Rare health conditions 54: arthrogryposis multiplex congenita, Edwards syndrome, and offering spiritual support

The purpose of this series is to highlight a range of rare health conditions. Rare health conditions are those that affect no more and usually fewer than 1 person in every 2000 and many HCAs and nurses will encounter some of these conditions, given the high number of them. This 54th article will examine two of these conditions, arthrogryposis multiplex congenita and Edwards syndrome, along with an exploration of the idea of support staff offering spiritual support to those with rare health conditions and their families.

Systematic evaluation of NIPT aneuploidy detection software tools with clinically validated NIPT samples

Non-invasive prenatal testing (NIPT) is a powerful screening method for fetal aneuploidy detection, relying on laboratory and computational analysis of cell-free DNA. Although several published computational NIPT analysis tools are available, no prior comprehensive, head-to-head accuracy comparison of the various tools has been published. Here, we compared the outcome accuracies obtained for clinically validated samples with five commonly used computational NIPT aneuploidy analysis tools (WisecondorX, NIPTeR, NIPTmer, RAPIDR, and GIPseq) across various sequencing depths (coverage) and fetal DNA fractions. The sample set included cases of fetal trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). We determined that all of the compared tools were considerably affected by lower sequencing depths, such that increasing proportions of undetected trisomy cases (false negatives) were observed as the sequencing depth decreased. We summarised our benchmarking results and highlighted the advantages and disadvantages of each computational NIPT software. To conclude, trisomy detection for lower coverage NIPT samples (e.g. 2.5M reads per sample) is technically possible but can, with some NIPT tools, produce troubling rates of inaccurate trisomy detection, especially in low-FF samples.

Next Generation Sequencing Based Non-invasive Prenatal Testing (NIPT): First Report From Saudi Arabia

Background: Non-invasive prenatal testing (NIPT) for aneuploidy in pregnant women screening has been recently established in Saudi Arabia. We aim from this study to report our experience in the implementation of this new technology in clinical practice and to assess factors influencing cell-free fetal (cffDNA) fraction and successful NIPT reporting.Methods: In total, 200 pregnant women were subjected to the NIPT test using standard methods. Next-generation sequencing (NGS) was used to analyze cffDNA in maternal plasma.Results: Out of the 200 NIPT cases, the average age of pregnant women was 35 ± 6 years (range: 21–48 years). The average cffDNA fraction of reported cases was 13.72% (range: 3–31%). Out of these 200 cases, 187 (93.5%) were at low risk, while 13 (6.5%) cases revealed high risk for aneuploidy. Among these chromosomal abnormalities, 7 (3.5%) cases of Down’s syndrome, 5 (2.5%) Edwards’ Syndrome, and only 1 case of (0.5%) Patau’s syndrome was observed. Out of the 13 high-risk cases, 2 (15.3%) were found in women below the age of 30.Conclusion: This is the first study reporting the successful implementation of an in-house NIPT screening service in Saudi Arabia. Our data showed high accuracy and sensitivity to detect high-risk cases indicating the usefulness of such a technique as an alternative to invasive testing and (hopefully) will change the common screening practice for pregnant women in Saudi Arabia.

Neurological findings of a series of patients with chromosome 18 trisomy (Edwards syndrome) in mosaic

Introduction: Chromosome 18 trisomy or Edwards syndrome (ED) is characterized by wide clinical manifestations, usually associated with neurological symptoms and a poor prognosis. Objective, materials and methods: Describe the clinical findings, especially the neurological ones, of a sample of patients with mosaic chromosome 18 trisomy. These were evaluated at a Clinical Genetics Service from 1975 to 2008. Results: During the study, 50 patients with ED were diagnosed, 5 of them (10%) in mosaic. The average number of cells analyzed in these cases was 27,8. Three of the 5 patients (60%) were male. The age at evaluation ranged from 14 to 5926 days (median 93 days). The small number of clinical findings described was noteworthy, both in the dysmorphological evaluation and complementary exams. The main changes were micrognathia (n = 3), low ears implanted (n = 2), retroverted ears (n = 3), clenched fists with overlapping toes (n = 2) and clubfoot (n = 1). As for internal organs, congenital heart disease was reported in 2 cases (40%). All patients had a history of delayed neuropsychomotor development. The older patient also had a description of cognitive impairment and seizures. Conclusions: The clinical presentation of our patients is consistent with what is described in the literature, since they point out due to small number of changes. However, the delay in neuropsychomotor development and neurological symptoms are constant findings. Thus, pediatricians and neurologists should be aware of this possibility.

A Dual Gender Rare Case with 47,XY, + 18/46,XX Karyotype: Chimera or Mosaic?

Our objective is to report one rare case of dual gender chimerism involving abnormal male trisomy 18 and normal female karyotype. The baby was born full term with birth weight of 1.8 kg, not vigorous with light meconium stained liquor and Apgar score of 51, 85 and 910. Parents are 40 years old and mother is G6P5 + 1. The baby had clinical features of Edwards syndrome, and a blood sample was sent to Human Genome Centre, Universiti Sains Malaysia, Malaysia for cytogenetic analysis. Conventional cytogenetic analysis results showed two distinct sex discordant genetic cell lines XY and XX in 90:10 ratio. The male genetic cell line XY also showed trisomy 18 (47,XY, + 18) consistent with clinical diagnosis of male Edwards syndrome, whereas the second genetic cell line showed normal 46,XX female. The present case was reported as dual gender chimera with chi 47,XY, + 18/46,XX karyotype pattern. To the best of available knowledge, dual gender chimerism with abnormal male trisomy 18 and normal female karyotype has not been reported so far, and this case is reported for its rarity and as the first report.