J Med Genet 1999;36:615–620 615

Carrier testing of children for two X linked J Med Genet: first published as 10.1136/jmg.36.8.615 on 1 August 1999. Downloaded from diseases in a family based setting: a retrospective long term psychosocial evaluation

Outi Järvinen, Anna-Mari Aalto, Anna-Elina Lehesjoki, Mikael Lindlöf, Ismo Söderling, Antti Uutela, Helena Kääriäinen

Abstract ing children. Advantages include creating The question of whether genetic carrier opportunities for children to adjust to their testing should be performed on children situations, fostering of openness within fami- has been the subject of much debate. lies, relief of parental uncertainty, and compre- However, one important element has been hensiveness of family testing. Disadvantages lacking from this debate. There has been include possible harm to a child’s self-esteem, practically no knowledge of how those distortion of family perception of a child, and tested in childhood have experienced car- deprivation of choice in adulthood of deciding rier testing. Twenty three subjects in whether to be tested.2 No data have been avail- families aVected by Duchenne muscular able about how those tested in childhood have dystrophy and 23 in families aVected by reacted to the experience. A, all of whom had been There have been several studies of the tested during childhood for carriership in psychosocial consequences of carrier testing of the Department of Medical Genetics, Uni- adult family members, and of population versity of Helsinki, from 1984 to 1988, par- screening for carriers of recessive diseases, such The Family Federation ticipated in our study. We investigated as cystic fibrosis,3–7 Tay-Sachs disease,89 â of Finland, long term psychosocial consequences of thalassaemia,10 and sickle cell trait.11 No serious Department of carrier testing in childhood. A question- adverse eVects have been found in the studies Medical Genetics, PO naire relating to sociodemographic back- Box 849, FIN-00101 cited, but various degrees of anxiety have been Helsinki, Finland ground and life situation was used, found to be associated initially with detection O Järvinen together with assessment of health related of carriership. Anxiety mostly seems to decline H Kääriäinen quality of life (HRQOL) using the RAND with time.347Some carriers have been found to 36 item Health Survey 1.0 (RAND). RAND have less positive feelings about themselves,5 or STAKES, Health results showed that the emotional, social, their current health,6 and less optimistic views Services Research 9 Unit, Helsinki, Finland and physical well being of the young about future health than non-carriers. In a http://jmg.bmj.com/ A-M Aalto female subjects was not statistically diVer- study of experience of carrier testing for X ent from those of control female subjects linked disorders in adulthood, non-carriers Department of at a similar age. We also found no statisti- were found to feel emotional relief, but carriers Medical Genetics, cally significant diVerences in means in felt sadness and loss of reproductive University of Helsinki, any RAND dimension (p<0.146) between 12 Helsinki, Finland expectations. A-E Lehesjoki carriers, non-carriers, and a group in There have been very few studies of the psy- which carrier status was uncertain. How- chosocial consequences of carrier testing or Folkhälsan Institute of ever, two out of seven carriers reported screening during adolescence.13 16 In two, carri- on September 23, 2021 by guest. Protected copyright. Genetics, Helsinki, that they were worried and three that they ers were initially found to experience anxiety, Finland were slightly worried about the test result. 13 16 A-E Lehesjoki which declined with time. However, pro- Four out of 22 young female subjects in the longed worry about carrier status and regret at Helsinki University uncertain group reported being worried having been tested have also been reported.14 Central Hospital, and 11 reported being slightly worried. Only one report of the psychosocial conse- HD-Laboratories, (J Med Genet 1999;36:615–620) quences of genetic carrier testing in childhood Division of Medical has been published. It concerns retrospective Genetics, Helsinki, Keywords: carrier testing in childhood; health related Finland quality of life; psychosocial consequences; RAND evaluation of testing of carriers of balanced M Lindlöf chromosomal rearrangements through inter- view of members of 10 nuclear families. Learn- The Population When a child is diagnosed as suVering from a ing about carrier status had caused transient Research Institute, hereditary disease, its parents usually want to psychological disruption, accompanied by feel- Helsinki, Finland 1 17 I Söderling know about the carrier status of healthy sibs. It ings of unjustified stigmatisation. The results has been, and probably still is, common of this study and of studies in which carrier National Public Health practice to test sibs for possible carriership.2 testing was evaluated during adolescence Institute Finland, The British Working Party of the Clinical suggest that testing causes no serious distress Helsinki, Finland Genetics Society has suggested that the carrier or clinically important levels of anxiety. A Uutela status of children should not be determined More information about the consequences Correspondence to: solely in relation to possible future of genetic testing in childhood is obviously Dr Järvinen. reproduction.2 This suggestion has been fol- needed. The aim of our study was to determine lowed in Finland and, presumably, adopted in whether there had been any long term psycho- Received 27 August 1998 Revised version accepted for most western countries. However, justifications social consequences of carrier testing per- publication 22 March 1999 can be advanced for both testing and not test- formed eight to 12 years previously in female 616 Järvinen, Aalto, Lehesjoki, et al

