Ethical issues in genomic diagnosis and cascade testing

The mark goes to the candidate who separates four conversations that parents, and sometimes clinicians, collapse into one. The first is diagnostic testing of a sick child, where the ethical balance favours testing because the result changes management now. The second is predictive or carrier testing of a healthy child, where the balance usually favours waiting, because the child gains nothing in childhood and loses the right to decide as an adult. The third is the secondary finding, an actionable variant unrelated to the reason for testing that is returned only if the family opted in. The fourth is cascade testing, the obligation and the mechanism for offering testing to at-risk relatives once a pathogenic variant is confirmed in the proband. The candidate who can name which of the four is on the table, and apply the right rule, will pass this topic. [1] [2]

Overview & Definition

Ethical issues in genomic diagnosis and cascade testing arise whenever sequencing a child produces information that affects more than one person, more than one point in time, or more than one health decision. A genomic result travels in three directions at once: it informs the child's own care today, it predicts disease in the future adult the child will become, and it implicates parents, siblings, and relatives who share the variant. Each direction carries its own ethical weight, and the clinician must weigh them explicitly rather than default to "test everything and report everything." [1] [3]

The 2015 ASHG and ACMG "Points to Consider" statement, led by Botkin, is the current consensus framework for paediatric genetic testing. It updates the original 1995 ASHG/ACMG document and sits alongside the joint AAP and ACMG policy statement and technical report from 2013. Together these documents establish that parents may consent to testing that benefits the child, but that they should generally defer testing whose only value is adult — whether that is knowing one will develop an adult-onset disease, or knowing one is a carrier for a recessive condition. The guiding concept is the child's right to an open future: keep the child's options open until the child can make the decision personally. [1] [2]

Cascade testing is the structured process of offering testing to at-risk relatives once a pathogenic variant is confirmed in the proband. It is one of the highest-value interventions in clinical genetics, because identifying an affected or carrier relative before symptoms appear can enable surveillance, prevention, or reproductive planning. But cascade testing collides with confidentiality — the proband's identity cannot be shared with relatives without consent — and with the right not to know, because some relatives do not wish to learn their status. The clinician's job is to offer cascade testing, document the proband's consent, and respect each relative's choice. [3] [4]