A Mark on the Arm: Myths of Carrier Status in Sibs ofIndividuals With Ataxia–Telangiectasia

Joanna H. Fanos1,2* and Richard A. Gatti3

1Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health,Bethesda, Maryland

2Departments of Pediatrics, Medicine, and Psychiatry, California Pacific Medical Center, San Francisco, California3Department of Pathology, University of California, Los Angeles, California

The ATM gene, mutated in ataxia–telangiec-tasia (A–T), was identified by positionalcloning. The discovery of the ATM gene nowallows the identification of A–T heterozy-gotes [Telatar et al., 1998], who may be atincreased risk of cancer. The purpose of thisstudy was to (a) identify sib’s interest in car-rier testing, (b) explore perception of car-rier status, and (c) assess levels of under-standing of genetics of A–T. This is the sibcomponent of a study of 103 parents and sibs(68 parents and 35 sibs) of individuals withA–T. Thirty-five sibs from 24 families, in-cluding 26 adults and 9 adolescents, drawnfrom the University of California, Los Ange-les, the A–T Clinical Center at the JohnsHopkins University School of Medicine, andthe A–T Children’s Project, were inter-viewed. Eighty-five percent of adult sibsstated correctly that if a child has A–T, bothparents are heterozygotes; 76% knew theA–T gene had been identified. Ninety-twopercent would request carrier testing forthemselves if available. Seventy-nine per-cent would want their child tested for car-rier status prior to the age of 18. Seventy-three percent believed that being a carrieris associated with increased health risks.Sibs have numerous misconceptions sur-rounding carrier status and genetics of A–T.Provision of factual information about ge-netic transmission is necessary, but unfor-tunately insufficient, to counter deeply heldviews of self and others. Genetic counseling,which explores the way in which this infor-mation is filtered and interpreted, could bean effective tool in dispelling family myths.We conclude that A–T sibs need comprehen-

sive support in relation to carrier testing.Am. J. Med. Genet. 86:338–346, 1999.© 1999 Wiley-Liss, Inc.

KEY WORDS: ataxia–telangiectasia; sibs;carrier status; family dynam-ics; genetic counseling; ge-netic testing

INTRODUCTION

Ataxia–telangiectasia (A–T) is an autosomal reces-sive disorder characterized by progressive cerebellarataxia and oculocutaneous telangiectases, as well ascellular and humoral immune deficiencies and an in-creased predisposition to lymphoreticular malignan-cies [Brown et al., 1997]. A–T is diagnosed in 1/40,000to 1/100,000 live births, with a carrier frequency of ∼1%[FitzGerald et al., 1997]. The ATM gene, mutated inataxia telangiectasia (A–T), was identified by posi-tional cloning [Gatti et al., 1988; Lange et al., 1995;Savitsky et al., 1995]. The discovery of the ATM genemakes possible the identification of A–T heterozygotes[Telatar et al., 1998], who may be at increased risk ofcancer [Brown et al., 1997; Gatti et al., 1991; Morrell etal., 1990; Pippard et al., 1988; Savitsky et al., 1995;Swift et al., 1987, 1991]. Screening for A–T carriersmay become controversial, but most likely there will beagreement that those who have a family history of A–Tshould be offered this test. Following the recent modelprovided by cystic fibrosis (CF), pilot studies of A–T-affected families may be most informative before adop-tion of population screening [NIH Consensus Develop-ment Conference, 1997]. Such studies are invaluable inthe development of a successful screening program[Modell, 1990; NIH Workshop on Population Screeningfor the CF Gene, 1990].

Studies have demonstrated a low level of knowledgeof genetics both among individuals undergoing genetictesting [Jung et al., 1994; Nance et al., 1994; Watson etal., 1991], as well as the general population [Decruy-enaere et al., 1992; Denayer et al., 1992]. The public’sdifficulty with understanding probability has been re-

*Correspondence to: Joanna H. Fanos, Ph.D., California PacificMedical Center Research Institute, 2340 Clay Street, San Fran-cisco, CA 94115.

