Presymptomatic testing

Presymptomatic genomic testing is performed in individuals who are at risk of a genetic condition but who do not yet show any signs or symptoms. In order to conduct presymptomatic testing, it is necessary to identify the specific genetic variant(s) in the patient’s affected relative.

A presymptomatic genomic test may be offered to patients who have a close relative in whom a genetic condition with an inheritance pattern that puts the patient at risk has been confirmed.

Presymptomatic testing can only be offered when the causative genetic variant is considered to be pathogenic or likely pathogenic. If the variants are only likely pathogenic, it is sometimes beneficial to have a discussion with the patient prior to offering testing. Testing is not routinely offered for variants of uncertain significance or benign variants.

A presymptomatic genomic test will only look for the genetic variant(s) identified in the affected family member. It does not look for other variants in the same gene or variants in other genes associated with similar symptoms.

Current guidance recommends that children are not offered genomic testing for adult-onset conditions unless they show signs of being affected by that specific condition. Alternative causes of any symptoms should be thoroughly explored prior to consideration of testing, and co-ordination with the local clinical genetics service is highly recommended.

Any predominantly adult-onset condition can be considered for presymptomatic genomic testing. It is most frequently considered in conditions that cause cancer, cardiac symptoms and neurological symptoms, but is relevant to all adult-onset conditions. When it comes to childhood-onset conditions, presymptomatic testing may be considered if there are substantive management implications for the child, such as initiation of invasive screening or surgical options, which cannot wait until the child can make that decision for themselves.

Presymptomatic testing is different to carrier testing for an autosomal recessive or X-linked condition. Carriers have a single genetic variant associated with a particular condition but will not usually be expected to develop signs or symptoms of that condition (they may develop symptoms for some conditions, but those symptoms are often milder and of later onset).

Presymptomatic genomic testing is offered only through clinical genetics services (National Genomic Test Directory test indication R242).

If an unaffected individual presents to a service and there is no evidence of the condition being present in the family, it is recommended that they are not tested and are instead referred to clinical genetics for discussion. A presymptomatic test in this situation could include non-genomic tests such as biochemical testing, MRI scans or cardiac investigations, which may identify typical signs of the condition in an asymptomatic person.

Testing in unaffected people predicts that signs and symptoms of the condition will occur during that person’s lifetime, but most often does not predict age of onset, pattern or severity of symptoms.

Genomic counselling for patients undergoing a presymptomatic test is often planned over more than one appointment, in which more than one health professional (consultant or genetic counsellor) may be involved. Discussion aims to cover a number of issues, including:

• an understanding of the condition in the family;
• support structures, both existing and required, including support groups;
• implications for other close family members;
• mental health support;
• financial, insurance and career considerations;
• reproductive options, including prenatal and preimplantation genetic testing;
• plans for provision of results;
• management or screening required following a positive presymptomatic test result; and
• available research studies.

For clinicians

• Association of British Insurers: Code on genetic testing and insurance
• NHS England: National Genomic Test Directory
• Royal College of Physicians: Genetic testing in childhood: Guidance for clinical practice (PDF, 59 pages)

For patients

• Genetic Alliance UK: Predictive testing