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Guidelines for the Molecular Genetics Predictive Test in Huntington's Disease

NEUROLOGY 1994;44;1533-1536

Foreword: Recommendations concerning the use of a predictive test for the detection of Huntington's disease (HD) were drawn up by a committee consisting of representatives of the International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington's Chorea.

The establishment of a committee with the specific task of preparing such guidelines was agreed upon at the WFN and IHA conferences in Lille, France, in September 1985. The first recommendations were adopted by each of the organizations at their respective meetings in Vancouver, BC, Canada, June 30 to July 3, 1989, and published in the JOURNAL OF THE NEUROLOGICAL SCIENCES (1989;94;327-332) and the JOURNAL OF MEDICAL GENETICS (1990;27;34-38).

Revision of these guidelines was necessary in view of the report, published in March 1993, of the detection of the gene defect.

Present and original members of the committee are as follows in alphabetical order: Jytte Broholm (Denmark), Jean-Jacques Cassiman (Belgium), David Craufurd (UK), Arthur Falek (USA), Carys Farmer-Little (France/UK), Michael Hayden (Canada), Robyn Kapp (Australia), Kai Krahnen (Germany), Ascuncion Martinez-Descals (Spain), Marion Mol (Belgium), Nitnos Myrianthopoulos (USA), Henry Petit (France), Kimberly Quaid (USA), Chris De Somviele (Belgium), Elaine Taylor (Canada), Audrey Tyler (UK), Ralph Walker (Canada), Loe Went (Holland), and Nancy Wexler (USA)

Introductory Remarks

  1. The present document provides realistic, ethical principles based on current knowledge and techniques in molecular genetics.

  2. We are convinced that the different sections of these recommendations are inextricable parts of a whole. The test should be offered only if all the recommended provisions are available.

  3. These recommendations are set forth by members of the HD family organizations and the biomedical community as guidelines to protect at-risk individuals; therefore, it is of the utmost importance that the guidelines are at all times available to these individuals so that they can freely make informed decisions.

  4. The guidelines are also intended to assist clinicians, geneticists, and ethical committees as well as lay organizations to resolve difficulties arising from the application of the test. The committee is willing to provide advice on problems related to the interpretation of these guidelines.

  5. In these guidelines, use of the DNA test for diagnostic purposes - eg. in the case of a suspicious or uncertain clinical picture - has not been considered. But it may have a profound (predictive) effect on siblings and other relatives.

