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3.2. Protocols
Original international and nattonal guidelines (2 7,18) have been revised fol-
lowing the isolation of the HD mutation (19) A number of authors have writ-
ten concernmg their agreed guidelines and clinical programs (24,20-23)
providmg useful mformation for professionals considermg establishing a
presymptomatic testing program. The protocol used m our center is based on
the recommendations of the UK Predictive Testing Consortium for Huntington™s
Disease and is outlined here.
3.2.1. Presymptoma tic Testing Protocol for HD
3 2.1 .l INCLUSION CRITERIA
1 Confirmed family history of HD
2. At risk of HD.
3 Aged 18 yr or over
4. Informed consent freely given
5 Individuals who have previously received counseling
3 2.1.2. POSTPONEMENT CRITERIA
I. Clinically affected with HD
2 Significant risk of suicide
205
Gene& Counseling
3. Recent history of stgmflcant mental illness.
4. Recent htstory of drug mtsuse
5. Recent major hfe events/stressors
3.2.1.3. PRELIMINARY DISCUSSION INTERVIEW
(CLINICAL GENETICIST AND COWORKER)
1 Revrew and update of family and social cncumstances.
2 Informatton booklet explaining the test and research protocol given to apphcant
3 Applicants asked to confirm m writing if they wish to proceed with testmg.
The first interview, conducted by a coworker of the clinical genettctst,
should constst of the followmg elements:
1 Collectton of baste sociodemographtc details Include items on social and medi-
cal history.
2 Confirmatton of family and clinical data (dtscussion of confirmation of mutation
m closest affected relative).
3 Assessment of impact (personal, financial, and social) of HD on the applicant
and, if appropriate, on the partner, and dtscussion of existing coping styles and
resources.
4 Assessment of knowledge (knowledge questionnaire) of HD and presymptomattc
testing. Includes history of learning about HD.
5 Assessment of motivatton (motivation questionnaire) for requesting predtcttve
testing and potenttal impact of results on applicant™s life. To Include dtscusston
of the possibtltty that neurologtcal exammatton may detect early symptoms
6. Detailed explanatton of how the test works, tts posstble outcomes, and tts hmttattons
7 Constderatton of who the applicant will dtsclose the result to
8. Neurological exammatlon and Quantitative Neurological Examination (QNE)
9 First blood sample taken
A second coworker-conducted interview wtll consist of these elements:
1. Further counselmg and dtscusston of prevtously identified problem areas.
2. Explanation of possible results.
3 Review mformal soctal support.
4. Nommation of professtonal supporter who will be wilhng to offer support If and
when necessary
5. Rehearsal of dtsclosure session and travel arrangements.
6. Standardized assessments:
a. Beck Depression Inventory.
b General Health Questtonnatre.
c State Trait Anxiety Inventory
7. Signing of consent form. Copy given to applicant.
8. Blood sample.
9. Specific appointment made for thtrd and fourth interview. Applicant reminded
that he or she can withdraw from testing at any time.
Gray, Soldan, and Harper
206

The thud Interview, at which the coworker will disclose the test results,
should consist of these elements:
1 Applicant to be accompanied by partner / close frrend
2 Disclosure of result by key worker
3 Applicant IS given the opportunny to dtscuss result wtth clinical geneticist
4 Confirm fourth appointment
The mdivtdual should be contacted by telephone 1 wk after dtsclosure, and
clmtcal appomtments should be made 1, 3, and 6 mo and 1 yr after dtsclosure.
There should be a mmtmum of 2 mo between the first and second appointment,
and 2 wk between the second appointment and disclosure.
3.3. Outstanding Problems
As already mentioned, the issues surroundmg testing of those at 25% risk
and the posstble generation of results on intervening parents agamst their
wishes may be difficult to resolve satisfactortly and will mevitably mvolve
careful counselmg and constderatton in mdtvtdual situations. The small chance
of sample mix-up has been addressed m our laboratory by duplicate samples
taken on separate occastons (24). Other problems tdentrfied include presymp-
tomatic testing in patients with various psychiatric disorders, in patients who
are pregnant, and children (2.5,26). It 1salways difficult to define completely
the external pressures on mdivtduals to have presymptomatic testing, although
tdenttticatton of such pressures IS a major aim of the counselmg sessrons.

