Ethical and clinical challenges in managing low-penetrance CNVs: insights from Portuguese clinical geneticists

低外显率拷贝数变异管理中的伦理和临床挑战:来自葡萄牙临床遗传学家的见解

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Abstract

INTRODUCTION: Low-Penetrance Copy Number Variants (LP-CNVs) are well-known to contribute to neurodevelopmental disorders and are also found in healthy individuals, presenting significant challenges to genetic counselling. However, data on the clinical management of LP-CNVs in Portugal is lacking. METHODS: An online questionnaire was administered to Clinical Geneticists in Portugal regarding their management of LP-CNV and ethical issues were addressed. RESULTS: The results showed a significant absence of agreement on LP-CNVs disclosure, particularly concerning whether decisions should be guided by expert panels or individualized for each case. Clinicians acknowledged the substantial challenges patients and families face in understanding genetic information, highlighting the need for a shared decision-making approach. Furthermore, there was considerable variability in ethical perspectives regarding prenatal diagnosis and preimplantation genetic testing for LP-CNVs, emphasizing the need for clear guidelines. Our results strongly advocate for the development of national guidelines mirroring those established in other countries. DISCUSSION: This work underscores several complex ethical issues requiring urgent exploration internationally. The observed postcode lottery highlights a failure of distributive justice, necessitating equitable access to standardized genomic knowledge across healthcare regions. Furthermore, the uncertainty challenge renders traditional non-directive counseling increasingly unsustainable, requiring a shift toward Shared Decision-Making (SDM) to balance child welfare against parental autonomy in navigating genomic ambiguity.

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