Received 22 March 1999; Accepted 3 June 1999

American Journal of Medical Genetics 86:338–346 (1999)

© 1999 Wiley-Liss, Inc.

ported [Chase et al., 1986; Valverde et al., 1990], andinterpretation of risk is quite variable [Reid et al.,1976]. Research in other genetic disorders such asHuntington disease and cystic fibrosis has demon-strated long-lasting misunderstandings regarding car-rier risks [Fanos, 1996; Fanos and Johnson, 1995a,1995b; Fox et al., 1989; Kessler, 1988]. In A–T, familymyths and private fantasies concerning carrier statuscould have serious consequences by reducing appropri-ate surveillance practices for identified heterozygotes,should they become recommended. Clinical trials of CFpopulation carrier screening have reported wide varia-tions in interest [see Rowley et al., 1997, for an exten-sive review]. In family-based studies of CF, similarvariations were noted [Sorensen et al., 1994; Surh etal., 1994]. Testing of minors in affected families forcarrier status in general is a controversial issue[American Society of Human Genetics and AmericanCollege of Medical Genetics, 1995; Andrews et al.,1994; Clinical Genetics Society (UK), 1994; Fanos1997; Hoffmann and Wulfsberg, 1995; Wertz et al.,1994]. Savitsky et al. [1995] noted that major ethicaland psychological implications of carrier tests for het-erozygosity should be considered. Because of these con-cerns, our study was designed to (a) identify interest incarrier testing in sibs for themselves and their chil-dren, (b) explore perception of carrier status of sibs,and (c) assess levels of understanding of genetics ofA–T in sibs.

METHODSSample

Thirty-five sibs of individuals with A–T were inter-viewed from 24 families, including 26 adults and 9 ado-lescents. This sample was the sib component of a studyof 103 parents and sibs (68 parents and 35 sibs) ofindividuals with A–T. Participants were contacted byRichard Gatti, M.D. (University of California, Los An-geles), Howard Lederman, M.D., Ph.D., and JerryWinkelstein, M.D. (A–T Clinical Center, The JohnsHopkins University School of Medicine, Baltimore,MD). Additional participants were recruited by BradMargus (A–T Children’s Project, Boca Raton, FL). Thestudy protocol was approved by the institutional re-view boards of the participating institutions, and in-formed consent was obtained from all interviewees.

Participants ranged in age from 13 to 71 years (M 425.9, SD 4 12.7). There were 23 females and 12 males.Fourteen of the adult sibs were single; 11 were marriedand 1 was engaged. Only 7 of the adult sibs had chil-dren, with a median of 3. The median education foradult sibs was some college courses. The median house-hold income was $30,000. The sample was 86% Cauca-sian, 9% Hispanic (3 individuals), and 1 respondentwas of Philippine descent. Twenty-seven individualsreported that they had given blood as a part of linkagestudies for identification of the A–T gene; 13 recalledbeing given carrier results sometime during the ensu-ing years. Of those who reported having received re-sults, 7 (27%) understood they were carriers, and 6(23%) understood they were not carriers. The impact ofthis genetic sampling on sibs is explored elsewhere [Fa-nos, 1999].

Standard Psychological Questionnaires

The anxiety and depression scales derived from theHopkins checklist [Derogatis et al., 1971] were used.These measures were developed for use in normal com-munity settings. A large body of literature has demon-strated the stability of the anxiety and depressionscales for various populations. In a random communitysample [Pearlin et al., 1981], exploratory and confirma-tory factor analyses confirmed the distinctiveness ofthe anxiety and depression components.

Questionnaire

Questions were read to sibs concerning their under-standing of the genetic transmission of A–T genetics.Possible responses were yes, no, don’t know (Table I).Respondents were then asked the frequency of A–Tcarrier status in the general population, the incidenceof A–T in affected families, and the frequency of carrierstatus for sibs in affected families (Table II). Sibs werealso questioned as to their beliefs about testing chil-dren for carrier status (Table III), and their beliefs re-garding carrier status for A–T being associated withhealth risks (Table IV).

Qualitative Analysis

All individuals who were willing to participate wereinterviewed separately for approximately 1 hr each. Allinterviews were conducted by J. H. F., taperecordedand transcribed verbatim. The interviews were semi-structured, beginning with very open-ended questionsand moving to more specific probes if material was notforthcoming. For example, all respondents were asked“When you were growing up, did you have any feelingabout whether or not you were a carrier? What wereyour feelings when you received results that you were/were not a carrier?” Based on the interview material,rating scales were developed by J. H. F. on various cat-egories, capturing important aspects of family func-tioning and psychosocial adaptation. These includedcategories of assumptions of carrier status before test-ing and anxiety over potential health problems associ-ated with carrier status, among others. The followingcategories were rated as two possible responses (low/high): anxiety over having A–T, and anxiety over hav-ing children. Two scales were constructed as none/moderate/high: anxiety over their children’s health,and anxiety over heterozygosity linked to health prob-lems. Participants were also rated for their assump-tions of their carrier status prior to being given results(no myths, not a carrier, carrier). Several interviews

TABLE I. Understanding of Genetic Transmission ofAtaxia–Telangiectasia (A–T)

Adult sibs

Yes No Don’t know

If there is a child with A–T,do you believe that bothparents have to be carriers?

22 (85%) 1 (4%) 3 (11%)

If neither parent carries thegene for A–T, can theyhave a child with A–T?