Table 1 Numbers and age at testing of children in families the case of HB. The young female subjects aVected by Duchenne muscular dystrophy and haemophilia tested were sisters or cousins of aVected males. J Med Genet: first published as 10.1136/jmg.36.8.615 on 1 August 1999. Downloaded from A who responded Age at the time of testing ranged from 1 to 17 Age at testing (y) DMD Haemophilia Total years. Of the 66 young females who were over 15 years old at the time of our study, 46 5–6 3 2 5 7–8 5 2 7 participated in the questionnaire study. Ages of 9–10 3 2 5 respondents to our questionnaire at the time of 11–12 3 4 7 carrier testing are shown in table 1. 13–14 1 6 7 15–16 4 3 7 17 4 4 8 CONTROLS Total 23 23 46 The Finnish female population of the same age was used for control purposes since infor- children and teenagers in families with X mation concerning sociodemographic charac- linked recessive diseases (Duchenne muscular teristics and health related quality of life as dystrophy (DMD) or Becker muscular dystro- measured by RAND (see Methods) from 1996 phy (BMD) and (HA) or B was available.24 Carriers, non-carriers, and (HB)). The main variables studied were those in whom test results had been uncertain emotional well being, social and physical func- were also compared. tioning, general health, marital status, and reproductive behaviour. METHODS Contacting families Subjects and methods The parents of families were approached by DISEASES mail by the doctor who had counselled them at DMD and BMD are X linked recessive the time of testing. They were asked to inform muscular dystrophies. DMD occurs in boys their daughters about the study and ask under 5 years of age and causes progressive whether they would be willing to participate. muscle weakness, usually leading to the death The subjects tested (mostly adult at the time of of subjects in their 20s from respiratory our study) were therefore contacted only via complications. Age of onset of BMD is later their parents. A questionnaire with a reply paid and life spans are longer. Both progressive dis- return envelope was sent to daughters who eases are usually considered diYcult and consented, provided that they were at least 15 depressive for families.19 years old. If no reply had been received within HA and HB are X linked recessive six weeks, a reminder was sent. Letters and disorders. AVected subjects easily and questionnaires were mailed and received back suVer joint and muscle haemorrhages, pro- between October 1996 and February 1997. longed bleeding from wounds, and excessive, Families who did not reply were subsequently sometimes fatal, haemorrhages after trauma. contacted by telephone. Improvements in the treatment of haemophilia over the past 20 years have considerably http://jmg.bmj.com/ changed the prognosis. Nevertheless, haemo- The questionnaire philia remains a chronic, often serious, The questionnaire contained some 100 ques- disease,18 and life long replacement therapy for tions, mostly multiple choice, the rest open the deficient factor is needed. ended. The first part of the questionnaire con- With X linked recessive inheritance, only sisted of items relating to sociodemographic males are aVected but female relatives can be background, life situation, and testing of health related quality of life (HRQOL) by means of carriers. Any sons of symptom-free female car- on September 23, 2021 by guest. Protected copyright. riers have a 50% chance of being aVected. It is the RAND 36 item Health Survey 1.0 25 often possible to perform genetic tests on (RAND). The multi-item RAND scale relates healthy female family members, even in child- to eight aspects of quality of life: (1) physical hood, to determinate carrier status. There are functioning, (2) role limitations related to two basic methods of studying carriership, physical health, (3) role limitations related to direct testing and linkage studies. emotional problems, (4) energy/fatigue, (5) The former confirms or excludes carriership emotional well being, (6) social functioning, with certainty. The latter is associated with (7) pain, and (8) general health. The scale has varying degrees of uncertainty. been translated into Finnish and adapted to the Finnish culture.24 Possible concern about the PARTICIPANTS result of testing was evaluated by the question: Our study involved two groups of young “If you were a carrier or your test result was women who had undergone genetic carrier uncertain, are you worried about it?” The testing during childhood in the 1980s in question had five possible answers (yes, Finland. Thirty nine children in 30 families slightly, cannot say, indiVerent, no). The with DMD or BMD were tested for carriership remainder of the questionnaire was intended to in the Department of Medical Genetics, evaluate experiences relating to testing, and University of Helsinki, from 1984 to 1988,22 23 how test results were comprehended by the by means of direct mutation analysis or linkage children tested. Results in this connection will studies. During the same period, 46 children in be reported later. 38 families with HA or HB were tested for carriership,20 21 also by means of direct muta- Statistical methods tion analysis or linkage studies in the case of All RAND scores were transformed linearly HA, but solely by means of linkage studies in into values ranging from 0 to 100, as suggested Carrier testing in children 617

