Genetic Counselling and Predictive testing for Huntington’s Disease

Ruth Glew18 November 2011

Understanding and managing Huntington’s Disease in a

multidisciplinary Environment

Overview

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

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’

Inheritance

Autosomal dominant inheritancemother

unaffectedfather

affected

50:50 chance the child will inherit the disease from the father

gene with alteration

working copy of 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 cag caa cag ccg cca ccg ccg ccg ccg ccg ccg ccg cct cct cag ctt cct cag

The Huntington’s Disease Gene

Age of onset

• Variable – average 30-50yrs• Anticipation• Juvenile HD• HD in older age

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.

Being at risk

• period of adjustment to risk • uncertainty• possible altered life plans• burden of care• potential discrimination/stigma

ANXIETY

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.

REFERRAL

GENETIC COUNSELLOR CONTACT:family pedigree family experience of HDprior knowledge families questions

GENETICS CLINIC APPOINTMENT:information risksoptions where to go from here

TESTINGPredictive/prenatal/diagnostic

CONTINUED FOLLOW-UPannual H/V, clinic appt, tel contact

Predictive testing for HD

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

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 reactionWFN/IHA guidelines 1994 – testing only in

regional genetics centres

Knowledge once given can never be taken away

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 2

?Follow-up

Discharge-ve

f/up cont’+ ve

Appt +

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

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

UK data

HD Pre-symptomatic Test Figures (1993 - 2010)

195

615

537570

498

372 386 365

454

376404 392 381 371 387

342

431

615

0

100

200

300

400

500

600

700

199319941995199619971998199920002001200220032004200520062007200820092010

Year -

Num

ber

of te

sts

Pre-symptomatic tests - Age Distribution 1994 and 2010

0

5

10

15

20

25

30

35

>20 21-30 31-40 41-50 51-60 61-70 <70

age

perc

ent

of w

hole

1994

2010

HD Pre-symptomatic testing - Prior Risk (2010)

• 50% risk n = 358

• 25% risk n = 23• Other n =

19

89%

5%

6%

HD Pre-symptomatic testing - Sex Distribution (2010)

• 2010male 45% n= 179female 55% n= 223

• 1993-2010male 44%female 56%

55%

45%

HD Pre-symptomatic Testing - Outcome (2010)

2010Exp = 223Normal = 175RP = 16Int = 22Exp/Int = 2

Normal51%

Expanded40%

RP4% INT

5%

Reasons for testing 2010

207

171

70

16

104

15

0

50

100

150

200

250

A B C D E F

• A - decrease uncertainty

• B - plan future• C - family planning• D - possible therapy• E - inform family• F - other

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

in denial

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

Clinical Cases

Diag’ 20’s

P+ P+

P+

P+

Case 1

DAWN TINA FFION NATASHA SION

JAMES 50+yrs

Case 2

BEN

HAROLD

LIAM

P-

Diag 70yrsJILL65yrs

REFERRAL

INDIVIDUAL AT RISK ? DIAGNOSIS/ASYMP’ GENE CARRIER

RESEARCH AFFECTED

GC PRECLINIC CONTACTpedigree, consents and molecular confirmation

DISTRICT GENETIC CLINIC

MANAGEMENT CLINIC

HD PREDICTIVE TEST CLINIC

ASYMPTOMATICGENE + CLINIC

withdrawal result

REGULAR F/UP

DISCHARGE REGULAR F/UP

DISTRICT F/UP

OPEN ACCESS

HD Clinical Pathway

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

Referrals to:

Professor A Clarke.Department of Medical GeneticsUniversity Hospital of WalesHeath ParkCardiffCF14 4XWTel 02920 742577