0 (0%) 24 (92%) 2 (8%)

Sibs of Individuals With A–T 339

were selected at random from the sample and given toan outside rater. When a suitable level of reliabilityhad been attained (Kappa above .90), 20 transcribedinterviews were rated by the outside rater. Interraterreliability was obtained on all coded scales and Kappacoefficients ranged from .92 to 1.00 with an overallKappa of .99.

RESULTS

Anxiety and Depression

Anxiety and depression levels in the adults fell sig-nificantly above those of a random normative sample ofcommunity adults [Lieberman and Mullan, 1978]. Thescores on the anxiety and depression scales were posi-tively correlated. There were no significant gender dif-ferences on these scales.

Knowledge (Tables I and II)

Eighty-five percent of adult sibs knew if a child hasA–T, both parents are heterozygotes (Table I). Fifty-four percent stated the frequency of A–T carrier statusin the general population to be higher than it actuallyis, approximately 1% (Table II). Fifty-four percent ac-curately stated that if both parents carry the gene forA–T, the chances are 1:4 for each pregnancy that thechild will be affected. Eighty-four percent underesti-mated carrier risks for sibs in affected families (Table II).

Forty-four percent of adult sibs responded within anacceptable range of prevalence for A–T in the generalpopulation (between 500–1000 diagnosed cases). Forthose whose responses fell outside the acceptablerange, nearly twice as many overestimated the preva-lence. This distortion, perhaps due to lack of “harddata” in the scientific field, or the saliency of their ex-perience, was similar to the responses of sibs with CF

[Fanos and Johnson, 1995a]. Interestingly, teenagersof individuals with A–T were more likely to give re-sponses that were below the acceptable range. As oneteenager pointed out, what had happened to her sisterhad not happened to anyone else she knew.

Knowledge That the Gene for A–T HasBeen Identified

Seventy-six percent of adult sibs knew the A–T genehad been identified. Four individuals (16%) thought ithad not yet been identified, and 2 did not know.

Attitudes Toward Being Tested forCarrier Status

Adult sibs were asked if they would request carriertesting for themselves if testing were to become avail-able commercially. Ninety-two percent of adults saidyes, including the 72% who had already participated inlinkage studies. One respondent said no, and 1 sib wasundecided. The individual who wished not to be testedwas a single male in his mid-20s. His mother died ofbreast cancer when he was a child; his sister died ofA–T several years ago. He thought the frequency ofcarrier status in the population to be one in five. Hedidn’t envision “proliferating” in the near future, andfelt that it would be better to adopt children anyway.Other sibs commented that it would have been helpfulfor them to have that information sooner. As a male,married and without children, explained: “I wish Iknew earlier. ‘Cause you always wonder, am I or am Inot? It would’ve been nice to know, instead of having towonder.” One young woman, in her late 20s and mar-ried, was identified as a carrier several years earlier.The couple wanted to have children, but she was un-

TABLE III. Attitudes Toward Testing Child for Carrier Status

Adult sibs

Childhood(birth–12 years)

Adolescence(13–17 years)

Adulthood(18+ years)

If there were a test to find out whetheryour child is a carrier, when would youwant your child tested?

15 (62%) 4 (17%) 5 (21%)

If you had your child tested, when wouldyou tell him/her the results?

5 (20%) 13 (52%) 7 (28%)

TABLE II. Knowledge of A–T Carrier Status

Adult sibs

Above currentestimate

Currentestimate

Below currentestimate

What is the frequency of A–T carrier status inthe general population?a

14 (54%) 10 (38%) 2 (8%)

If both parents carry the gene for A–T, whatare the chances for each child that he/shewill have A–T?b

6 (23%) 14 (54%) 6 (23%)

Each healthy sib has what percent chance ofbeing a carrier of the A–T gene?c

1 (4%) 3 (12%) 22 (84%)

aCurrent estimate of the frequency of heterozygotes in the general population was ∼1% [FitzGerald et al., 1997].bCorrect answer was 25%.cCorrect answer was 66.7%.

340 Fanos and Gatti

decided about having her spouse tested. She felt that ifshe knew her husband were a carrier, she would not beable to make the choice to “go through that all again,”because she had seen the considerable difficulties in-volved. She felt she would have no choice but to havethe child, because of her feelings for her A–T-affectedsister. “I just couldn’t separate myself from that. If Icould have the test before I had a kid, it’d be like mekilling my sister almost.… It’s almost nice not know-ing, you know?”