FAMILIES WITH HAEMOPHILIA J Med Genet: first published as 10.1136/jmg.36.8.615 on 1 August 1999. Downloaded from

GENETIC CARRIER TESTING HAD 46 CHILDREN HAD BEEN TESTED (34 BEEN PERFORMED IN 38 FAMILIES were over 15 years old at the time of our study)

IN THESE FAMILIES 40 CHILDREN HAD 33 FAMILIES WERE REACHED BEEN TESTED (28 were over 15 years old at the time of our study)

25 YOUNG FEMALE SUBJECTS WHO 27 FAMILIES REPLIED HAD BEEN TESTED RECEIVED THE QUESTIONNAIRE

23 COMPLETED THE QUESTIONNAIRE

FAMILIES WITH DUCHENNE MUSCULAR DYSTROPHY

GENETIC CARRIER TESTING HAD 39 CHILDREN HAD BEEN TESTED (32 BEEN PERFORMED IN 30 FAMILIES were over 15 years old at the time of our study)

IN THESE FAMILIES 36 CHILDREN HAD 27 FAMILIES WERE REACHED BEEN TESTED (29 were over 15 years old at the time of our study)

24 YOUNG FEMALE SUBJECTS WHO 22 FAMILIES REPLIED HAD BEEN TESTED RECEIVED THE QUESTIONNAIRE http://jmg.bmj.com/

23 COMPLETED THE QUESTIONNAIRE

Figure 1 Participation in study. by Hays et al.25 Higher values represented bet- ception of carriership by the respondents was ter physical, mental, or social functioning and assessed by a question: “What was the result of

well being. genetic carrier testing?” There were eight pos- on September 23, 2021 by guest. Protected copyright. Respondents were divided into six groups sible answers: (1) I am a carrier (risk over based on disease and carrier status: haemo- 95%), (2) I am at very high risk of being a car- philia carriers/non-carriers/those in whom test rier (risk 90 to 94%), (3) I am at high risk of results had been uncertain, and muscular dys- being a carrier (risk 60 to 89%), (4) I am at trophy carriers/non-carriers/those in whom test moderate risk of being a carrier (risk 20 to results had been uncertain. The subjective per- 59%), (5) I am at low risk of being a carrier (risk 5 to 19%), I am not a carrier (risk under Table 2 Results of telephone interview with seven mothers who did not respond to letter or questionnaire 5%), (7) the test result remained uncertain, (8) cannot say. The carrier group consisted of Why did the mothers not reply? those who considered themselves to be carriers One mother said that she did not receive the questionnaire or at over 90% risk of being carriers. Non- Two mothers did not like the questionnaire One mother was angry about the questionnaire, because it brought back bad memories (her carriers were those who, after having been aVected son had died) tested, understood the risk of their being carri- One mother forgot to post the questionnaire ers to have been excluded or to be very low Two mothers said that there were many very personal questions, which made them reluctant to reply (under 5%). The uncertain group consisted of What did the mothers think about carrier testing? those who had understood that the risk of their Two mothers said that it might not be a good idea to test children being carriers could be neither excluded nor Four mothers thought carrier testing was a good idea confirmed (risk 5 to 89%). For analysis, One mother was disappointed because carrier status remained unresolved respondents were divided on the basis of their What was the test result? 6/11 non-carrier subjective perceptions of carrier status, rather 4/11 carrier than an objective test result, because the 1/11 uncertain former reflects more closely what they believe. How many young female subjects tested in this group had not been told about their test result All analyses were conducted using SPSS for Of 11 young female subjects tested, 6 had not been told the results of their test Windows, version 7.0. Analysis of variance was 618 Järvinen, Aalto, Lehesjoki, et al

