genetic counselling and predictive testing for huntington’s disease
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Genetic Counselling and Predictive testing for Huntington’s Disease. Ruth Glew 18 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 - PowerPoint PPT PresentationTRANSCRIPT
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