Anticipated stigma and blameless guilt: mothers' evaluation of life with the sex-linked disorder, hypohidrotic ectodermal dysplasia (XHED)

Practical experience of a genetic disorder may influence how parents approach reproduction, if they know their child may be affected by an inherited condition. One important aspect of this practical experience is the stigmatisation which family members may experience or witness. We outline the concept of stigma and how it affects those in families with a condition that impacts upon physical appearance. We then consider the accounts given by females in families affected by the rare sex-linked disorder, X-linked hypohidrotic ectodermal dysplasia (XHED), which principally affects males but can be passed through female carriers to affect their sons. The stigmatisation of affected males is as important in the accounts given by their womenfolk as the physical effects of the condition; this impacts on their talk about transmission of the disorder to the next generation. Perspectives may also change over time. The mothers of affected sons differ from their daughters, who do not yet have children, and from their mothers, who may express more strongly their sense of guilt at having transmitted the condition, despite there being no question of moral culpability. We conclude with suggestions about other contexts where the possibility of stigma may influence reproductive decisions

Musings on genome medicine: the value of family history

Will the routine availability of genome sequence information on individuals render family history information obsolete? I argue that it will not, both because the taking of a family history has other uses for the health professional, and because genome sequence data on their own omit the effects of numerous factors important for modifying risks of disease. These include information derived from factors downstream of genetic variants and from upstream epigenetic effects. Further difficulties arise with uncertainties relating to gene-gene and gene-environment interactions, which may take decades to resolve if their resolution is even possible

The challenge of consent in clinical genome-wide testing

Genome-wide testing methods include array comparative genomic hybridisation (aCGH), multiple gene panels, whole exome sequencing (WE) and whole genome sequencing (WGS). Here we introduce some of the key ethical and social considerations relating to informed consent for the testing of children, particularly the management of incidental findings and variants of unknown significance.</jats:p

Commentary on Eichinger J, Zimmermann B, Elger B, McLennan S, Filges I, Koné I. 2023. 'It's a nightmare': informed consent in paediatric genome-wide sequencing. A qualitative expert interview study from Germany and Switzerland.

This paper, reporting the views of medical genetics practitioners from Germany and Switzerland about the consent process for genome-based investigations of children, is timely. It shows the substantial challenges in clinical practice and, in particular, demonstrates the diversity of opinions among practitioners

The generation of an induced pluripotent stem cell line (DCGi001-A) from an individual with FOXG1 syndrome carrying the c.460dupG (p.Glu154fs) variation in the FOXG1 gene

FOXG1 syndrome is a neurodevelopmental disorder caused by mutations in the FOXG1 gene. Here, an induced pluripotent stem cell (iPSC) line was generated from human dermal fibroblasts of an individual with the c.490dupG (p.Glu154fs) mutation in the FOXG1 gene. Fibroblasts were reprogrammed using non-integrating episomal plasmids and pluripotency marker expression was confirmed by both immunocytochemistry and quantitative PCR in the resultant iPSC line. There were no karyotypic abnormalities and the cell line successfully differentiated into all three germ layers. This cell line may prove useful in the study of the pathogenic mechanisms that underpin FOXG1 syndrome

Discredited legacy: Stigma and familial amyloid polyneuropathy in Northwestern Portugal

Rationale Genetic inherited conditions may result in feelings of stigmatisation, mainly because of visible physical appearance and its transmissibility to offspring. Objective This article reports accounts of stigmatisation from Portuguese patients affected by the inherited neurodegenerative disease, familial amyloid polyneuropathy (FAP), living in the largest cluster of patients worldwide. Method We draw on semi-structured interviews conducted with individuals at-risk or affected by FAP, recruited through the national patients' association, about their experiences of stigmatisation related to the illness. Results Findings highlight the influence of a discrediting social context in the enactment of stigma. FAP was described as a source of devaluation and social distance and was permeated by beliefs of contagion in the community, especially in the past. The multigenerational nature of the illness within small communities was felt as a source of rejection for courtship and of devalued reproductive worth. Decisions to have (potentially affected) children seemed to be a target of implicit negative judgment. Dealing with stigma entailed restraint in talking about FAP especially outside the family, resistance to being treated as different, and social withdrawal. Some participants referred to recent substantial improvements in their social acceptance and a reduction in the intensity of the stigmatisation to which they are subject. Conclusion The pattern of stigma may have changed considerably within the past few decades, as medical information about the disease became more widespread, as new medications have been introduced and as clinical trials of other potential treatments have been established. Our findings report the social consequences of stigma towards this disease group and may help to understand how stigma is experienced in other heritable diseases

