Familial infiltrative fibromatosis and issues of consent

1. Familial infiltrative fibromatosisandissues of consent

2. Familial infiltrative fibromatosis (FIF) • FIF = Hereditary Desmoid disease • Caused by mutations in APC gene (often 3’ end of gene, distal to the beta catenin binding domain) • Variant of FAP • Desmoid disease as well as FAP • Desmoid disease alone • Desmoid tumours are not neoplastic but are locally very invasive • Three types • Desmoid tumours that spontaneously regress (rare) • Patients with stable disease that does not regress • Patients with severe progressive disease that is fatal • Patients at risk of FAP or FIF undergo screening (genetic or bowel)

3. Bowel Screening • Called up at 10 - 14 years • Rigid sigmoidoscopy in out-patients • Around 16-20 years undergo colonoscopy with dye-spray • Colonoscopy clear • Rigid sigmoidoscopy in out patients yearly • Colonoscopy with dye-spray 5 yearly • Polyps found at colonoscopy • Confirmed to have FAP • Surgery and further screening discussed

4. Genetic screening • Predictive Genetic Test • Mutation identified in families • Called up age 10 - 14 years • Genetic Counseling • Results 2/52 (since the white paper) • Gene positive individuals entered into bowel screening program • Gene negative individuals • Still population risk of bowel cancer

5. Scenario (Early 2005) • 14 year female with a very strong family history (paternal) of FIF (mutation known) • Had previously undergone some bowel screening but had been lost from the system • Presented with bowel problems • Constipation and bleeding • As part of investigations for symptoms it was decided to: • Restart her bowel screening program • Test her for familial APC mutation to help eliminate desmoid disease • If negative bowel screening would not have to continue • Clinic date was arranged to give patient results in 6 weeks

6. One problem….. • Patient and her mother were estranged from the father and his family • Consent to use the fathers familial information to test the patient was REFUSED. • What do we do next ? • We know what mutation to test the patient for • To not test at all would mean that the patient may have to undergo bowel screening unnecessarily • Clinic date already arranged for 6 weeks time so time was short

7. Options • Screen the whole gene • If no mutation found this could be because the patient had not inherited the mutation OR the technique employed was not able to detect mutation • Whole gene screen was predicted to take over two months • Screen exon 15 of APC (mutation hotspot of APC) • Quicker but still the same issues if no mutation identified 1+2 would have been viable options if a mutation had been identified • Test for the familial mutation despite consent from the family being refused

8. What we did… • We contacted West Midlands Regional Genetics laboratory informed them of the situation • A sample was sent immediately to the lab • A whole gene screen was commenced • Issue raised in a meeting with all Clinical staff, problem discussed at length • No resolution • Eventually it was decided by the Head of the laboratory and the patients Consultant Clinical Geneticist that the presymptomatic test for the familial mutation should be performed and reported • presymptomatic test performed… • NO MUTATION DETECTED, patient at low risk of developing FIF • Report issued 5 weeks after the sample had been received, in time for the clinic date, affected family members not mentioned on the report

9. Now in 2007 • After the report of the Joint Committee on Medical Genetics (April 2006)….. Consent and confidentiality in genetic practice. Guidance on genetic testing and sharing genetic information • The situation is much more clear cut…

10. Guidelines on whole gene screening versus testing for a specific mutationwhen information is available • ‘..best medical practice is to test the consultand for specific mutation or genetic anomaly which has been found in the affected family member(s).’ • ‘..not sensible to undertake a general screen of the consultand’s sample in such circumstances to see if an abnormality can be found.’ • ‘If no anomaly were identified, this could be because the person had not inherited the disorder, or it could be because the techniques employed in the laboratory testing the consultand’s sample was not able to detect the particular type of mutation.’

11. Guidelines for when it is not clear whether there is consent for releasing information • ‘Verifying past consent or newly seeking consent ….may not be possible because contact has been lost or it may not be clinically appropriate….’ • ‘..balance, then must be carefully considered by the health professional and the clinical judgement documented: there may be good reason to believe that more harm may result to a family member by not using the DNA sample or test result, than would result to another member through their use without confirmation that consent had been granted. In these circumstances a sample of extracted DNA and/or the result may be used.’

12. Guidelines when consent is refused • Human Genetic Commission, the Nuffield Council on Bioethics and the GMC have all expressed the view that the rule of confidentiality is NOT absolute’ • ‘In special circumstances it may be justified to break confidence where the aversion of harm by the disclosure substantially outweighs the patients claim to confidentiality’

13. What would we do now? • Perform the presymptomatic test immediately.. • DO NO HARM!!! It would be deleterious to the patient NOT to test for mutation • Final interesting observation…. • Patients father came forward for presymptomatic testing several months after his daughter had her results (unbeknown to him). He was also low risk. If we had had this information the issue with his daughter would not have arisen and the patient and her mother could have been saved unnecessary stress