Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges—Systematic Review of the Literature and Meta-Analysis

Diagnostics

Antonio Pizzuti¹  Gioia Mastromoro¹  Alice Traversa¹  Nader Khaleghi Hashemian¹  Daniele Guadagnolo¹  Enrica Marchionni¹ 

[1] Department of Experimental Medicine, Policlinico Umberto I Hospital, Sapienza University of Rome, 00161 Rome, Italy;

关键词: molecular approaches;    chromosomal microarray;    exome sequencing;    genome sequencing;    prenatal diagnosis;    genetic counseling;   

DOI  :  10.3390/diagnostics12030575

来源: DOAJ

【 摘 要 】

Fetal malformations occur in 2–3% of pregnancies. They require invasive procedures for cytogenetics and molecular testing. “Structural anomalies” include non-transient anatomic alterations. “Soft markers” are often transient minor ultrasound findings. Anomalies not fitting these definitions are categorized as “dynamic”. This meta-analysis aims to evaluate the diagnostic yield and the rates of variants of uncertain significance (VUSs) in fetuses undergoing molecular testing (chromosomal microarray (CMA), exome sequencing (ES), genome sequencing (WGS)) due to ultrasound findings. The CMA diagnostic yield was 2.15% in single soft markers (vs. 0.79% baseline risk), 3.44% in multiple soft markers, 3.66% in single structural anomalies and 8.57% in multiple structural anomalies. Rates for specific subcategories vary significantly. ES showed a diagnostic rate of 19.47%, reaching 27.47% in multiple structural anomalies. WGS data did not allow meta-analysis. In fetal structural anomalies, CMA is a first-tier test, but should be integrated with karyotype and parental segregations. In this class of fetuses, ES presents a very high incremental yield, with a significant VUSs burden, so we encourage its use in selected cases. Soft markers present heterogeneous CMA results from each other, some of them with risks comparable to structural anomalies, and would benefit from molecular analysis. The diagnostic rate of multiple soft markers poses a solid indication to CMA.

【 授权许可】

Unknown