Table 3 Sociodemographic descriptions of 37 respondents 18 to 29 years of age and of serious psychosocial problems aVecting the Finnish women of similar ages lives of the young women. J Med Genet: first published as 10.1136/jmg.36.8.615 on 1 August 1999. Downloaded from

Duchenne muscular Haemophilia A Controls dystrophy (n=18) (n=19) (%) SOCIODEMOGRAPHIC CHARACTERISTICS OF Level of education RESPONDENTS Primary education 7 (39%) 13 (68%) 38 The mean age of young female respondents in Upper secondary education 11 (61%) 6 (32%) 61 the families with DMD was 21.7 years (SD 4.2 Marital status Single 8 (44%) 7 (37%) 54 years) and in the families with HA it was also Married/cohabiting 10 (56%) 12 (63%) 45 21.7 years (SD 3.5 years). Sociodemographic Employment status characteristics are shown in table 3. The young Employed 3 (17%) 9 (47%) 35 female subjects in the families with HA had Unemployed 3 (17%) 1 (5%) 13 Student/at school 8 (44%) 6 (32%) 43 more often had only primary education and Other (housewife) 4 (22%) 3 (16%) 5 were more often cohabiting or married than the Children young female subjects in the families with No children 13 15 DMD or the controls. Four out of seven carri- Pregnant 1 1 One or more children 5 4 ers, 10/17 non-carriers, and 7/22 subjects in Children/woman (mean) 0.50 0.50 0.39* the uncertain group were married or cohabit- Maternal level of education† ing. Primary school 4 (22%) 6 (32%) 48* The nearest relative reported to be aVected Vocational education 13 (72%) 9 (47%) 43* Academic education 1 (6%) 1 (5%) 6* was a brother in the case of 30 respondents Unknown 3 (16) (65%). In the families aVected by DMD, the *Data from Statistics Finland (from 1996). nearest relative reported to be aVected was a †Maternal level of education was used to describe the social backgrounds of subjects. brother in the case of 18 respondents (78%) and in the families aVected by HA 12 of the used to compare means of RAND scores respondents (52%). There were usually also between carriers, non-carriers, and the uncer- other aVected subjects in the families. Four tain group. DiVerences in HRQOL were brothers with DMD had died. analysed using the non-parametric Mann- Of the 46 young women tested, 11 had had Whitney test, in relation to testing age and age at least one child or were pregnant. This was at which test results were communicated (age the case in 2/7 carriers, 6/17 non-carriers, and groups 5 to 12 years and 13 to 29 years), mari- 3/22 of the uncertain group. tal status, level of education, and whether a brother was aVected. In comparing the HRQOL of the young HEALTH RELATED QUALITY OF LIFE women tested to that of controls, the 95% con- Initially, all RAND scores for the young female fidence intervals for means of scores for each subjects tested, who were 18 to 29 years old at HRQOL dimension for those who had been the time of our study, in the case of both diseases were compared separately with scores

tested were compared with the 95% confidence http://jmg.bmj.com/ intervals for means for controls. for controls. There were no controls for RAND in the age group 15 to 17 years. When 95% confidence intervals for the means of all RAND Results scores were compared, the psychosocial well PARTICIPATION being of the subjects in our study was not sta- Fig 1 illustrates participation in the study. All tistically diVerent from that of the controls respondents were from families with DMD or (table 4). Similarly, when the means of all

