Estimates of live birth prevalence of children with Down syndrome in the period 1991-2015 in the Netherlands.

BACKGROUND: In Western countries, increasing maternal age has led to more pregnancies with a child with Down syndrome (DS). However, prenatal screening programs, diagnostic testing and termination of pregnancy influence the actual DS live birth (LB) prevalence as well. The aim of this study is to examine these factors in the Netherlands for the period 1991-2015. In our study, we establish a baseline for DS LB prevalence before non-invasive prenatal testing will be made available to all pregnant women in the Netherlands in 2017. METHODS: Full nationwide data from the Dutch cytogenetic laboratories were used to evaluate the actual DS LB prevalence. In addition, nonselective DS prevalence, which is the DS LB prevalence that would be expected in absence of termination of pregnancies, was estimated on the basis of maternal age distribution in the general population. RESULTS: Because of an increase in maternal age, nonselective DS prevalence increased from around 15.6 [95% confidence interval (CI) 13.9-17.4] per 10 000 LBs in 1991 (311 children in total) to around 22.6 (95% CI 20.3-24.9) per 10 000 in 2015 (385), the increase levelling off in recent years. Actual LB prevalence rose from around 11.6 (95% CI 10.9-12.2) per 10 000 in 1991 (230 children) to an estimated peak of 15.9 (95% CI 15.6-16.2) per 10 000 in 2002 (322), gradually decreasing since to 11.1 (95% CI 10.8-11.5) per 10 000 in 2015 (190). Reduction of DS LBs resulting from elective terminations had been fairly constant between 1995 and 2002 at around 28% and rose afterwards from 35% in 2003 to around 50% in 2015. CONCLUSIONS: In spite of expansion of antenatal screening in the Netherlands in the 1990s and early 2000s, actual DS LB prevalence increased during this period. However, after 2002, this trend reversed, probably because of informing all pregnant women about prenatal testing since 2004 and the implementation of a national screening program in 2007.

European non-invasive trisomy evaluation (EU-NITE) study: a multicenter prospective cohort study for non-invasive fetal trisomy 21 testing.

OBJECTIVE: To evaluate the performance of a directed non-invasive prenatal testing method of cell-free DNA analysis for fetal trisomy 21 (T21) by shipping the whole blood samples from Europe to a laboratory in the USA. METHODS: A European multicenter prospective, consecutive cohort study was performed enrolling pregnant women from Sweden and the Netherlands. Blood samples were drawn just prior to a planned of invasive diagnostic procedure in a population at increased risk for fetal T21 and then shipped to the USA without any blood processing. Chromosome-selective sequencing was carried out on chromosome 21 with reporting high risk or low risk of T21. Karyotyping or rapid aneuploidy detection was used as the clinical reference standard. RESULTS: Of the 520 eligible study subjects, a T21 test result was obtained in 504/520 (96.9%). Risk assessment was accurate in 503/504 subjects (99.8%). There was one false negative result for T21 (sensitivity 17/18, 94.4%, and specificity 100%). CONCLUSION: This is the first prospective European multicenter study showing that non-invasive prenatal testing using directed sequencing of cell-free DNA applied to blood samples shipped across the Atlantic Ocean, is highly accurate for assessing risk of fetal T21.

A 6Mb deletion in band 2q22 due to a complex chromosome rearrangement associated with severe psychomotor retardation, microcephaly and distinctive dysmorphic facial features.

High-resolution analyses of complex chromosome rearrangements (CCR) have demonstrated in individuals with abnormal phenotypes that not all seemingly balanced CCRs based on G-banding are completely balanced at breakpoint level. Here we report on an apparently balanced de novo CCR involving chromosomes 2, 3 and 5 present in a 6-month-old girl. She was referred for genetic evaluation because of severe psychomotor retardation, distinctive dysmorphic features and microcephaly. A 1Mb resolution array-CGH analysis of DNA from the patient revealed a deletion of about 6Mb for chromosome 2. FISH analysis showed that the deletion interval found in band 2q22 mapped at the translocation breakpoint, and that the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrome, is located within the deletion interval. To our knowledge this is the first case of a complex chromosomal rearrangement associated with Mowat-Wilson syndrome. Our data illustrate the important role for high-resolution investigation of apparently balanced chromosome rearrangements in patients with unexplained psychomotor retardation and/or other clinical features, and should contribute to our understanding of the mechanisms involved in chromosome rearrangement.