Recommendations Comments
1. All individuals who may wish to take the test should be given up-to-date, relevant information so that they can make an informed, voluntary decision. 1. Counseling of the highest standards should be available in each country. It is recommended that, as a standard medical practice, informed consent for the test be documented with the signature of the person to be tested and the professional responsible for the counseling.
2. The decision to take the test is solely the choice of the individual concerned. No requests from third parties - family members or otherwise - shall be considered. 2. The individual must choose freely whether to be tested and must not be coerced by family, friends, partners or potential partners, physicians, insurance companies, employers, governments or others.
2.1 The test is available only to individuals who have reached the age of majority (according to the laws of the respective country). 2.1 A prenatal test may constitute an exception to this role. Testing for the purpose of adoption should not be permitted, since the child to be adopted cannot decide for himself or herself whether to be tested. It seems appropriate and even essential, however, that the child be informed of his or her at-risk status upon reaching the age of reason.
2.2 Each participant should be able to take the test regardless of his or her financial situation. 2.2 Each national lay organization should use its influence with government departments, public and private health insurers, and other organizations to reach this goal.
2.3 Individuals should not be discriminated against in any way as a result of genetic testing for HD.
2.4 Extreme care should be exercised when testing would provide information about another person who has not requested the test. 2.4 This issue will arise when a child at 25% risk requests testing with full knowledge that his or her parent does not want to know his or her own status. Every effort should be made by the counselors and the individuals concerned to arrive at a satisfactory resolution of this conflict. A considerable majority of representatives from the lay organizations feel that if no consensus can be reached, the right of the adult child to know should have priority over the right of the parent not to know.
2.5 For applicants with evidence of a serious psychiatric condition, it may be advisable that testing be delayed and support services put into place.
2.6 Testing for HD should not be part of a routine blood investigation without the specific permission of the subject. 2.6 Such specific permission should in principle also be required for symptomatic individuals.
2.7 Ownership of the test results remains with the individual who requested the test. Legal ownership of the stored DNA remains with the person from whom the blood was taken. 2.7 The consent form should address this issue. Local legal opinions may be helpful.
2.8 All laboratories are expected to meet rigorous standards of accuracy. They must work with genetic counselors and other professionals providing the testing service. 2.8 The lay organizations can provide an inestimable service in inquiring about the standards of the laboratory and can assist individuals who want to be or have been tested with their inquiries and concerns.
2.9 The counselors should be specifically trained in counseling methods and form part of a multi-disciplinary team. 2.9 Such multi-disciplinary team should consist of, eg, a geneticist, a neurologist, a social worker, a psychiatrist, and someone trained in medical ethical questions.
3. The participant should be encouraged to select a companion to accompany him or her throughout all stages of the testing process: the pretest stage, the taking of the test, the delivery of results, and the post-test stage. 3. This companion may be the spouse/partner, a friend, a social worker, or any individual who has the confidence of the participant. It may not be appropriate for the companion to be another at-risk individual.
3.1 The counseling unit should plan with the participant a follow-up protocol that provides for support during the pre- and post-test stages regardless of whether the participant chooses a companion. 3.1 Support should be available close to the individualıs community.
4. Testing and counseling should be provided within specialized genetic counseling units knowledgeable about molecular genetic issues in HD, preferably within a university department. These centers should work in close collaboration with the lay organizations of the country. 4. Often the test will be conducted at a site other than the counseling center. If no lay organization exists in the country, the center should contact the IHA.
4.1 The laboratory performing the test should not communicate the final results to the counseling team until very close to the time such results are to be revealed to the participant. 4.1 The aim is to protect the participant from the possibility of counseling bias at any time (see also comment 5.2.5).
4.2 Under no circumstances shall any member of the counseling team or the technical staff communicate information concerning the test or its results to third parties without the written permission of the applicant. 4.2 Only in the most exceptional circumstances (ie, prolonged coma, death, and the like) may information about the test results, if so requested, be provided to family members.
4.3 Neither the counseling center nor the test laboratory should establish direct contact with a relative whose DNA may be needed for the purpose of the test without permission of the applicant. All precautions should be taken when approaching such a relative.
5. Essential information 5. Essential information is information that is absolutely vital to the whole test procedure.
5.1 General information 5.1 This information should be presented both orally and in written form and be provided by the team responsible for the testing service.
5.1.1 On HD, including the wide range of its clinical manifestations, its social and psychological implications, its genetic aspects, options for procreation, availability of treatment, and so forth. 5.1.1 It must be pointed out that at this time neither prevention nor cure is possible.
5.1.2 On the implications of nonpaternity (and nonmaternity). 5.1.2 Genetic testing may show that the putative parent is not the biologic parent; this should be brought to the attention of the applicant and discussed. With the availability of techniques such as in vitro fertilization, even cases of nonmaternity may occasionally be discovered.
5.1.3 On support and information available from lay organizations, including their documentation on HD, addresses for help and social contacts, and so forth. 5.1.3 If no lay organization exists in the country, contacts can be made with the IHA or a lay organization in a neighboring country.
5.1.4 Psychosocial support and counseling must be available before the test procedure commences. 5.1.4 Lay organizations should be mentioned as an additional source of support and information.
5.2 Information pertaining to the test.
5.2.1 How the test is done.
5.2.2 Possible need for DNA from one other affected family member and the possible problems arising from this. 5.2.2 Asking an affected individual, who may be unaware of or unwilling to acknowledge his or her symptoms, to contribute a blood sample may be an invasion of privacy.
5.2.3 The limitations of the test (error rate, the possibility of an uninformative test, and so forth).
5.2.4 The counselor must explain that, although the gene defect has been found, at the present time no useful information can be given about age at onset or about the kind of symptoms, their severity, or their rate of progression. 5.2.4 Much more information will be needed about the implications of the number of repeats.
5.2.5 The predictive test indicates whether someone has or has not inherited the gene defect, but it does not make a current clinical diagnosis of HD if the gene is present. 5.2.5 Particular care should be taken with participants who are believed to be showing early symptoms of HD; however, individuals with established, unacknowledged symptoms should not automatically be excluded from the test and should receive additional counseling.
5.3 Information on consequences. 5.3 All consequences have to be discussed - those related to the presence or the absence of the gene defect as well as those related to not taking the test.
5.3.1 For the participant himself or herself.
5.3.2 For the spouse/partner and children. 5.3.2 If the companion of the participant is not his or her spouse/partner, special consideration should be given to such spouse/partner.
5.3.3 For the affected parent and his or her spouse. 5.3.3 The feelings of this affected parent, who may well become aware of the results, must be taken into account.
5.3.4 For the other members of the participantıs family. 5.3.4 Whatever information is obtained, it will influence the feelings of other relatives and the participantıs relationship with them.
5.3.5 Socioeconomic consequences of the test results, including potential employment, insurance, social security, data security, and other problems.