HA, as there were few families aVected by RAND scores were correlated with level of on September 23, 2021 by guest. Protected copyright. BMD or HB. We telephoned mothers of the education, marital status, and occupation, families who did not reply, to determine none of the diVerences between the groups was whether our study population was biased. We statistically significant. The age groups 17 to 23 were able to reach seven out of nine mothers by and 24 to 29 did not diVer significantly from telephone. These seven mothers had 11 each other. daughters tested. Table 2 summarises the Secondly, means were compared for all responses of the mothers. The mothers re- RAND scores for all of the young female sub- ported that 4/11 of the young women tested jects tested, divided into carriers, non-carriers, had got married, one carrier (of HA) had had and uncertain group members, in families with three children, and one carrier (of HA) had had DMD and HA separately (table 5). None of the an aVected child. The mothers mentioned no diVerences between the groups was statistically

Table 4 Health related quality of life: the study group (haemophilia A (HA) and Duchenne muscular dystrophy (DMD) separately) versus control group

Study group 95% CL* Study group 95% CL* RAND dimension DMD (n=18) HA (n=19) Controls 95% CL* Role functioning (emotional) 72.9–101.1 75.0–102.8 73.4–82.2 Emotional well being 72.1–84.3 73.6–87.2 70.2–74.5 Social functioning 86.3–98.4 85.7–97.1 83.0–87.9 Energy/fatigue 63.7–76.9 65.2–80.6 60.7–65.4 General health 72.8–87.2 72.6–88.5 73.8–78.1 Physical functioning 92.6–101.5 96.4–100.4 93.6–96.9 Role functioning (physical) 81.2–102.1 71.6–102.1 84.3–91.3 Bodily pain 82.1–94.5 80.2–96.7 80.0–85.5

*95% confidence interval for mean; no significant diVerence was found. Carrier testing in children 619

Table 5 Health related quality of life (carriers v non-carriers v uncertain) J Med Genet: first published as 10.1136/jmg.36.8.615 on 1 August 1999. Downloaded from

Mean scores (SD)

RAND dimension Carrier (n=5) Non-carrier (n=7) Uncertain (n=11) p value

Duchenne muscular dystrophy Physical functioning 98.0 (4.5) 95.0 (13.2) 99.5 (1.6) 0.513 Physical role functioning 100 89.3 (28.3) 93.2 (16.2) 0.642 Energy/fatigue 77.0 (14.0) 72.9 (9.9) 62.7 (18.4) 0.190 Emotional role functioning 100 90.5 (25.2) 81.8 (31.1) 0.433 Emotional well being 83.2 (13.1) 79.4 (10.7) 74.5 (13.3) 0.425 Social functioning 93.8 (12.5) 92.9 (12.2) 92.0 (12.8) 0.972 Bodily pain 86.0 (15.2) 94.3 (7.9) 88.1 (12.5) 0.445 General health 82.0 (22.8) 79.3 (10.6) 80.0 (13.7) 0.953

Carrier (n=2) Non-carrier (n=10) Uncertain (n=11) p value

Haemophilia A Physical functioning 100 97.5 (5.4) 98.2 (3.4) 0.753 Physical role functioning 87.5 (17.7) 87.5 (31.7) 86.4 (32.3) 0.996 Emotional role functioning 100 86.7 (32.2) 93.3 (21.1) 0.753 Energy/fatigue 75.0 (7.0) 78.5 (12.3) 68.2 (17.8) 0.312 Emotional well being 80.0 (5.7) 86.4 (5.1) 74.5 (17.9) 0.146 Social functioning 81.3 (8.8) 91.3 (10.3) 90.9 (13.8) 0.557 Bodily pain 80.0 (14.1) 95.0 (10.8) 80.0 (22,8) 0.165 General health 82.5 (3.5) 77.5 (14.0) 77.7 (21.0) 0.932

Analysis of variance, p<0.01.

