Dap Matthieu, Harter Hélène, Lambert Laetitia, Perdriolle-Galet Estelle, Bonnet Céline, Morel Olivier
Obstetrics and Fetal medicine Unit, CHRU of Nancy, Nancy, France.
Department of Fetopathology and Placental Pathology, CHRU of Nancy, Nancy, France.
J Matern Fetal Neonatal Med. 2022 Dec;35(26):10384-10387. doi: 10.1080/14767058.2022.2128654. Epub 2022 Sep 27.
To evaluate the contribution of genetic investigations in case of isolated bilateral clubfoot detected by routine prenatal ultrasound. Pathogenic Copy Number Variations is about 3.9% in fetuses with isolated clubfoot (uni- or bilateral). We hypothesize that this rate could be higher in a homogenous group of fetuses with bilateral clubfoot.
This retrospective single-center study included all women referred to our fetal-medicine center between 2013 and 2020 after ultrasound detection of isolated bilateral clubfoot. Genetic counseling was offered in which the woman was offered an amniocentesis for CMA and targeted investigation for Prader-Willi Syndrome (PWS), Steinert's disease and Spinal Muscular Atrophy (SMA).
34 women were referred, 18 of them consented to undergo genetic studies by amniocentesis (18/34; 52.9%). Pathogenic copy number variations (CNVs) were found in 2/18 (11.1%) of cases. One of these CNVs was directly linked to the clubfoot pathology (a deletion in 5q31.1 containing PITX1 gene). Four fetuses (4/18, 22.2%) had variants of unknown significance (VUS). No PWS, SMA or Steinert's disease was found. No case diagnosed with isolated clubfoot prenatally had additional anomalies postnatally.
In the case of bilateral isolated clubfoot detected at the antenatal ultrasound, invasive prenatal testing should be offered, and if accepted, a CMA should be done, as pathogenic variations were observed in up to 11.1% of women who got amniocentesis. The findings of this study do not support the systematic recommendation of molecular studies for PWS, SMA, Steinert's disease.
评估常规产前超声检测出孤立性双侧马蹄内翻足病例中基因检测的作用。孤立性马蹄内翻足（单侧或双侧）胎儿的致病性拷贝数变异率约为3.9%。我们推测，在一组均一的双侧马蹄内翻足胎儿中，这一比例可能更高。
这项回顾性单中心研究纳入了2013年至2020年间因超声检测出孤立性双侧马蹄内翻足而转诊至我们胎儿医学中心的所有孕妇。提供了遗传咨询，为孕妇提供羊膜腔穿刺术进行染色体微阵列分析（CMA）以及针对普拉德-威利综合征（PWS）、斯坦纳特病和脊髓性肌萎缩症（SMA）的靶向检测。
34名孕妇被转诊，其中18名同意通过羊膜腔穿刺术进行基因研究（18/34；52.9%）。在2/18（11.1%）的病例中发现了致病性拷贝数变异（CNV）。其中一个CNV与马蹄内翻足病理直接相关（5q31.1缺失，包含PITX1基因）。4例胎儿（4/18，22.2%）有意义未明的变异（VUS）。未发现PWS、SMA或斯坦纳特病。产前诊断为孤立性马蹄内翻足的病例出生后均无其他异常。
对于产前超声检测出的双侧孤立性马蹄内翻足病例，应提供侵入性产前检测，如果孕妇接受，应进行CMA，因为在接受羊膜腔穿刺术的女性中，高达11.1%观察到了致病性变异。本研究结果不支持对PWS、SMA、斯坦纳特病进行分子研究的系统性推荐。