5.4 Information on alternatives the applicant can consider.

5.4.1 Not to take the test for the time being.

5.4.2 To deposit DNA for research.

5.4.3 To deposit DNA for possible future use by family and self.

5.4.4 DNA deposited under 5.4.2 above would be made available to the donorıs family members at their request after the death of the donor if it is essential to obtain an informative result.

5.4.5 In the case of DNA deposited under 5.4.2 or 5.4.3 above, the unit collecting the DNA must provide a written declaration that samples will not be used for purposes other than those specified in the said declaration with the exception of the provisions of 5.4.4.

6. Important preliminary investigations.

6.1 It is important to verify that the diagnosis of HD in the family of the individual is correct.

6.2 Neurologic examinations and psychological appraisal are considered important to establish a baseline evaluation of each individual. Any other specialized tests are always noncompulsory; refusal may not affect participation in the test.

7. Antenatal diagnosis

6.2 Refusal to undergo these and other additional examinations will not justify the withholding of the test from applicants.
7.1 It is essential that antenatal testing for the HD mutation be performed only if the parent has already been tested. For a possible exception, see recommendation 7.3 7.1 It is highly desirable that both parents agree to an antenatal test. If there is a conflict, every effort should be made by the counselors and the couple to reach an agreement. Exceptional circumstances (eg. rape or incest) may justify deviating from this recommendation.
7.2 The couple requesting antenatal testing must be clearly informed that if they intend to complete the pregnancy if the fetus is a carrier of the gene defect, there is no valid reason for performing the test. Furthermore, this situation is contrary to recommendation 2.1, since a child thus born with the gene defect cannot elect not to take the test upon reaching majority. 7.2 Testing a fetus carries with it a small additional risk of miscarriage and, possibly, of congenital abnormality.
7.3 Test centers may still perform an exclusion test for a future pregnancy if a 50% at-risk person specifically requests it. For this test, the at-risk individual and the partner, parents, and fetus are tested only with adjoining DNA probes.

8. The test and delivery of results.

7.3 The purpose of the exclusion test, which was frequently performed before the gene defect itself had been found, is to permit a 50% at-risk person to exclude the possibility of having affected children without changing his or her 50% at-risk status. This includes the termination of pregnancies where the fetus is 50% at-risk and continuation of pregnancies where the fetus is only at low risk.
8.1 Excluding exceptional circumstances, there should be a minimum interval of 1 month between presentation of the pretest information and the decision whether or not to take the test. The counselor should ascertain whether the pretest information has been properly understood and should take the initiative to be assured of this. However, contact will be maintained only at the applicantıs request.

8.2 The result of the predictive test should be delivered as soon as is reasonably possible after completion of the test, on a date agreed upon in advance by the center, the counselor, and the participant.

8.3 The manner in which results will be delivered should be discussed by the counseling team and the individual.

8.4 The participant has the right to decide, prior to the date fixed for the delivery of the results, that these results shall not be revealed to him or her.

8.5 The results of the test should be revealed in person by the counselor to the individual and his or her companion. No result should ever be revealed by telephone or by mail. The counselor must have sufficient time to discuss any questions with the individual.

8.6 All post-test provisions (see section 9) must be available from the moment the test results are revealed.

9. Post-test counseling.

9.1 The frequency and the form of post-test counseling should be discussed by the team and the participant prior to performance of the test, but the participant has the right to modify the planned program. Although the intensity and frequency will vary from person to person, post-test counseling must be available at all times.

9.2 The counselor should have contact with the individual within the first week after delivery of the results, regardless of the nature of the results.

9.3 If there is no further contact within 1 month of the delivery of the test results, the counselor should initiate the follow-up.

9.4 It is essential that post-test counseling be made available regardless of the participantıs financial situation.

9.5 The lay organization has an important role to play in the post-test period. The information and support that it can provide should always be offered to the participant regardless of whether he or she belongs to that organization.

8.1 Antenatal testing may be one such exceptional circumstance. Such an interval is necessary to give the individual sufficient time to assimilate the pretest information in order to make an informed decision. During this interval, specialists from the test center must be available for further consultation.


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