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

## TL;DR

Portuguese geneticists face challenges in managing low-penetrance CNVs, with inconsistent practices and ethical concerns requiring national guidelines and shared decision-making.

## Contribution

Highlights the lack of consensus and ethical guidelines for managing LP-CNVs among Portuguese clinical geneticists.

## Key findings

- There is no agreement on whether LP-CNVs should be disclosed by expert panels or individualized.
- Clinicians recognize the need for shared decision-making due to patient challenges in understanding genetic information.
- Variability in ethical perspectives on prenatal and preimplantation testing for LP-CNVs was observed.

## Abstract

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.

An online questionnaire was administered to Clinical Geneticists in Portugal regarding their management of LP-CNV and ethical issues were addressed.

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.

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.