significant (p value greater than 0.146 for all Mendelian disorder does not result in hesita- groups using analysis of variance). tion as regards marriage. Thirdly, all RAND scores for the study The RAND scores show that the young population were calculated by marital status, female subjects tested had at least as good by level of education, by testing age and age at emotional, social, and physical well being as the which the test results were communicated, and controls. Our study therefore shows that carrier by whether a brother was aVected, for the two testing resulted in no measurable distress to the diseases separately. Results were analysed using subjects tested. However, it has been argued the non-parametric Mann-Whitney test. No that such a finding can mean two things: either statistically significant diVerences between that the psychosocial well being of the partici- groups were found. pants was in fact very good, or that the result Finally, two out of seven carriers (29%) reflected defensive denial of the participants.26 reported that they were worried and three Many subjects apparently live and cope well (43%) that they were slightly worried about the through such defensiveness, which becomes

test result. Four out of 22 young female part of their normal lives. http://jmg.bmj.com/ subjects (18%) in the uncertain group reported No statistically significant diVerences in being worried and 11 (50%) reported being means between carriers, non-carriers, and slightly worried. members of the uncertain group existed in relation to any RAND score (p>0.146), but the Discussion groups may have been too small for signifi- This is the first study of late psychosocial con- cance to be demonstrable. The RAND test has been widely used in

sequences of genetic carrier testing for an X on September 23, 2021 by guest. Protected copyright. linked disorder in childhood. various studies, for instance in evaluating 27 28 The young female subjects tested appeared HRQOL in a random population sample 29–33 to diVer in respect to some sociodemographic and in patients with diVerent diseases. The characteristics from the controls. The controls advantage of such a generic battery of tests is were more often single and less often house- the possibility it allows of comparing popula- wives than the young women tested. They had tions of interest with normal populations of had more education than the young women in similar ages.34 35 RAND is considered to be the families with HA. These diVerences could comprehensive, with sensitivities and validities have aVected RAND scores. better than those of many other generic test The young women who had been tested in batteries (for example, the Quality Well-being the families with HA were more often married Scale, the Rosser Index, or the Sickness Impact or cohabiting (63%) than those in the families Profile) because it explores several dimensions with DMD (56%) or controls of the same age in relation to quality of life, and there are more (45%). Being married or cohabiting was than two response options for each question.34 equally common in the group of carriers (4/7) Although the RAND test is regarded as reliable and in the group of non-carriers (10/17), but for evaluating HRQOL,34 comprehensive inter- less common in those in whom test results had viewing of a group of the young female subjects been uncertain (7/22). In a previous study on tested would extend our study results. the eVect of Tay-Sachs heterozygosity on mari- There are three limitations to our study tal status in young adults 21 to 26 years of age, population. Firstly, the small number of young it was found that 32% of carriers were engaged women studied limited the possibility of or married, as opposed to 16% of detecting diVerences between subgroups. Since non-carriers.14 These results would seem to the diseases concerned are rare, the study indicate that identification as a carrier of a material could not be extended. Secondly, 620 Järvinen, Aalto, Lehesjoki, et al

