Álvarez-Nava Francisco, Crenshaw Melissa L, Bedei Ivonne, Soto Marisol, Maciel-Guerra Andréa T, Skakkebæk Anne
Facultad de Ciencias Biológicas, Universidad Central del Ecuador, Quito, Ecuador.
Instituto de Investigaciones Genéticas de la Universidad del Zulia, Maracaibo, Venezuela.
Am J Med Genet C Semin Med Genet. 2025 Jun 25:e32146. doi: 10.1002/ajmg.c.32146.
It is evident that Turner syndrome (TS) impacts almost all developmental stages of the fetal heart with congenital heart disease (CHD) being seen in 23%-50% of individuals. Although the spectrum of CHDs in TS is well-established, with left-sided lesions predominating, the influence of specific karyotypes on the prevalence and types of CHDs remains incompletely understood. The primary objective of this systematic review/meta-analysis was to quantitatively synthesize the existing evidence on the association between specific karyotypes in TS and the risk of various CHDs. A systematic literature search was conducted through December 2023 to identify studies reporting the prevalence of CHDs in relation to TS karyotype. The quality of the individual studies was assessed using the Joanna Briggs Institute critical appraisal tools for systematic reviews. The overall estimates were pooled using both fixed- and random-effects models. Sensitivity and subgroup analysis were performed. Twenty-five studies were included in the analysis. TS individuals with a 45,X karyotype showed a significantly higher likelihood of bicuspid aortic valve (BAV) (pooled OR, 3.14 [95% CI: 2.49-3.94]), aortic coarctation (CoA) (pooled OR, 4.16 [95% CI: 2.74-6.31]), and partial anomalous pulmonary venous return (PAPVR) (pooled OR, 4.86 [2.31-10.2]) compared with TS individuals with a non-45,X karyotype. In addition, TS individuals with a 45,X karyotype also showed a significantly higher likelihood of BAV (pooled OR, 2.72 [95% CI: 1.62-4.56]) when compared with TS individuals with 45,X/46,XX mosaicism. TS individuals with a 45,X karyotype showed a significantly higher risk of BAV (pooled OR, 2.13 [95% CI: 1.42-3.21]) and CoA (pooled OR, 4.52 [95% CI: 1.58-13.0]) when compared with TS individuals with an isochromosome Xq. A significantly higher likelihood of BAV was also found in 45,X compared to other karyotypes (e.g., 45,X/46,XY and TS karyotypes with ring X chromosome). Some heterogeneity was evident, but publication was low. This meta-analysis confirms a strong association between the 45,X karyotype and increased prevalence of BAV, CoA, and PAPVR in TS. While 45,X/46,XX mosaicism and karyotypes with an isochromosome Xq mitigate risk, the findings emphasize the need for large-scale studies to refine risk assessment and management strategies.
显然，特纳综合征（TS）几乎影响胎儿心脏的所有发育阶段，23%-50%的患者患有先天性心脏病（CHD）。虽然TS中CHD的谱系已明确，以左侧病变为主，但特定核型对CHD患病率和类型的影响仍未完全了解。本系统评价/荟萃分析的主要目的是定量综合现有证据，以探讨TS中特定核型与各种CHD风险之间的关联。通过检索截至2023年12月的文献，以确定报告CHD患病率与TS核型关系的研究。使用乔安娜·布里格斯研究所系统评价的批判性评估工具评估个体研究的质量。采用固定效应模型和随机效应模型进行总体估计。进行敏感性分析和亚组分析。分析纳入了25项研究。与非45,X核型的TS患者相比，45,X核型的TS患者患二叶式主动脉瓣（BAV）（合并OR，3.14[95%CI：2.49-3.94]）、主动脉缩窄（CoA）（合并OR，4.16[95%CI：2.74-6.31]）和部分肺静脉异位引流（PAPVR）（合并OR，4.86[2.31-10.2]）的可能性显著更高。此外，与45,X/46,XX嵌合型的TS患者相比，45,X核型的TS患者患BAV的可能性也显著更高（合并OR，2.72[95%CI：1.62-4.56]）。与具有Xq等臂染色体的TS患者相比，45,X核型的TS患者患BAV（合并OR，2.13[95%CI：1.42-3.21]）和CoA（合并OR，4.52[95%CI：1.58-13.0]）的风险显著更高。与其他核型（如45,X/46,XY和具有环状X染色体的TS核型）相比，45,X核型的患者患BAV的可能性也显著更高。存在一些异质性，但发表偏倚较低。本荟萃分析证实45,X核型与TS中BAV、CoA和PAPVR患病率增加之间存在密切关联。虽然45,X/46,XX嵌合型和具有Xq等臂染色体的核型可降低风险，但研究结果强调需要开展大规模研究以完善风险评估和管理策略。
