Congenital optic disc pits (ODPs) are well-circumscribed depressions within the optic disc. Thought to arise from anomalous closure of the optic fissure during embryonic development, they are now considered to lie on a broader spectrum of congenital optic disc anomaly (CODA). An increasing number of reports describe clustering of these cases within families, suggesting that inherited genetic elements play a role in disease predisposition. Here, we highlight the clinical features of 2 sets of father-son pairs affected with ODPs and provide preliminary molecular genetic analysis. Subjects underwent complete ophthalmological examination and imaging. In addition, whole-exome sequencing was carried out following informed consent. The resulting datasets were examined for potentially causal genetic variants, both in genes already known to be linked to CODA as well as those likely to lie in the same or similar genetic pathways. In this instance, no unambiguously causal variants were identified. This case series highlights the familial inheritance of ODPs, adding to the existing body of literature supporting an underlying genetic cause for this rare clinical entity. The inclusion here of specific molecular findings raises the hope that the genetic pathophysiology underlying rare entities like ODPs might be clarified in the future by the addition of similarly molecular-documented reports.
Case Rep Ophthalmol 2021;12:603–610

中文翻译：

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2 对父子中的家族性视盘凹坑：临床特征和遗传分析

先天性视盘凹陷 (ODP) 是视盘内界限清楚的凹陷。被认为是由胚胎发育过程中视裂异常闭合引起的，现在被认为属于更广泛的先天性视盘异常 (CODA)。越来越多的报告描述了这些病例在家族内的聚集，表明遗传因素在疾病易感性中起作用。在这里，我们重点介绍了 2 对受 ODP 影响的父子对的临床特征，并提供了初步的分子遗传分析。受试者接受了完整的眼科检查和成像。此外，在知情同意后进行全外显子组测序。检查所得数据集是否存在潜在的因果遗传变异，已知与 CODA 相关的基因以及可能位于相同或相似遗传途径的基因。在这种情况下，没有确定明确的因果变异。这个案例系列强调了 ODP 的家族遗传，增加了支持这种罕见临床实体潜在遗传原因的现有文献。在这里包含特定的分子发现提出了希望，通过添加类似的分子记录报告，未来可能会澄清像 ODP 这样的罕见实体背后的遗传病理生理学。添加到现有文献中，支持这种罕见临床实体的潜在遗传原因。在这里包含特定的分子发现提出了希望，通过添加类似的分子记录报告，未来可能会澄清像 ODP 这样的罕见实体背后的遗传病理生理学。添加到现有文献中，支持这种罕见临床实体的潜在遗传原因。在这里包含特定的分子发现提出了希望，通过添加类似的分子记录报告，未来可能会澄清像 ODP 这样的罕见实体背后的遗传病理生理学。
Case Rep Ophthalmol 2021；12:603–610