Recent reports using genome-scale germline sequencing of paediatric cancer cohorts not selected for genetic risk suggest at least 10 per cent of paediatric cancer patients have a germline mutation in known cancer predisposition genes (Pui et al. 2019; Zhang et al. 2015).

Genetic abnormalities predisposing to ALL are rare individually, but as a group they account for

a growing proportion of ALL cases. Recognising an underlying leukaemia predisposition syndrome is essential to the clinical management. It is also relevant to relatives, who might also be at risk of developing the disease or may be potential stem cell donors.

The features that suggest a genetic predisposition may include:

• family history of the same or related cancers
• bilateral multifocal or multiple cancers
• earlier age at diagnosis than sporadic tumours of the same type
• physical findings that suggest a predisposition syndrome
• specific tumour types or certain pathological subtypes of cancer (determined by tumour genetic tests) that frequently occur in genetic predisposition.

Paired tumour/germline sequencing should be considered in some patients with a family history or clinical findings that suggest a possible cancer predisposition syndrome.

Once a diagnosis is confirmed, a comprehensive family cancer history of at least three generations’ pedigree will help further identify patients and families with potential cancer predisposition or inherited syndromes.

Anyone diagnosed with cancer should have a detailed personal and family cancer history taken. Consult relevant guidelines  to determine if referral to a familial cancer service is appropriate.

A familial cancer service assessment can determine if genetic testing is appropriate. Genetic testing is likely to be offered when there is at least a 10 per cent chance of finding a causative ‘gene error’ (pathogenic gene variant; previously called a mutation). Usually testing begins with a variant search in a person who has had cancer (a diagnostic genetic test). If a pathogenic gene variant is identified, variant-specific testing is available to relatives to see if they have or have not inherited the familial gene variant (predictive genetic testing).

Medicare funds some genetic tests via a Medicare Benefits Schedule (MBS) item number but most are not. Depending on the personal and family history, the relevant state health system may fund public sector genetic testing.

Pre-test counselling and informed consent is required before any genetic testing. In some states the treating team can offer ‘mainstream’ diagnostic genetic testing, after which referral is made to a familial cancer service if a pathogenic gene variant is identified. The familial cancer service can provide risk management advice, facilitate family risk notification and arrange predictive genetic testing for the family.

Visit the eviQ websitefor information on testing, referral and risk management guidelines for a number of inherited cancer predisposition syndromes.

Visit the Centre for Genetics Education website  for basic information about cancer in a family.