Dilemmas in Prenatal Chromosomal Diagnosis Revealed Through a Single Center's 30 Years' Experience and 90,000 Cases

Abstract

Introduction: The aim of this article is to provide a perspective of prenatal chromosomal diagnosis (PCD) derived from a single center's evolving experience from ∼90,000 consecutive prenatal cases and to highlight important issues and current dilemmas. Materials and Methods: Prenatal cases in this study (1985-2013) were referred for various indications, and PCD was performed by standard karyotype in 84,255 cases, multiplex ligation-dependent probe amplification (MLPA) panel in 3,010 cases and standalone array comparative genomic hybridization (aCGH) in 3,122 cases. Results: Classic karyotype revealed 1.7 and 7.9% of pathological cases in amniotic fluid and CVS samples, respectively, with common aneuploidies accounting for 59.6 and 64.3% of the total abnormal. Molecular approaches increased the diagnostic yield by 0.6% for MLPA and 1.6% for aCGH, uncovering pathogenic chromosomal abnormalities undetectable by karyotype analysis. Conclusions: Current molecular diagnostic capabilities and the recent introduction of noninvasive prenatal testing (NIPT) point to one current major dilemma in PCD, with serious implications in genetic counseling, relating on the one hand to reaping the benefits from the high detection rate afforded through aCGH but accepting an invasive risk, and on the other hand, offering a lower detection rate practically only for Down syndrome, with minimal invasive risk.

Predicting fetoplacental chromosomal mosaicism during non‐invasive prenatal testing

“…The proportion of mosaicism for the common aneuploidies trisomy 21, 18, and 13 was 3.2% (5/154), 12.8% (5/39), and 13.3% (2/15), respectively (Table 2A). These numbers are slightly higher than previously reported by Konialis and Pangalos (2015). 30 In their large study of 73 268 fetal conventional karyotypes, trisomy 21, 18, and 13 mosaicism was detected in 2%, 4.8%, and 9.6%, respectively.…”

“…These numbers are slightly higher than previously reported by Konialis and Pangalos (2015). 30 In their large study of 73 268 fetal conventional karyotypes, trisomy 21, 18, and 13 mosaicism was detected in 2%, 4.8%, and 9.6%, respectively. The slightly higher numbers obtained with NIPT likely indicate that NIPT is more sensitive to detect placental mosaicism.…”

Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal aberrations: systematic review and meta‐analysis

“…The electronic search yielded 4252 articles, of which 36 were reviewed in full text. Several potentially relevant papers were excluded because they did not include patients with isolated AMA or ANX, the total number of AMA/ANX patients tested with microarray could not be retrieved, the referral groups were not described clearly (it was unclear whether the patients presented isolated AMA) or non‐homogeneous categories were used (e.g.…”

Balanced reciprocal translocation at amniocentesis: cytogenetic detection and implications for genetic counseling

“…These technologies are, however, limited to detecting the most common aneuploidies such as trisomies 13, 18, and 21, and do not detect balanced translocations (Wapner et al, 2012;Novelli et al, 2013;Konialis and Pangalos, 2015).…”