Navigating family dynamics and ethical considerations in genetic diagnosis of pulmonary arterial hypertension: insights from in-depth semi-structured interviews

Abstract

Background: Genetic diagnosis and precision medicine are rapidly advancing, driven by innovations in next-generation sequencing and omic methods. The UK's collaboration between national research initiatives and the National Health Service facilitates translation of research into clinical practice. This rapid transition impacts family dynamics and family planning, and raises ethical concerns, compounded by limited public and practitioner awareness of the long-term consequences of genetic diagnosis. Our objective is to explore the impact of genetic diagnosis on family dynamics and the ethical considerations of genetic testing at different life stages in patients with pulmonary arterial hypertension (PAH) and their at-risk relatives.

Methods: Stakeholders from the National Institute for Health Research BioResource Rare Diseases Study and the National Cohort Study of Idiopathic and Heritable Pulmonary Arterial Hypertension were recruited using purposive sampling. 53 interviews and focus groups with 63 participants were recorded, transcribed and thematically analysed using MAXQDA data analysis software.

Results: The study revealed three main themes: the impact of diagnosis on family dynamics, considerations for family planning, and genetic testing of relatives. Two attitudes toward testing offspring emerged: proactive advocates and gatekeepers. The gatekeeper stance was driven by three key factors: shielding children from genetic risk awareness, feelings of guilt or a desire to avoid blame for disease transmission, and limited family connections. Each theme highlighted various moral and ethical dilemmas faced by individuals.

Conclusions: A PAH diagnosis reshapes family roles and responsibilities. Genetic risk awareness strengthens bonds but also introduces challenges such as disclosing information and deciding on testing for at-risk relatives. Our research highlights the need for comprehensive genetic counselling and support systems to enhance patient care and familial wellbeing.

FIGURE 1

CONSORT (Consolidated Standards of Reporting Trials) flow diagram of RAPID-PAH. NIHR: National Institute for Health Research; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension. Reproduced with amendment, from [2, 8] with permission.

FIGURE 2

Insights into family life amidst the diagnosis. Three primary themes surfaced, encompassing the consequences of the diagnosis on family dynamics, the considerations related to family planning, and the genetic testing of relatives. Each of these themes revealed various moral and ethical dilemmas that individuals encountered.

FIGURE 3

Attitudes toward genetic research and testing: altruism, advocacy and gatekeeping perspectives. Most patients engaged in genetic research due to altruistic motives. Among those with mutations in pulmonary arterial hypertension risk genes, two distinct attitudes toward testing offspring emerged: proactive advocates and gatekeepers. The gatekeeper perspective stemmed from three primary factors: a responsibility to protect children from the weight of genetic risk awareness, feelings of guilt or a desire to evade blame for disease transmission, and the influence of limited family connections on the decision to involve relatives in testing. The width of the arrow reflects the weight of the theme, with thicker arrows signifying a stronger and more prevalent sentiment.