From Karyotyping to Array-CGH in Prenatal Diagnosis

Abstract

Conventional karyotyping detects chromosomal anomalies in up to 35% of pregnancies with fetal ultrasound anomalies, depending on the number and type of these anomalies. Extensive experience gained in the past decades has shown that prenatal karyotyping is a robust technique which can detect the majority of germline chromosomal anomalies. For most of these anomalies the phenotype is known. In postnatal diagnosis of patients with congenital anomalies and intellectual disability, array-CGH/SNP array has become the first-tier investigation. The higher abnormality detection yield and its amenability to automation renders array-CGH also suitable for prenatal diagnosis. As both findings of unclear significance and unexpected findings may be detected, studies on the outcome of array-CGH in prenatal diagnosis were initially performed retrospectively. Recently, prospective application of array-CGH in pregnancies with ultrasound anomalies, and to a lesser extent in pregnancies referred for other reasons, was studied. Array-CGH showed an increased diagnostic yield compared to karyotyping, varying from 1–5%, depending on the reason for referral. Knowledge of the spectrum of array-CGH anomalies detected in the prenatal setting will increase rapidly in the years to come, thus facilitating pre- and posttest counseling. Meanwhile, new techniques like non-invasive prenatal diagnosis are emerging and will claim their place. In this review, we summarize the outcome of studies on prenatal array-CGH, the clinical relevance of differences in detection rate and range as compared to standard karyotyping, and reflect on the future integration of new molecular techniques in the workflow of prenatal diagnosis.

Prenatal Diagnosis of Cystic Hygroma related to a Deletion of 16q24.1 with Haploinsufficiency of FOXF1 and FOXC2 Genes

“…The value of whole genomic analysis is the ability to identify new genetic deletion or duplication syndromes [14]. Identifying new associations is not possible with the utilization of an array designed to detect known genetic pathology.…”

The introduction of arrays in prenatal diagnosis: A special challenge

“…Noninvasive prenatal diagnosis (NIPD), based on cell-free fetal DNA in maternal serum, enables the detection of a selected set of diagnoses (i.e., common aneuploidies) with a high sensitivity and without risk for miscarriages Papageorgiou et al, 2011]. Thus, in the near future, it is imaginable that NIPD will replace all the current biochemical screening tests or be the first-tier test after biochemical screening indicates an increased risk for Down syndrome, while genome-wide array investigations will be used only for those cases with abnormal ultrasound results [Lichtenbelt et al, 2011].…”

A prenatal missed diagnosed case of submicroscopic chromosomal abnormalities by karyotyping: the clinical utility of array-based CGH in prenatal diagnostics

“…As prior studies indicated, conventional karyotyping only identify chromosomal anomalies in about 35% of pregnancies with fetal ultrasound abnormalities, depending on the types of these anomalies [3]. Molecular cytogenetic techniques such as fluorescent in situ hybridisation (FISH), quantitative fluorescent PCR (QF-PCR) and multiplex ligation-dependent probe amplification (MLPA) overcome some of those limitations and are used as adjuncts to conventional methods for detecting common chromosome numerical anomalies [1], but none of them provides a genome wide screening for unexpected imbalances [4].…”