozygous SOX2 gene mutation underlying the syndrome of anophthalmia/microphthalmia‐esophageal atresia and demonstrate that this entity can be associated to considerable clinical variability as shown by the discordant ocular phenotype observed in monozygotic twin brothers carrying an SOX2 deletion. This is the first report describing a strikingly discordant eye phenotype in monozygotic twins with the condition, with one of our patients being the first reported individual carrying an SOX2 lesion associated with unilateral eye defect. We discuss the probable sources for this remarkable phenotypic heterogeneity of the anophthalmia/microphthalmia syndrome in individuals with an identical genetic constitution. © 2006 Wiley‐Liss, Inc.