Presentation: Patient with monogenic diabetes: Testing family members
When an individual has been diagnosed with monogenic diabetes, genomic testing should be offered to their first-degree relatives. Genomic counselling is required prior to testing for any family members who are not known to have diabetes.
At a glance:
- The most common subtypes of monogenic diabetes follow an autosomal dominant inheritance pattern, meaning that first-degree relatives have a 50% chance of being affected.
- Family members who already have a diabetes diagnosis should be offered genomic testing for the diabetes-causing variant, as this will determine whether their diabetes has the same genetic cause.
- First-degree relatives not known to have diabetes could be offered pre-symptomatic testing for the diabetes-causing variant. This requires genomic counselling prior to testing, to enable the individual to decide whether to proceed.
- Alert! The testing of family members carries various implications, depending on the gene affected and the variant identified, so specialist advice should be sought from the Exeter Clinical Laboratory team.
Example clinical scenario
A 30-year-old man has been diagnosed with HNF1A maturity-onset diabetes of the young (MODY) following genomic testing, and is asking about testing for other family members. He has a mother and a sister who have diabetes, and two children and a brother who are not known to be affected.
Identifying those at risk of a genetic condition
- It is important to ascertain exactly how family members are related to the affected individual in order to confirm whether they may be at risk of having inherited the pathogenic variant.
- The most common types of monogenic diabetes generally follow an autosomal dominant form of inheritance, meaning that first-degree relatives will have a 50% chance of inheriting the familial variant, regardless of their gender.
What do you need to do?
- The patient’s mother and sister should be offered genomic testing, because a diagnosis of HNF1A diabetes could have an impact on their treatment and may have implications for the sister’s children. The patient’s own children and his brother could be offered pre-symptomatic testing, but they will need pre-testing genomic counselling and should therefore be referred to a specialist diabetes or clinical genetics team.
- Enquire about other family members, identifying who is already known to have diabetes and who may be at risk. Drawing a family history can help.
- Family members already known to have diabetes can be referred directly (or can self-refer) for genomic testing for the identified variant.
- Family members who are at a 50% risk of having inherited the same variant but are not currently known to have diabetes can be referred for genomic counselling. For adults, this could be conducted by a diabetes team with special interest or experience in monogenic diabetes; for children, this could be conducted by their local clinical genetics service (or genomic testing could be delayed until they are old enough to make the decision for themselves).
- Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.
Resources
For clinicians
- Diabetic Genes: Genetic test referral forms
- Diabetes Genes: Overview (predictive testing)
- National Genomics Education Programme: Taking and drawing a family history
References:
- Shepherd M, Hattersley AT, Sparkes AC. ‘Predictive genetic testing in diabetes: A case study of multiple perspectives’. Qualitative Health Research 2000: volume 10, issue 2, pages 242–259. DOI: 10.1177/104973200129118390
For patients
- Diabetes Genes: Information for family members
- Diabetes Genes: Information for people with diabetes