Genetic Counselling and Testing

Introduction

Genetic counselling is the process of helping a person or family understand and adapt to the medical, psychological and familial implications of a genetic contribution to disease. It sits alongside, but is distinct from, genetic testing: counselling is a conversation, testing is a laboratory investigation, and good practice never lets the second happen without the first.¹

The defining principle is non-directiveness. The counsellor's role is to present information accurately and neutrally so that patients reach their own decisions, in contrast to standard clinical practice where a doctor may reasonably recommend a course of action. This matters enormously in reproductive genetics, where a directive approach risks pressuring patients towards or away from testing, prenatal diagnosis or a pregnancy decision that is properly theirs alone to make.

This article covers the counselling process, the main categories of genetic test and when each is chosen, and the ethical framework - consent, confidentiality within families, and testing children - that governs how they are used in the NHS Genomic Medicine Service.

The counselling process

A genetic counselling consultation is longer and more structured than a typical outpatient appointment, often 45-60 minutes, and usually needs more than one session for anything but straightforward carrier testing.

1. Take a three-generation family history (pedigree), including ages, causes of death, ethnicity and consanguinity, since these determine both the differential diagnosis and the pattern of inheritance
2. Establish or confirm the diagnosis in the family, ideally by obtaining a molecular result on an affected relative before testing anyone else - testing an unaffected person first, without a known familial variant, is far less informative
3. Explain the inheritance pattern and recurrence risk in terms the patient can act on, checking understanding rather than assuming it
4. Explore the patient's ideas, concerns and expectations - what they think a positive or negative result would mean for them, and what they would do differently as a result
5. Discuss the options available: testing now, testing later, cascade testing of relatives, reproductive options, or declining testing altogether, all of which are legitimate choices
6. Support the decision reached, and arrange appropriate follow-up, surveillance or onward referral

Categories of genetic test

The same laboratory technique can serve very different clinical purposes depending on who is being tested and why. It is the clinical context, more than the test itself, that defines the category.

Laboratory techniques

Choosing the right test depends on the resolution needed: whether the suspected abnormality is a whole extra chromosome, a small deletion, or a single base change.

Karyotype

Microscopic examination of chromosomes arrested in metaphase, arranged in pairs. Detects numerical abnormalities (aneuploidy, such as trisomy 21) and large structural rearrangements - translocations, inversions, large deletions or duplications - down to a resolution of roughly 5-10 megabases. It remains first-line for suspected aneuploidy, for investigating recurrent miscarriage in a couple, and for detecting balanced translocations, which smaller-scale tests can miss entirely.

FISH (fluorescence in situ hybridisation)

Uses a fluorescently labelled probe complementary to a specific DNA sequence to confirm or exclude a targeted, known abnormality quickly - for example confirming 22q11.2 deletion in suspected DiGeorge syndrome, or detecting the BCR-ABL1 fusion in chronic myeloid leukaemia. It is fast but only answers the specific question asked; it will not detect an unsuspected abnormality elsewhere in the genome.

Chromosomal microarray (CMA)

Detects copy number variants - submicroscopic deletions and duplications - across the whole genome at far higher resolution than karyotyping, though it cannot detect balanced rearrangements (which do not change copy number) or single-gene point mutations. CMA is now first-line investigation for unexplained global developmental delay, learning disability, autism spectrum disorder or multiple congenital anomalies, having replaced karyotype for this indication because it roughly doubles the diagnostic yield.³

Next-generation sequencing: panels, exomes and genomes

• Gene panels sequence a curated set of genes known to cause a defined phenotype (e.g. an inherited cardiac arrhythmia panel), giving a high diagnostic yield with a low chance of unexpected findings
• Whole exome sequencing (WES) sequences the protein-coding regions of all genes (about 1-2% of the genome), useful when the phenotype does not point to one obvious gene
• Whole genome sequencing (WGS) sequences essentially the entire genome, including non-coding regulatory regions, and is now offered through the NHS Genomic Medicine Service for specific rare disease and cancer indications
• Broader tests carry a real, quantifiable chance of an incidental (secondary) finding unrelated to the reason for testing - for example a pathogenic BRCA1 variant found while investigating an unrelated condition - which must be discussed and consented for, or explicitly opted out of, before the test is sent

Cascade testing

Once a pathogenic variant is identified in an index case (the proband), cascade testing offers testing sequentially to first-degree relatives, then their first-degree relatives in turn, working outwards through the family. It is efficient because a targeted test for one known familial variant is quicker and cheaper than a de novo diagnostic work-up, and it is how conditions such as familial hypercholesterolaemia and hereditary breast and ovarian cancer syndromes are identified in relatives who are otherwise asymptomatic.

Cascade testing depends on the proband agreeing to their result being used to inform relatives, and on relatives themselves choosing to be tested - neither can be compelled. In practice the proband is usually asked to inform relatives directly, with written information from the genetics team to pass on, and support offered if that conversation is difficult.

