Sydney Ultrasound for Women, Sydney, Australia.
Faculty of Medicine, University of New South Wales, Sydney, Australia.
Prenat Diagn. 2017 Dec;37(13):1298-1304. doi: 10.1002/pd.5184.
The objectives of this study were to characterise genotype-phenotype discordance identified in the routine clinical setting and to explore the associated diagnostic and counselling challenges.
Cases were derived from a cohort of pregnant women who attended a multisite specialist prenatal screening and ultrasound service for non-invasive prenatal testing by cell-free DNA analysis and midtrimester fetal morphology assessment.
Seven cases of genotype-phenotype discordance were identified from a cohort of 12 919 women between June 2013 and March 2017 (incidence 1/1845 pregnancies). A variety of disorders of sexual differentiation were subsequently diagnosed.
Sex chromosomes are the basis of sexual differentiation during embryonic development. Variations of the traditional XX or XY karyotype may result in conditions where the genotype is discordant with the phenotype. Detection of these conditions in the past typically occurred during adolescence, due to delayed puberty, or during adulthood, due to infertility. With the increasing availability of non-invasive prenatal testing and high-resolution ultrasound, more cases of genotype-phenotype sex discordance are being identified in routine clinical practice during early pregnancy. These discordant results present significant diagnostic and counselling challenges, and their potential should be included in increasingly complex pre-NIPT counselling.
本研究旨在描述在常规临床环境中发现的基因型-表型不一致，并探讨相关的诊断和咨询挑战。
病例来源于一个孕妇队列，这些孕妇在进行非侵入性产前检测（通过游离 DNA 分析和中期胎儿形态评估）的多地点专科产前筛查和超声服务中接受检查。
在 2013 年 6 月至 2017 年 3 月期间，对 12919 名妇女的队列中发现了 7 例基因型-表型不一致的病例（发生率为 1/1845 妊娠）。随后诊断出多种性分化障碍。
性染色体是胚胎发育过程中性分化的基础。传统的 XX 或 XY 核型的变异可能导致基因型与表型不一致。过去这些情况的检测通常发生在青春期，由于青春期延迟，或在成年期，由于不孕。随着非侵入性产前检测和高分辨率超声的日益普及，在早期妊娠的常规临床实践中越来越多地发现基因型-表型性别不一致的病例。这些不一致的结果带来了重大的诊断和咨询挑战，应将其潜在风险纳入日益复杂的产前非侵入性检测咨询中。
