These findings suggest that deletion of VCX-A and NLGN4 can result in variable phenotypic features and that normal mental development can be achieved despite this deletion, emphasizing the importance of environmental factors and possible modifier genes.

CMA increased detection rates and had a shorter turnaround time; therefore, late amniocentesis may serve as an extremely helpful tool for detecting abnormalities or reassuring parents following late appearing abnormal sonographic findings. However, CMA may expose uncertain findings for which the couple should be pre-counselled. The procedure appears safe. This article is protected by copyright. All rights reserved.

OBJECTIVE: To examine the choices of women with both high-risk and low-risk pregnancies who are undergoing prenatal chromosomal microarray analysis in a clinical setting regarding three challenging types of findings: variants of uncertain clinical significance, susceptibility loci for neurodevelopmental disorders, and copy number variants associated with risks for adult-onset conditions. We assessed whether women's choices were associated with indications for testing or with one-on-one pretest genetic counseling. METHODS: In this cross-sectional study, medical records of women who underwent invasive prenatal chromosomal microarray analysis testing (N=1,070) at Hadassah Medical Center between June 2017 and February 2018 were examined for testing indications, choices regarding chromosomal microarray analysis findings, and type of pretest genetic counseling. Multivariable analyses to assess associations with testing indication and prior genetic counseling were carried out using logistic regression models. RESULTS: In total, 56% of women (n=593) chose to be informed of all three types of findings and 20% (n=218) chose not to be informed of any of the findings beyond high-penetrance childhood-onset pathogenic findings. Variants of uncertain clinical significance as a single choice was the least-selected finding (2.5%, n=27). Low-risk pregnancies (ie, those with normal biochemical screening and fetal ultrasound examinations) were associated with increased interest in receiving genetic information about adult-onset conditions (adjusted odds ratio [aOR] 1.7; 95% CI 1.18–2.33) and susceptibility loci (aOR 1.5; 95% CI 1.08–2.10). CONCLUSION: Women with both high-risk and low-risk pregnancies were generally more likely to choose to receive additional genetic information, albeit differences in preferences depend on testing indication and type of pretest counseling.

What are the novel findings of this work?We calculated the rate of clinically significant chromosomal microarray analysis (CMA) findings in low-risk pregnancies, i.e. pregnancies with normal ultrasound (US) at the time of genetic testing, and found that the rate was relatively high. In addition, we documented later-appearing abnormal US findings and pregnancy outcome in these cases. What are the clinical implications of this work?The findings of this study allow an in-depth understanding of the yield of CMA and the impact of CMA results in pregnancies with normal US at the time of genetic testing. This may affect policy regarding CMA for low-risk pregnancies as well as counseling for prospective parents regarding the test and its possible results.