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Trisomy 21 (Down syndrome) is the most common autosomal aneuploidy among newborns. About 90% result from meiotic nondisjunction during oogenesis, which occurs around conception, when also the most profound epigenetic modifications take place. Thus, maternal meiosis is an error prone process with an extreme sensitivity to endogenous factors, as exemplified by maternal age. This contrasts with the missing acceptance of causal exogenous factors. The proof of an environmental agent is a great challenge, both with respect to ascertainment bias, determination of time and dosage of exposure, as well as registration of the relevant individual health data affecting the birth prevalence. Based on a few exemplary epidemiological studies the feasibility of trisomy 21 monitoring is illustrated. In the nearer future the methodical premises will be clearly improved, both due to the establishment of electronic health registers and to the introduction of non-invasive prenatal tests. Down syndrome is a sentinel phenotype, presumably also with regard to other congenital anomalies. Thus, monitoring of trisomy 21 offers new chances for risk avoidance and preventive measures, but also for basic research concerning identification of relevant genomic variants involved in chromosomal nondisjunction. [ABSTRACT FROM AUTHOR]

Background: Karyotyping is considered the gold standard for the genome-wide detection of genomic imbalances in prenatal diagnosis, but it has a number of inherent limitations, namely the time required to culture cell and the limited resolution(5 ~ 10 Mb). Although fluorescence in situ hybridization (FISH) can also be used as a rapid prenatal diagnosis for common aneuploidies, it is labor intensive, requires prior knowledge of the regions of interest, and can only be used to diagnose one or a few genomic regions simultaneously. Array comparative genomic hybridization (aCGH) can overcome the resolution, the locus-specific, and the time limitations of the karyotyping and FISH techniques and is currently the most powerful method for detecting chromosomal alterations in pre and postnatal clinical cases. Several investigations have suggested that the aCGH testing should be considered a firsttier test for the diagnosis of cytogenetic aberrations in the fetus. Results: This study used karyotyping, FISH, sequence-tagged site (STS) analysis and aCGH to diagnose a case of de novo duplication of chromosome 21q22.12-q22.3 with other concomitant deletion and duplication of small fragments in 21q associated with Down syndrome prenatally. Conclusions: FISH, aCGH and STS analysis are useful in prenatal investigation of the nature of de novo alterations of small fragments of the chromosome. [ABSTRACT FROM AUTHOR]

Introduction: Non-Invasive Prenatal Testing (NIPT) for fetal aneuploidies using cell-free DNA (cfDNA) has been widely adopted in clinical practice due to its improved accuracy. A number of NIPT tests have been developed and validated. The purpose of this study is to evaluate the performance of the Veracity NIPT test for sex chromosome aneuploidy (SCA) detection in singleton pregnancies, autosomal aneuploidy detection in twin pregnancies and evaluation of Veracity clinical performance under routine NIPT conditions in a diverse cohort. Methods: Blinded retrospective study in singleton pregnancies (n = 305); blinded retrospective and prospective study in twin pregnancies (n = 306) and prospective evaluation of clinical performance in singleton and twin pregnancies (n = 10564). Results: Validation study results for the detection of SCAs in singleton pregnancies exhibited 100% sensitivity and specificity and correctly classified 7 (45,X), 4 (47,XXY), 2 (47,XXX) and 1 (47,XYY) cases. Validation study results for autosomal aneuploidy detection in twin pregnancies exhibited 100% sensitivity and specificity and correctly classified 3 trisomy 21, 1 trisomy 18 and 1 trisomy 13 samples. Clinical performance evaluation of Veracity was performed in 10564 pregnancies with median gestational age of 13 weeks, median maternal age 35 years and median gestational weight of 64 kg. Based on confirmation feedback the PPV for trisomies 21, 18 and 13 was estimated at 100% (95% CI, 92–100%), 100% (95% CI, 69–100%) and 71% (95% CI, 29–96%), respectively. Estimated PPV for Monosomy X was 57% (95%CI, 18–90%), while the NPV for SCA detection was estimated at 100% (95% CI, 99.94–100%). Conclusion: Veracity NIPT test is based on a very powerful, highly accurate methodology that can be safely applied in the clinical setting. [ABSTRACT FROM AUTHOR]