Early detection of bilateral cataracts in utero may represent a manifestation of severe congenital disease.

We observed bilateral cataracts on second trimester ultrasound, in two consecutive pregnancies, with no other structural defects detected. The parents were unrelated and had no family history for the disease. The first pregnancy was terminated in week 22. Copy number variation analysis revealed, in both the aborted fetus and the mother, a 495 kb duplication at 22q11.23 encompassing CRYBB3 and CRYBB2, and not present in variation databases. In the second pregnancy, lens hyperechogenicity was detected by ultrasound at week 13 and 4 days. The identical duplication at 22q11.23 was found in the fetus and considered as possibly pathogenic. At weeks 22 and 30, smaller orbit measurements were elucidated on ultrasound, raising concerns as to the underlying molecular genetic cause, necessitating further investigation. Whole-exome sequencing, using DNA of the first fetus, was performed shortly after the birth of a male child, and two truncating RAB3GAP1 mutations were detected: c.538G>T; p. (Glu180*) and c.943C>T; p. (Arg315*). Neither mutation has been previously reported to be disease-causing; however, evaluation in the context of previously published literature indicated their deleterious nature, implying a clinical diagnosis of Warburg micro syndrome or Martsolf syndrome. Sanger sequencing confirmed segregation of the two mutations within the family, consistent with autosomal recessive inheritance. The child born from the second pregnancy showed features typical of Warburg micro syndrome, with the exception of microcephaly, at age 31 months. © 2016 Wiley Periodicals, Inc.

Exponentially weighted moving average chart as a suitable tool for nuchal translucency quality review.

OBJECTIVES: This study aimed to design an exponentially weighted moving average (EWMA) chart for the quality review of nuchal translucency (NT) and to assess its performance compared with the methods currently in use: retrospective distribution-based methods and the cumulative sum (CUSUM) chart. METHODS: The EWMA model was designed for NT quality review using simulation. The NT measurements obtained during routine first-trimester screening in our centre over a two-and-a-half-year period were retrieved from the database. The NT distribution parameters, EWMA and CUSUM chart were established, and the methods were compared. RESULTS: On the basis of the results from the simulation, the optimal EWMA settings were established. A set of 9338 NT measurements obtained from nine sonographers was used to construct the EWMA and CUSUM charts and to calculate the distribution parameters. Distribution-based methods were unable to reveal the temporal periods of poor performance. The EWMA model agreed closely with the CUSUM but had the advantage promptly indicating when the process returned to an in-control state, thus extending its use to long-term prospective and retrospective quality assessments. CONCLUSIONS: The EWMA provides a universal, easy and efficient tool for NT quality review when the prompt and effective detection of suboptimal performance is desired.

SNP array and phenotype correlation shows that FLI1 deletion per se is not responsible for thrombocytopenia development in Jacobsen syndrome.

Jacobsen syndrome (JBS) is a rare chromosomal disorder caused by terminal deletion of the long arm of chromosome 11. We report on four prenatally diagnosed patients with JBS with variable prenatal and postnatal phenotypes and 11q deletions of varying sizes. Precise characterization of the deleted region in three patients was performed by SNP arrays. The severity of both the prenatal and postnatal phenotypes did not correlate with the size of the haploinsufficient region. Despite the large difference in the deletion size (nearly 6 Mb), both of the live-born patients had similar phenotypes corresponding to JBS. However, one of the most prominent features of JBS, thrombocytopenia, was only present in the live-born boy. The girl, who had a significantly longer deletion spanning all four genes suspected of being causative of JBS-related thrombocytopenia (FLI1, ETS1, NFRKB, and JAM3), did not manifest a platelet phenotype. Therefore, our findings do not support the traditional view of deletion size correlation in JBS or the causative role of FLI1, ETS1, NFRKB, and JAM3 deletion per se for the development of disease-related thrombocytopenia.

Real-time quality control of nuchal translucency measurements using the exponentially weighted moving average chart.

OBJECTIVE: The establishment of ongoing audits for first-trimester nuchal translucency (NT) measurements is of paramount importance. The exponentially weighted moving average (EWMA) chart has been published as an efficient tool for NT quality control with the advantages of being suitable for real-time long-term monitoring. This study aimed to assess the efficacy of real-time NT quality control using EWMA charts. MATERIALS AND METHODS: This was an ongoing prospective study conducted from January 2011 to December 2017 at the Centre for Fetal Medicine Gennet in Prague. The quality of NT measurements was assessed using the NT retrospective distribution parameters and EWMA charts, and the results were presented to the sonographers during collective meetings. RESULTS: Overall, 28,928 NT measurements obtained from six sonographers were eligible for the study. Looking at individual EWMA charts, we observed four main outcomes. First, there was a clear improvement in the performance of sonographers with initially poor performances. Second, the performance of sonographers with an initially satisfactory quality was maintained. Third, there was an observed deterioration of the performance without the audits. Last, the sonographers appreciated an unequivocal and straightforward graphical presentation of EWMA curves. CONCLUSION: EWMA proved to be an efficient and suitable tool for real-time monitoring of NT quality and led to an overall improvement of the sonographers' performance.