Pediatric Ophthalmology and Ocular Genetics, Flaum Eye Institute, University of Rochester, New York, New York, USA.
Department of Ophthalmology, University of Nigeria Teaching Hospital, Enugu, Nigeria.
Am J Med Genet A. 2023 Aug;191(8):2198-2203. doi: 10.1002/ajmg.a.63239. Epub 2023 May 10.
SOX2 pathogenic variants, though rare, constitute the most commonly known genetic cause of clinical anophthalmia and microphthalmia. However, patients without major ocular malformation, but with multi-system developmental disorders, have been reported, suggesting that the range of clinical phenotypes is broader than previously appreciated. We detail two patients with bilateral structurally normal eyes along with 11 other previously published patients. Our findings suggest that there is no obvious phenotypic or genotypic pattern that may help set apart patients with normal eyes. Our patients provide further evidence for broadening the phenotypic spectrum of SOX2 mutations and re-appraising the designation of SOX2 disorder as an anophthalmia/microphthalmia syndrome. We emphasize the importance of considering SOX2 pathogenic variants in the differential diagnoses of individuals with normal eyes, who may have varying combinations of features such as developmental delay, urogenital abnormalities, gastro-intestinal anomalies, pituitary dysfunction, midline structural anomalies, and complex movement disorders, seizures or other neurological issues.
SOX2 致病变体虽然罕见，但构成了临床无眼症和小眼症最常见的已知遗传原因。然而，已经报道了一些没有主要眼部畸形但有多系统发育障碍的患者，这表明临床表型的范围比以前认为的更广泛。我们详细介绍了两名双侧结构正常眼睛的患者以及其他 11 名先前发表的患者。我们的发现表明，没有明显的表型或基因型模式可以帮助区分正常眼睛的患者。我们的患者进一步证明了拓宽 SOX2 突变的表型谱，并重新评估将 SOX2 疾病指定为无眼症/小眼症综合征的合理性。我们强调在具有正常眼睛的个体的鉴别诊断中考虑 SOX2 致病变体的重要性，这些个体可能具有不同组合的特征，例如发育迟缓、泌尿生殖异常、胃肠道异常、垂体功能障碍、中线结构异常以及复杂运动障碍、癫痫发作或其他神经问题。