For your interest?:The ethical acceptability of using non-invasive prenatal testing to test 'purely for information'

Non-invasive prenatal testing (NIPT) is an emerging form of prenatal genetic testing that provides information about the genetic constitution of a foetus without the risk of pregnancy loss as a direct result of the test procedure. As with other prenatal tests, NIPT can help to make a decision about termination of pregnancy, plan contingencies for birth or prepare to raise a child with a genetic condition. NIPT can also be used by women and couples to test purely ‘for information’. Here, no particular action is envisaged following the test; it is instead entirely motivated by an interest in the result. The fact that NIPT can be performed without posing a risk to the pregnancy could give rise to an increase in such requests. In this paper, we examine the ethical aspects of using NIPT ‘purely for information,’ including the competing interests of the prospective parents and the future child, and the acceptability of testing for ‘frivolous’ reasons. Drawing on several clinical scenarios, we claim that arguments about testing children for genetic conditions are relevant to this debate. In addition, we raise ethical concerns over the potential for objectification of the child. We conclude that, in most cases, using NIPT to test for adult-onset conditions, carrier status or non-serious traits presenting in childhood would be unacceptable

Briefing: UK Ministry of Defence Force Protection Engineering Programme

The Defence Science and Technology Laboratory sponsored, QinetiQ-led Force Protection Engineering Research Programme has two main strands, applied and underpinning research. The underpinning strand is led by Blastech Ltd. One focus of this research is into the response of geomaterials to threat loading. The programme on locally won fill is split into four main characterisation strands: high-stress (GPa) static pressure–volume; medium-rate pressure–volume (split Hopkinson bar); high-rate (flyer plate) pressure–volume; and unifying modelling research at the University of Sheffield, which has focused on developing a high-quality dataset for locally won fill in low and medium strain rates. With the test apparatus at Sheffield well-controlled tests can be conducted at both high strain rate and pseudo-static rates up to stress levels of 1 GPa. The University of Cambridge has focused on using one-dimensional shock experiments to examine high-rate pressure–volume relationships. Both establishments are examining the effect of moisture content and starting density on emergent rate effects. Blastech Ltd has been undertaking carefully controlled fragment impact experiments, within the dataspace developed by the Universities of Sheffield and Cambridge. The data from experiments are unified by the QinetiQ-led modelling team, to predict material behaviour and to derive a scalable locally won fill model for use in any situation

Ethics experts and fetal patients: a proposal for modesty

Background Ethics consultation is recognized as an opportunity to share responsibility for difficult decisions in prenatal medicine, where moral intuitions are often unable to lead to a settled decision. It remains unclear, however, if the general standards of ethics consultation are applicable to the very particular setting of pregnancy. Main text We sought to analyze the special nature of disagreements, conflicts and value uncertainties in prenatal medicine as well as the ways in which an ethics consultation service (ECS) could possibly respond to them and illustrated our results with a case example. Ethics facilitation and conflict mediation, currently, have no broadly consented normative framework encompassing prenatal diagnosis and therapy as well as reproductive choice to draw on. Even so, they can still be helpful instruments for ethically challenging decision-making in prenatal medicine provided two additional rules are respected: For the time being, ECSs should (a) refrain from issuing content-heavy recommendations in prenatal medicine and (b) should not initiate conflict mediations that would involve the pregnant woman or couple as a conflict party. Conclusion It seems to be vital that ethics consultants as well as health care professionals acknowledge the current limitations and pitfalls of ethics consultation in prenatal medicine and together engage in the advancement of standards for this particularly complex setting