Older mothers and increased impact of prenatal screening: stable livebirth prevalence of trisomy 21 in the Netherlands for the period 2000-2013.

In the Netherlands, there is no registry system regarding the livebirth prevalence of trisomy 21 (T21). In 2007, a national screening programme was introduced for all pregnant women, which may have changed the livebirth prevalence of T21. The aim of this study is to analyse trends in factors that influence livebirth prevalence of T21 and to estimate the livebirth prevalence of T21 for the period of 2000-2013.

What do people want to know about NIPT? Content analysis of questions emailed to national NIPT information websites.

What's already known about this topic? Several countries, including the Netherlands, have implemented non‐invasive prenatal testing (NIPT) in their national prenatal screening program. Access to relevant online health information is important as it increases informed decision making. What does this study add? Visitors of national NIPT websites mostly request more information about testing beyond the currently available NIPT: a broader range of disorders (such as monogenic disorders) and increasing target group eligibility (such as low‐risk or twin pregnancies).

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands.

Hearing impairment (HI) is genetically heterogeneous which hampers genetic counseling and molecular diagnosis. Testing of several single HI-related genes is laborious and expensive. In this study, we evaluate the diagnostic utility of whole-exome sequencing (WES) targeting a panel of HI-related genes.

RARS2 Mutations: Is Pontocerebellar Hypoplasia Type 6 a Mitochondrial Encephalopathy?

Mutations in the mitochondrial arginyl tRNA synthetase (RARS2) gene are associated with Pontocerebellar Hypoplasia type 6 (PCH6). Here we report two patients, compound heterozygous for RARS2 mutations, presenting with early onset epileptic encephalopathy and (progressive) atrophy of both supra- and infratentorial structures. Early pontocerebellar hypoplasia was virtually absent and respiratory chain (RC) defects could not be detected in muscle biopsies.

Population-Attributable Risk of Risk Factors for Recurrent Wheezing in Moderate Preterm Infants During the First Year of Life.

Background: Recurrent wheezing in young infants has a high prevalence, influences quality of life, and generates substantial health care costs. We previously showed that respiratory syncytial virus infection is an important mechanism of recurrent wheezing in moderate preterm infants. We aimed to provide population-attributable risks (PAR) of risk factors for recurrent wheezing during the first year of life in otherwise healthy moderate preterm infants.

Maternal Plasma DNA and RNA Sequencing for Prenatal Testing.

Cell-free DNA (cfDNA) testing has recently become indispensable in diagnostic testing and screening. In the prenatal setting, this type of testing is often called noninvasive prenatal testing (NIPT). With a number of techniques, using either next-generation sequencing or single nucleotide polymorphism-based approaches, fetal cfDNA in maternal plasma can be analyzed to screen for rhesus D genotype, common chromosomal aneuploidies, and increasingly for testing other conditions, including monogenic disorders.

Two cases of RIT1 associated Noonan syndrome: Further delineation of the clinical phenotype and review of the literature.

Mutations in RIT1, involved in the RAS-MAPK pathway, have recently been identified as a cause for Noonan syndrome. We present two patients with Noonan syndrome caused by a RIT1 mutation with novel phenotypic manifestations, severe bilateral lower limb lymphedema starting during puberty, and fetal hydrops resulting in intrauterine fetal death, respectively. Including our patients, a total of 52 patients have been reported with Noonan syndrome caused by a RIT1 mutation.

Changing to NIPT as a first-tier screening test and future perspectives: opinions of health professionals.

Objective: The aim of this study was to investigate health professionals' opinions toward offering noninvasive prenatal testing (NIPT) as first-tier screening test regardless of pregnant women's risk, and toward a potential broader range of disorders.

Methods: A questionnaire completed by obstetric health professionals (n = 240) after an in-service NIPT training in the West and North of the Netherlands.

Results: The majority (72%) of respondents favored replacing first-trimester combined test (FCT) by NIPT, although 43% preferred to maintain nuchal translucency measurement.

[Maternal uniparental disomy 14; differential diagnosis with Prader-Willi syndrome].

Background: Maternal uniparental disomy 14 is a rare genetic disorder in which both chromosomes 14 are maternally inherited. The disorder is characterised by neonatal hypotonia and feeding difficulties, intrauterine or later growth retardation, truncal obesity and precocious puberty. During the neonatal period its clinical phenotype shows great similarities with that of Prader-Willi syndrome.