Eye development genes and known syndromes

• Published in: Molecular genetics and metabolism Vol. 104; no. 4; pp. 448 - 456
• Main Author: Slavotinek, Anne M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2011
• Subjects: Abnormalities, Multiple - genetics; Animals; Anophthalmia/Microphthalmia; Anophthalmia–Esophageal–Genital (AEG) syndrome; Anophthalmos - genetics; Eye - growth & development; Genes, Developmental; Genetic Association Studies; Humans; Microphthalmos - genetics; Mutation; OTX2; Phenotype; SOX2; Syndrome; SOX2; OTX2; Anophthalmia/Microphthalmia; Anophthalmia–Esophageal–Genital (AEG) syndrome
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2011.09.029

Anophthalmia and microphthalmia (A/M) are significant eye defects because they can have profound effects on visual acuity. A/M is associated with non-ocular abnormalities in an estimated 33–95% of cases and around 25% of patients have an underlying genetic syndrome that is diagnosable. Syndrome recognition is important for targeted molecular genetic testing, prognosis and for counseling regarding recurrence risks. This review provides clinical and molecular information for several of the commonest syndromes associated with A/M: Anophthalmia–Esophageal–Genital syndrome, caused by SOX2 mutations, Anophthalmia and pituitary abnormalities caused by OTX2 mutations, Matthew-Wood syndrome caused by STRA6 mutations, oculofaciocardiodental syndrome and Lenz microphthalmia caused by BCOR mutations, Microphthalmia Linear Skin pigmentation syndrome caused by HCCS mutations, Anophthalmia, pituitary abnormalities, polysyndactyly caused by BMP4 mutations and Waardenburg anophthalmia caused by mutations in SMOC1. In addition, we briefly discuss the ocular and extraocular phenotypes associated with several other important eye developmental genes, including GDF6, VSX2, RAX, SHH, SIX6 and PAX6. ► Carefully describing the phenotype can aid identification of the correct gene. ► Many of the genes that cause anophthalmia/microphthalmia interact. ► Predicting phenotypes caused by interacting genes is complicated. ► Mutations in causative genes can be non-penetrant or vary in expressivity. ► Modifier genes, epigenetic factors and environment can influence clinical features.