Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA.
Clinical Genetics Section, The Children's Hospital of San Antonio, San Antonio, TX, USA.
J Pediatr Urol. 2021 Feb;17(1):64.e1-64.e8. doi: 10.1016/j.jpurol.2020.11.015. Epub 2020 Nov 12.
Hypospadias, one of the most common male genital birth defects, occurs in 1 out of every 200 male births in the United States and is increasing in prevalence globally.
This study aimed to characterize the combinations of birth defects that co-occur with hypospadias more often than expected by chance, while accounting for the complex clustering patterns of congenital defects.
We analyzed cases with hypospadias and at least one additional co-occurring defect from the Texas Birth Defect Registry born between 1999 and 2014. For each combination, we calculated adjusted observed-to-expected (O/E) ratios, using Co-Occurring Defect Analysis (CODA).
Among 16,442 cases with hypospadias and without known syndromes, 2,084 (12.7%) had at least one additional defect. Many of the birth defect combinations within the highest adjusted O/E ratios included cardiac, musculoskeletal, and additional urogenital defects. For example, a top combination with an adjusted O/E of 139.0 included renal agenesis and dysgenesis, reduction defects of the upper limb, and other anomalies of upper limb (including shoulder girdle). High adjusted O/E ratios were also observed in combinations that included defects outside of the urogenital developmental field. For instance, the combination with the highest O/E ratio included buphthalmos, and congenital cataract and lens anomalies (adjusted O/E ratio: 192.9). Similar results were obtained when we restricted our analyses to cases with second- or third-degree hypospadias.
Many combinations in the top results were expected (e.g., multiple urogenital defects); however, some combinations with seemingly unrelated patterns of defects may suggest the presence of some etiologic mechanisms yet to be identified.
In summary, this study described patterns of co-occurring defect combinations with hypospadias that can inform further study and may provide insights for screening and diagnostic practices.
尿道下裂是美国最常见的男性生殖器出生缺陷之一，每 200 名男婴中就有 1 名患有尿道下裂，且其全球发病率呈上升趋势。
本研究旨在描述尿道下裂患者同时伴有多种其他出生缺陷的情况，同时考虑到先天性缺陷的复杂聚类模式。
我们分析了 1999 年至 2014 年间，德克萨斯州出生缺陷登记处登记的患有尿道下裂且至少伴有另一种并发缺陷的病例。对于每种组合，我们使用共现缺陷分析（CODA）计算了校正后的观察到的与预期的（O/E）比值。
在 16442 例无已知综合征的尿道下裂病例中，有 2084 例（12.7%）至少伴有一种其他缺陷。在最高校正 O/E 比值的许多出生缺陷组合中，包括心脏、肌肉骨骼和其他泌尿生殖系统缺陷。例如，一个最高校正 O/E 比值为 139.0 的组合，包括肾发育不全和发育不良、上肢减少缺陷以及上肢其他异常（包括肩带）。在包括泌尿生殖系统发育领域以外的缺陷的组合中，也观察到了较高的校正 O/E 比值。例如，O/E 比值最高的组合包括巨眼球和先天性白内障及晶状体异常（校正 O/E 比值：192.9）。当我们将分析限制在二级或三级尿道下裂病例时，得到了类似的结果。
许多最高结果中的组合是预期的（例如，多种泌尿生殖系统缺陷）；然而，一些看似无关的缺陷模式的组合可能表明存在一些尚未确定的病因机制。
总之，本研究描述了尿道下裂伴发其他缺陷组合的模式，可为进一步研究提供信息，并可能为筛查和诊断实践提供见解。
