Genetic Counselling and Predictive testing for Huntington’s Disease

1. Genetic Counselling and Predictive testing for Huntington’s Disease Ruth Glew 18 November 2011 Understanding and managing Huntington’s Disease in a multidisciplinary Environment

2. Overview • The genetics of HD • Role of genetics services • Predictive testing • Prenatal diagnosis • Family implications • Who and how to refer

3. Common myths • HD affects only females/males • HD skips generations • ‘If I am similar to my affected parent I am more likely to be affected’ • ‘If I have no symptoms by age 40yrs I will be OK’

4. Inheritance

5. Autosomal dominant inheritance mother unaffected father affected gene with alteration working copy of gene 50:50chance the child will inherit the disease from the father

6. The Huntington’s Disease Gene 1 ttg ctg tgt gag gca gaa cct gcg ggg gca ggg gcg ggc tgg ttc cct ggc cag cca ttg 61 gca gag tcc gca ggc tag ggc tgt caa tca tgc tgg ccg gcg tgg ccc cgc ctc cgc cgg 121 cgc ggc ccc gcc tcc gcc ggc gca cgt ctg gga cgc aag gcg ccg tgg ggg ctg ccg gga 181 cgg gtc caa gat gga cgg ccg ctc agg ttc tgc ttt tac ctg cgg ccc aga gcc cca ttc 241 att gcc ccg gtg ctg agc ggc gcc gcg agt cgg ccc gag gcc tcc ggg gac tgc cgt gcc 301 ggg cgg gag acc gcc atg gcg acc ctg gaa aag ctg atg aag gcc ttc gag tcc ctc aag 361 tcc ttc cag cag cag cag cag cag cag cag cag cag cag cag cag cag cag cag cag cag 421 cag cag cagcaa cag ccg cca ccg ccg ccg ccg ccg ccg ccg cct cct cag ctt cct cag

8. Age of onset • Variable – average 30-50yrs • Anticipation • Juvenile HD • HD in older age

9. What is genetic counselling Genetic counselling is the process of helping people understand and adapt to the medical, psychological and familial implications of a genetic diagnosis. This process integrates the following: Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence. Education about inheritance, testing, management, prevention, resources and research. Counselling to promote informed choices and adaptation to the risk or condition.

10. Being at risk • period of adjustment to risk • uncertainty • possible altered life plans • burden of care • potential discrimination/stigma ANXIETY

11. Referrals • 31yr man, mother died last year of HD. He is Schizophrenic ? related to substance misuse. He wants genetic counselling for himself and as regards his children. • 17 yr girl wants wheels put in motion for her to have test for HD. Mother has tested positive for the gene and grandmother is affected • 61 yr lady discovered brother diagnosed with HD. She is anxious for her own immediate family and extended members and is requesting screening • 40yr lady known to have HD gene. She feels she has some abnormal movements and is having a difficult time with depression. • 32yr lady had positive predictive test, is now pregnant and wants prenatal diagnosis • 39yr man detained HMP mother died HD. He has past psychiatric history. Has had CT scan and needs to be seen for genetic testing as he is concerned about his future. • 47yr man, mother has HD and he is aware of implications, he is unsure whether or not he should have formal testing. • 14yr boy, father had HD and committed suicide, he would like further information regarding the condition and possible testing. Hew lives with foster parents.

12. REFERRAL GENETIC COUNSELLOR CONTACT: family pedigree family experience of HD prior knowledge families questions GENETICS CLINIC APPOINTMENT: information risks options where to go from here TESTING Predictive/prenatal/diagnostic CONTINUED FOLLOW-UP annual H/V, clinic appt, tel contact

13. Predictive testing for HD

14. What is predictive testing? Common features: • currently healthy • at risk of genetic condition • predicting the future • shortened life expectancy • right not to know/to know • reproductive decision making • experience of previous generations

15. Why is predictive testing taken so seriously? • HD is at present untreatable • Having the altered gene means developing the disorder • Loss of the ‘get out’ clause • Long term effects: emotionally, socially & financially • Risk of adverse reaction WFN/IHA guidelines 1994 – testing only in regional genetics centres Knowledge once given can never be taken away

16. Predictive testing protocol • Minimum of 2 appointments • 2 months between each appointment • DNA sample at 2nd appointment • results available 4 weeks after appointment two • follow-up at 1 week, 1 month, then negotiated with patient Appt 1 Appt + Appt 2 ? Follow-up f/up cont’ + ve Discharge -ve

17. Pre test discussion • Confirm diagnosis • Rationale for testing • Experience of HD and risk • Benefits/disadvantages of testing • Implications – personal, family, social and financial (telling children) • Plans for future/decisions resting on result • Coping skills/support network • Supporters feelings • Coexisting stressors • Explanation of outcomes/ examination/post test

18. Follow-up choices following P/S test • No follow up at present • Within Genetics HD clinic/district clinic/GC • Asymptomatic clinic (Anne Rosser) -assessment and research

19. UK data

20. HD Pre-symptomatic Test Figures (1993 - 2010) Number oftests Year -

21. Pre-symptomatic tests - Age Distribution 1994 and 2010

22. HD Pre-symptomatic testing - Prior Risk (2010) • 50% risk n = 358 • 25% risk n = 23 • Other n = 19

23. HD Pre-symptomatic testing - Sex Distribution (2010) • 2010 male 45% n= 179 female 55% n= 223 • 1993-2010 male 44% female 56%

24. HD Pre-symptomatic Testing - Outcome (2010) 2010 Exp = 223 Normal = 175 RP = 16 Int = 22 Exp/Int = 2

25. Reasons for testing 2010 • A - decrease uncertainty • B - plan future • C - family planning • D - possible therapy • E - inform family • F - other

26. Other more challenging issues • 25% risk • Testing of minors • Mental health problems • Learning difficulties • Difficult family dynamics • Individuals unaware of symptoms or in denial

27. Prenatal testing and Pre-implantation Genetic diagnosis (PGD) • Prenatal testing at 11 or 15 weeks of pregnancy (15-20 tests a year UK) • Only if couple wanting to end pregnancy if foetus affected • PGD - IVF technology to re-implant unaffected embryo’s

28. Clinical Cases

29. Case 1 JAMES 50+yrs Diag’ 20’s P+ SION DAWN TINA FFION NATASHA P+ P+ P+

30. Case 2 HAROLD BEN LIAM P-

31. JILL 65yrs Diag 70yrs

32. HD Clinical Pathway REFERRAL INDIVIDUAL AT RISK ? DIAGNOSIS/ASYMP’ GENE CARRIER RESEARCH AFFECTED GC PRECLINIC CONTACT pedigree, consents and molecular confirmation DISTRICT GENETIC CLINIC HDPREDICTIVE TEST CLINIC ASYMPTOMATIC GENE + CLINIC MANAGEMENT CLINIC withdrawal result DISTRICT F/UP DISCHARGE REGULAR F/UP OPEN ACCESS REGULAR F/UP

33. Who to refer? • Individuals with a new diagnosis • How to tell the family? • How to tell the children? • Individuals at risk • Those who want more information about HD and/or their options • Those who want a test • Those who don’t want to risk passing it on • Those who are symptomatic, but in denial

34. Referrals to: Professor A Clarke. Department of Medical Genetics University Hospital of Wales Heath Park Cardiff CF14 4XW Tel 02920 742577