telephone interviews with mothers who did not 7 Denayer L, Welkenhuysen M, Evers-Kiebooms G, Cassi- man JJ, van den Berghe H. The CF carrier status is not J Med Genet: first published as 10.1136/jmg.36.8.615 on 1 August 1999. Downloaded from complete a questionnaire or pass one to their associated with a diminished self-concept or increased daughters showed that the families were anxiety: results of psychometric testing after at least 1 year. Clin Genet 1996;49:232-6. selected, in that 6/11 daughters had not been 8 Childs B, Gordis L, Kaback MM, Kazazian HH Jr. told about the test result. Thirdly, a better con- Tay-Sachs screening: social and psychological impact. Am J trol group would have been untested sisters or Hum Genet 1976;28:550-8. 9 Marteau TM, Van Duyn M, Ellis I. EVects of genetic cousins of aVected male subjects. Such a group screening on perceptions of health: a pilot study. JMed could not be formed, because practically all Genet 1992;29:24-6. 10 Rowley PT, Lipkin M Jr, Fisher L. Screening and genetic such subjects in the entire country had been counseling for beta-thalassaemia trait in a population unse- tested at the time. lected for interest: comparison of three counseling methods. Am J Hum Genet 1984;36:677-89. The results of the study reported here show 11 Wooldrige EQ, Murray RF. The health orientation scale: a that the young female subjects tested had measure of feeling about sickle cell trait. Soc Biol 1989;35: 123-36. experienced good emotional, social, and physi- 12 Williams JK, Schutte DL. Benefits and burdens of genetic cal well being in their lives. However, most of carrier identification. Western J Nursing Res 1997;19:71-81. 13 Clow CL, Scriver CR. Knowledge about and attitudes those who were carriers or members of the toward genetic screening among high-school students: the uncertain group reported being concerned Tay-Sachs experience. Pediatrics 1977;59:86-91. about the results of testing. In our study popu- 14 Zeesman S, Clow CL, Cartier L, Scriver CR. A private view of heterozygosity: eight-year follow-up study on carriers of lation, no respondent reported severe symp- the Tay-Sachs detected by high-school screening in toms, such as psychiatric illness, severe anxiety, Montreal. Am J Med Genet 1984;18:769-88. 15 Cobb E, Holloway S, Elton R, Raeburn JA. What do young or attempted suicide. In an evaluation of the people think about screening for cystic fibrosis? JMed consequences of identifying children as carriers Genet 1991;28:322-4. 16 Mitchell J, Sevier RC, Clow CL, Kaplan F. What young of balanced chromosomal rearrangements con- people think and do when the option for cystic fibrosis car- ducted by interviewing the subjects tested at rier testing is available. J Med Genet 1993;30:538-42. 17 Jolly A, Parsons EP, Clarke A. Testing children to identify least 10 years afterwards, it was found that carriers of balanced chromosomal translocations. JMed learning about carrier status had caused Genet 1996;33:suppl 1. 18 Ginsburg D. Haemophilias and other disorders of homeo- transient psychological disruption, but that stasis. In: Ramona LD, Condor JM, Pyeritz RC, eds. Emery after 10 years some subjects were indiVerent to and Rimoin’s principles and practice of medical genetics. New York: Churchill Livingstone, 1997. their carrier status, while others reported 19 Dubowitz V. The muscular dystrophies. In: 17 Muscle disorders feelings and experiences of stigmatisation. in childhood. London: Saunders, 1995. 20 Lehesjoki AE, Rasi V, de la Chapelle A. Haemophilia B; There have been some studies relating to diagnostic value of RFLP analysis in 19 of the 20 known screening or carrier testing of recessive diseases Finnish families. Clin Genet 1990;38:187-97. during adolescence.13–16 It is diYcult, and may 21 Lehesjoki AE, Sistonen V, Rasi V, de la Chapelle A. Hemo- philia A: genetic prediction and linkage studies in all avail- even be impossible, to compare the results of able families in Finland. Clin Genet 1991;39:199-209. our study with the results of the studies cited 22 Lindlöf M, Kääriäinen H, Davies KE, de la Chapelle A. Carrier detection and prenatal diagnosis in X linked mus- because screening or carrier testing was carried cular dystrophy using restriction fragment length polymor- out in a completely diVerent context. phisms. J Med Genet 1986;23:560-72. 23 Kääriäinen H, Lindlöf M, Somer H, de la Chapelle A. Our retrospective investigation showed that Genetic counselling in Duchenne and Becker muscular genetic carrier testing during childhood re- dystrophy is problematic when carrier studies give contro- versial results. Clin Genet 1990;37:179-87. http://jmg.bmj.com/ sulted in no measurable disturbance of quality 24 Aalto AM, Aro AR, Teperi J. RAND-36 Terveyteen liittyvän of life in adulthood. The study population was, elämänlaadun mittarina; luotettavuus ja suomalaiset väestöar- vot. STAKES (in press). however, fairly small. Evaluation of a larger 25 Hays RD, Sherbourne CD, Mazel RM. The RAND 36-Item group through international collaboration Health Survey 1.0. Health Econ 1993;2:217-27. 26 DudokdeWit AC, Tibben A, Duivenvoorden HJ, Niermeijer might yield more meaningful results. Absence MF, Passchier J,Trijsburg RW and the Rotterdam/Leiden of evidence of adverse eVects cannot be Genetics Workgroup. Distress in individuals facing predic- tive DNA testing for autosomal dominant late-onset considered as a reason for proceeding with disorders: comparing questionnaire results with in-depth

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