Reproductive genetic screening for information: evolving paradigms?

Reproductive genetic screening has introduced the possibility for pregnant women to learn, during the pregnancy or sometimes earlier, about the likelihood of their baby being affected with certain genetic conditions. As medicine progresses, the options afforded by this early information have expanded. This has led to a shifting paradigm in prenatal screening, wherein the early knowledge is seen as useful not solely for its inherent value to the pregnant woman, but also as enabling an expansion of conditions whose identification may allow early intervention and clinical impact. This article discusses this paradigm against the backdrop of prenatal genetic screening that is available today.

Known unknowns: building an ethics of uncertainty into genomic medicine.

BACKGROUND: Genomic testing has reached the point where, technically at least, it can be cheaper to undertake panel-, exome- or whole genome testing than it is to sequence a single gene. An attribute of these approaches is that information gleaned will often have uncertain significance. In addition to the challenges this presents for pre-test counseling and informed consent, a further consideration emerges over how - ethically - we should conceive of and respond to this uncertainty. To date, the ethical aspects of uncertainty in genomics have remained under-explored. DISCUSSION: In this paper, we draft a conceptual and ethical response to the question of how to conceive of and respond to uncertainty in genomic medicine. After introducing the problem, we articulate a concept of 'genomic uncertainty'. Drawing on this, together with exemplar clinical cases and related empirical literature, we then critique the presumption that uncertainty is always problematic and something to be avoided, or eradicated. We conclude by outlining an 'ethics of genomic uncertainty'; describing how we might handle uncertainty in genomic medicine. This involves fostering resilience, welfare, autonomy and solidarity. CONCLUSIONS: Uncertainty will be an inherent aspect of clinical practice in genomics for some time to come. Genomic testing should not be offered with the explicit aim to reduce uncertainty. Rather, uncertainty should be appraised, adapted to and communicated about as part of the process of offering and providing genomic information.

Symmetrical enchondromatosis is associated with duplication of 12p11.23 to 12p11.22 including PTHLH.

We describe a patient with striking generalized symmetrical enchondromatosis of the tubular bones and a de novo duplication of chromosome 12p11.23 to 12p11.22. The PTHLH gene within this region encodes a ligand for PTHR1: mutations in the gene encoding this receptor are associated with some cases of Ollier disease, several skeletal dysplasias including Blomstrand, Eiken, and Jansen and down-regulation of PTHLH expression in brachydactyly type E. Our findings suggest that abnormal PTHLH-PTHR1 signaling may underly this unusual form of enchondromatosis and indicate that unlike most cases of Ollier disease it is dominantly inherited.

Childhood genetic testing for familial cancer: should adoption make a difference?

Professional guidelines and practice in clinical genetics generally counsel against predictive genetic testing in childhood. A genetic test should not be performed in a child who is too young to choose it for himself unless that test is diagnostic, will lead to an intervention to prevent illness, or enable screening. It is therefore generally considered unacceptable to test young children for adult-onset cancer syndromes. However, these guidelines are challenged when clinical genetics services receive requests from adoption agencies or pre-adoptive parents for predictive genetic tests in children being placed for adoption. Testing will foreclose a pre-adoptive child's future autonomous right to choose, yet those commissioning these tests argue that adoption should form a special case. In this paper, we argue that predictive genetic testing as part of a pre-adoptive 'work-up' should be discouraged when the same test would not generally be carried out in a child who is not being adopted. We present an argument based on a principle of consistency and question those claims that privilege the adoptive process, whilst acknowledging the array of uncertainties faced by pre-adoptive parents. We suggest that if pre-adoptive testing is considered, this should only take place after prospective adoptive parents have had the opportunity to meet the clinical genetics team and fully understand the implications of the testing process.