Table 1_Ethical and clinical challenges in managing low-penetrance CNVs: insights from Portuguese clinical geneticists.xlsx

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

引言 低外显率拷贝数变异（Low-Penetrance Copy Number Variants, LP-CNVs）是公认的神经发育障碍致病因素，同时也可在健康个体中检出，这给遗传咨询带来了显著挑战。然而，目前葡萄牙境内关于LP-CNVs临床管理的相关数据仍存在缺失。
方法 本研究针对葡萄牙临床遗传学家开展在线问卷调查，内容涵盖其对LP-CNVs的临床管理实践，并对相关伦理问题进行了探讨。
结果 研究结果显示，学界在LP-CNVs的信息披露问题上存在显著分歧，尤其是在决策应基于专家小组指导还是针对每个病例进行个体化制定这一议题上。临床医生指出，患者及其家庭在理解遗传信息时面临诸多困难，凸显了推行共同决策模式的必要性。此外，针对LP-CNVs的产前诊断与植入前基因检测，各方的伦理观点存在较大差异，这进一步强调了制定明确指南的迫切性。本研究结果强烈呼吁制定符合他国成熟标准的国家级临床指南。
讨论 本研究凸显了多项亟待全球范围内深入探讨的复杂伦理议题。本次调研中发现的区域医疗服务不均现象，凸显了分配正义的缺失，这要求各医疗区域能够公平获取标准化的基因组学知识。此外，信息不确定性的挑战使得传统非指导性咨询模式愈发难以为继，亟需转向共同决策（Shared Decision-Making, SDM）模式，以在应对基因组信息模糊性时，平衡儿童福祉与父母自主权之间的关系。