4. Prenatal Testing
4.1. Issues
The major aim of genetic testing in relation to pregnancy 1sthe clarification
of the genetic options available to the couple, before pregnancy occurs, tf pos-
sible. The avatlabtltty of psychologtcal, medical, and procedural support must
be made clear. Close liaison with the obstetrtc department and the patient™s
general practitioner is vital. When the first contact 1sfor counseling and pos-
sible testing on an already established pregnancy, tt may be extremely dtffcult
to resolve the different issues m terms of testing the pregnancy and the parent
at risk, as indicated below.
In condittons such as HD where mutation testing is now posstble, the poten-
tial use of the less specific exclusion testing still needs consideratron. In our
experience there are sltuattons m pregnancy where exclusron testing 1s prefer-
able to the pregnant couple (27) because tt does not alter the risk of the mter-
vemng parent. The opttons can be difficult to understand and the emottonal
overlay of anxiety about one™s own risk, that of the current pregnancy, and
time pressures only serve to make understanding and constderatton harder.
Gene& Counseling 207

PREGNANCY COUNSELLING PLAN



1
(Time for conslderal/on -AS approprrafe)




$ P
No Test Exclusion
Testing

I
I I
HD No HD In No HD in 50% Risk to Low risk to
HD Pregnancy Pregnancy Pregnancy Pregnancy
A


[ lmplicetion 1 j
;
Termination

Fig 1. Pregnancycounsehngplan

4.2. Protocols
Service protocols are harder to establish in pregnancy because of the limited
time available m prenatal testing and the different problems of individual sttu-
ations. The aim IS to provide counsehng that mforms the mdrvrdual / couple of
the options and enables them to make the best decision for themselves m the
circumstances. The approach 1soutlined m Fig. 1.
4.3. Outstanding Problems
A paper from our center has documented the experiences of, and issues
raised by excluston testing (2 7). Expertence m most centers with prenatal diag-
nosis remains limited and at times traumatic (28). The clmician™s view regard-
ing the desnabihty of termination after a confirmatory diagnosis m the fetus
may be at odds with the patient™s decision. In such situattons, the issues sur-
rounding the clmician™s and the patient™s views regarding termination of an
affected fetus have to be explored fully, and as yet this can still be an area of
controversy. Obviously the major ethical implications of testing a fetus for
such a late-onset conditton remain extremely controverstal for many people.
5. Family Management
By definition, services for genetic disorders need to acknowledge the famtl-
ial context, This 1simportant m relation to clinical management (29) and provt-
ston of genetic counsehng. We have found it important to identify who 1s the
patient when providing services and ensuring contidentiahty. Our resolution
has been to identify the referred patient and ensure that counseling and support
systemsare provided for that mdrvtdual nntially. It has not been our practtce to
208 Gray, Soldan, and Harper

actively contact other family members directly but to allow the mdlvldual to
disseminate mformatlon among relatives. This practice extends to donation
and use of blood samples m testing procedures for family members We feel
that it 1s tmportant to obtain specific signed consent for research use and for
use of blood samples for testing of family members
It IS, however, chmcally invaluable, when providing a genetic service, to
have access to clmlcal family mformatlon. Further to an ascertainment study
(30,31), a confidential register of affected and at-risk family members m Wales
has been established. This is regularly updated and has an important role in the
long-term management of HD m Wales
lmphclt in ldentlfymg and coordinating a support network for affected mdl-
viduals and family members are close liaisons with other professtonal groups,
for example, those referring patients, and those who may be the patlent™s local
and first lme of support and advice Such mdlvlduals obviously include the
primary care health team, psychiatrists, and neurologists.

