A COMPREHENSIVE ASSESSMENT OF CO-OCCURRING BIRTH DEFECTS AMONG INFANTS WITH NON-SYNDROMIC ANOPHTHALMIA OR MICROPHTHALMIA

Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defect patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate.
This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two – through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases.
We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects.
Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defect registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.

患有无眼畸形（anophthalmia）或小眼球畸形（microphthalmia）的婴儿常合并其他出生缺陷。然而，目前针对这类儿童的出生缺陷模式研究甚少。此类研究或可识别全新的多发畸形综合征，为探索无眼/小眼球畸形的发病机制提供新思路，同时帮助临床医师判断是否需要开展进一步检查。

本研究纳入1999年至2014年由德克萨斯州出生缺陷登记处（Texas Birth Defects Registry）确认的无眼/小眼球畸形病例，且这些病例未经临床或染色体检查确诊为已知综合征。我们针对合并无眼/小眼球畸形的二联至五联出生缺陷组合计算校正观测-期望比，以评估此类组合的共发频率是否高于独立发生时的预期水平。本研究仅报告观测病例数≥5例的缺陷组合。

本研究共纳入653例符合入组标准的无眼/小眼球畸形病例（其中514例，占79%，合并其他出生缺陷），涉及111种出生缺陷组合，包括44种二联组合、61种三联组合、6种四联组合，未发现五联组合。校正观测-期望比最高的组合涉及中枢神经系统（central nervous system, CNS）缺陷、头颈部缺陷及面裂。此外，本研究还观察到多种合并心血管与肌肉骨骼系统缺陷的组合。

与既往研究结果一致，本研究发现大部分确诊无眼/小眼球畸形的儿童合并存在其他出生缺陷。其中部分缺陷可能属于无眼/小眼球畸形相关病变序列的一部分（如中枢神经系统缺陷），而其他组合则可能提示尚未被阐明的易感模式（如肌肉骨骼系统缺陷）。基于人群的出生缺陷登记库数据，或可加速发现此前未被表征的畸形综合征。