Ethical and legal issues

Consent

Genetic test results differ from most other investigations in two important ways: they can have predictive implications reaching decades into the future, and a result is inherently informative about blood relatives who have not consented to anything. Both points should be made explicit as part of consent, alongside the standard discussion of what the test can and cannot answer.

Confidentiality within families

The general rule is that a genetic result belongs to the person tested and cannot be disclosed to relatives without their consent, even where that information would materially benefit a relative's own health. Patients are strongly encouraged, and supported, to share relevant results with family members themselves. Breaching confidentiality to warn a relative directly is only justifiable in an exceptional case - a serious, actionable risk, where the patient has been asked and has refused, and after seeking senior and legal advice - mirroring the general GMC framework for breaching confidentiality in the public interest.⁴

Testing children

• Testing for a condition with childhood-onset features, or where a result would change childhood surveillance or management, is appropriate at the time it is clinically useful - for example predictive testing for familial adenomatous polyposis, which needs colonoscopic surveillance to begin in the teenage years
• Predictive testing for a purely adult-onset condition with no childhood intervention available, such as Huntington's disease or adult-onset BRCA-related cancer risk, is deferred until the individual is old enough to decide for themselves, preserving their right to an open future and to choose not to know
• Carrier testing for reproductive purposes (as opposed to personal health risk) is similarly deferred until the person can make their own reproductive decisions
• Exceptions exist where a result in the child would materially change the family's own reproductive planning, which should be discussed on a case-by-case basis with the genetics team

Insurance

Under the UK Code on Genetic Testing and Insurance, insurers must not ask about or use predictive genetic test results, with a narrow exception for Huntington's disease and life insurance above a defined sum assured, where disclosure of a confirmed result may be required. Diagnostic results (confirming an existing condition) can still be relevant to underwriting, as with any other diagnosis.⁵

Prenatal and reproductive genetic testing

These options are covered in detail in the article on antenatal genetic screening; in brief, once a familial variant is known, couples have several routes to avoid transmitting it or to gain information during pregnancy:

• Preimplantation genetic testing (PGT), combined with IVF, tests embryos for a specific familial variant before transfer, avoiding the need for a decision about an established pregnancy
• Chorionic villus sampling (around 11-14 weeks) and amniocentesis (from around 15 weeks) allow diagnostic testing of an established pregnancy, each carrying a small procedure-related miscarriage risk
• Non-invasive prenatal testing (NIPT), analysing cell-free fetal DNA in maternal blood, is a highly sensitive screening test for the common aneuploidies but is not diagnostic, and a high-risk result requires confirmation by invasive testing before any irreversible decision is made

Newborn screening

The newborn blood spot (heel-prick) screening programme, offered to every baby around day 5, is a population-level example of genetic and metabolic screening distinct from the individualised testing described above: it is offered universally, not targeted by family history, and aims to detect treatable conditions before irreversible harm occurs.

A screen-positive result is not a diagnosis. It defines a group at high enough risk to warrant urgent diagnostic testing and specialist referral, and parents should be counselled in exactly those terms - most infants with a positive screen for cystic fibrosis, for instance, turn out not to have the disease once sweat testing and genetic analysis are complete.

Psychological aspects and support

Receiving a genetic result, whether diagnostic or predictive, can affect far more than the individual tested: it reshapes how someone understands their own future health, their reproductive choices, and their place within a family that may now be divided into those who carry a variant and those who do not.

• Survivor guilt is well documented in relatives who test negative for a familial variant that affects siblings, alongside relief
• A positive predictive result for an untreatable adult-onset condition carries a genuine risk of depression and, particularly in Huntington's disease, suicidal ideation, which is why structured pre-test counselling and psychological assessment precede the test rather than following an unexpected result
• Couples receiving a prenatal diagnosis of a serious condition need time-pressured but unhurried counselling covering continuing the pregnancy with support arranged, or ending it, without the counsellor's own view influencing the discussion
• Family dynamics can be disrupted by a diagnosis that implicates a parent as the transmitting carrier, particularly in X-linked or imprinted conditions, and this is worth naming explicitly rather than leaving families to navigate alone
• Patient support groups and condition-specific charities are a valuable adjunct to clinical follow-up and should be signposted routinely, not only when a family specifically asks

Referral and service structure

In the NHS, clinical genetics services are organised through Genomic Medicine Service Alliances, working from a National Genomic Test Directory that specifies which conditions and presentations meet the eligibility criteria for funded testing, and which test type is appropriate for each.⁶ Many mainstream specialties - cardiology, oncology, renal medicine - now hold their own mainstreamed genomic testing pathways for common indications, referring on to clinical genetics for complex counselling, rare phenotypes, or results with major reproductive or family implications.