6. Conclusions
It will be apparent that even wlthm the “archetypal” disorder of HD and m
an established service many questions remam unresolved. We hope that we
have illustrated that despite this a framework can be created for approaching
many of the difficult issues. There are many different views and attitudes
toward the management and testing m late onset neurological disorders but we
have attempted to convey some possible approaches to the clmlcal issues that
we have experienced Collective thought and dlscusslon with colleagues and
patient groups (such as the Huntmgton™s Disease Assoclatlon) about the areas
that we recognize to be contentious 1s very valuable. As previously discussed,
a consortium has been established m the United Kingdom (I 7) m order to effect
such discussion concerning presymptomatlc testing, and proves a very valu-
able resource for those providing a service. Not all the varied situations fit with
the tentative framework we have suggested; mdlvldual situations can be dls-
cussed with such a group and broad consensus often reached regarding the
optimum course of action.

References
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2 Martmdale, B (1987) Huntington™s chorea some psychodynamics seen m
those at risk and m the responses of the helping professlon. Br J Psychzat
150,3 19-332
3 Bloch, M , Adam, S , Fuller, A , Kremer, B., Welch, J P , Wlggms, S , Whyte, P ,
Huggms, M , Thellmann, J , and Hayden, M R (1993) Diagnosis of Huntington
disease a model for the stages of psychological response based on experience of
a predictive testing program Am J Med Genet 47,368-374
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4 Nance, M. A and Ludowese, C J (1994) Diagnosis of Huntmgton™s dtsease
Model for a predictive testing programme based on an understanding of the stages
of psychological response Am. J Med Genet 52, 118-l 19
5 Bekker, H., Modell, M , Denmss, G , Silver, A., Mathew, C., Bobrow, M , and
Marteau, T (1993) Uptake of CF testing m primary care* supply push or demand
pull? Br Med J 306, 1584-1586.
6 Lamport A (1987) Presymptomatic testing for Huntington™s chorea ethical and
legal issues Am J. Med Genet 26,307-314
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disorders: lessons from Huntmgton™s disease FASEB J 6, 28 18-28 19
8 Brandt, J. (1994) Ethical considerations m genetic testing an empirical study of
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Cambridge, pp. 41-59
9 Huggms, M , Bloch, M., Kanam, S., Quarrel, 0 W J , Theilman, J., Hedrtck, A ,
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dtsease Am J Hum Genet 47,412
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commumcation. Am J Med Genet 50,239-246
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genetic counselling, m Genetzc CounselEzng(Lubs, H. A and De la Cruz, F., eds ),
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ing for Huntington™s disease. Am J Med. Genet 54, 167-173
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a retrospective study on psychosocial effects. Am J Med Genet. 44, 94-99.
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Verhage, F. (1993) Presymptomatic DNA testing for Huntmgton™s disease. tden-
I
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dictive testing for Huntington™s disease in Canada: the experience of those receiv-
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tocol of the U. K. Huntmgton™s Prediction Consortium. J Med Genet 29,9 15-9 18
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disease J Mea™ Genet. 31,555-559
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20 Bennett, R L , Bud, T D , and Ten, L (1993) Offering predtcttve testing for
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Counsel 2, 123-137
21 Quatd, K. A (1992) Presymptomatic testing for Huntington™s disease Recom-
mendations for counsellmg. J Genet Counsel 1, 227-301,
22 BenJamln, C M , Adam, S , Wiggins, S , Thetlmann, J L , Copley, T T , Bloch,
M , Squtttert, F , McKellm, W , Cox, S , Brown, S A , Kremer, H P H , et al
(1994) Proceed with care direct presymptomattc testing for Huntington disease
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23 Demyttertaene, K , Evers-Ktebooms, G , and Decryenaene, M. (1992) Pitfalls m
counselling for presymptomattc testing m Huntmgton™s disease Bmh Deficts
Orgtnal Article Series 28, 105-l 11
24 Lazarou, L P , Meredith, A L , Myrmg, J M , Tyler, A , Moms, M , Ball, D. M ,
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