Parental Attitudes About Testing Children forCarrier Status for A–T (Table III)

All adult sibs, regardless of whether they had chil-dren, were asked if they would want their child testedif a test were commercially available for identificationof carriers. Seventy-nine percent said they would wishtheir child to be tested prior to the age of 18. More thanhalf preferred testing from birth through age 12, pri-marily so that they might take necessary precautionson behalf of their child, such as avoiding unnecessaryX-rays. Of the 7 adults who had children, 4 would havetheir child tested before 12 years old, 2 during adoles-cence, and 1 after 18.

Sibs were then asked when they would disclose testresults to their child. Only 20% would disclose findingsprior to age 13 regardless of carrier status; 52% wouldtell their child the results sometime during their ado-lescence; 28% would wait either until the child is 18 togive them the results, or they would leave the decisionto be tested to their offspring.

It is important to remember that these are responsesto hypothetical questions concerning attitudes towardtesting; their actual behavior may be quite different.The processes by which they had made their decisionswere complex, at times seemingly based on concerns forhaving affected children at other times out of concernsfor their own potential health risks if identified ascarriers.

Beliefs About Carrier Status and IncreasedHealth Risks (Table IV)

Individuals were asked, “Do you think being a carrierof the A–T gene may be associated with any increasedhealth risks?” In fact, the health risks of A–T carriersare not yet well defined. Although some studies suggesta three- to fourfold increase in breast cancer [Athma et

al., 1996; Swift et al., 1991], and an increased risk ofother cancers, other reports fail to confirm this defini-tively [FitzGerald et al., 1997; Vorechovsky et al.,1996a; Vorechovsky et al., 1996b]. Although the fibro-blasts of A–T carriers show an intermediate range ofradiosensitivity between that of normals and A–T ho-mozygotes [Taylor et al., 1994], there is conflicting evi-dence for clinical radiosensitivity.

Seventy-three percent of adult sibs believed that be-ing a carrier is associated with increased health risks,whereas 27% thought there is no increased risk. If theanswer were positive, respondents were queried as towhich condition(s) might be related to this. Eighty-eight percent stated an association with increased riskof cancer, 19% cited immune disorders, 13% cardiovas-cular problems, and 1 individual mentioned diabetes.Responses concerning cancer risk were most likelybased on past interactions with scientists.

Some sibs, noting tendencies to contract frequentcolds during their childhood, decided that because theyperceived there might be a relationship between im-mune problems and A–T carrier status, they were prob-ably carriers. Two young women, sisters of an indi-vidual with A–T, assumed they were carriers becauseof childhood recurrence of mononucleosis and throatinfections. When the youngest sister learned that shewas not a carrier she was quite surprised, and decidedmaybe she just had a “bad immune system.” One youngman recalled there was a time when he “got a littlecarried away” when he understood that he could be acarrier. He thought that might explain his occasionalunsteadiness of gait, as well as his lack of mental alac-rity:

God, is that why sometimes I don’t always have asgood a balance as.… I mean, is that why I’m justdense about certain things and not as smart as….There were times when I thought, maybe I do havethe gene and maybe there are these as yet uniden-tified, untoward effects on me—there are reasonswhy I am this particular way.

He had recently learned that he is not a carrier.Sixty-five percent of adult sibs of individuals with

A–T believed there was an increased risk of breast can-cer for carriers, whereas 23% thought there was nocorrelation. Not surprisingly, this was a concern articu-lated more by females than males. Although most re-membered either reading or being told of the possiblelink by scientists, some medically sophisticated indi-viduals expressed skepticism until proof could be es-tablished. However, taking note themselves that thereseemed to be a high incidence in their family of rela-tives who had died of cancer, this was an area of someconcern. Interestingly, family history proved to bemore convincing than scientific information, perhapsdue to the greater saliency of personal experience. One21-year-old college student, working in scientific re-search, had learned he was a carrier. He feared hewould die of cancer because both of his grandfathershad already succumbed to this illness: “I always jokearound with my friends, like especially with my girl-friend here, I always joke around about, ‘Well, youknow, I’m going to die when I’m 30.”’ He explained that

TABLE IV. Beliefs Concerning Possible Increased Health Risksfor Heterozygotes

Adult sibs

Yes No Don’t know

Do you think being a carrierof the A–T gene isassociated with healthproblems?

19 (73%) 7 (27%) 0 (0%)

Do you believe that carriersfor the A–T gene are atincreased risk for breastcancer?

17 (65%) 6 (23%) 3 (12%)

Do you believe carriers aremore sensitive to radiationthan other people?

17 (65%) 8 (31%) 1 (4%)

Sibs of Individuals With A–T 341

he was not convinced about the scientific evidence of aconnection of carrier status with increased cancer risk:

All the heterozygote information on A–T couldhave a lot of problems with it. There’s nothing de-finitive about it. And I’m very aware of that. I don’tlose sleep about the fact and really believe that I’mgoing to develop cancer and die at 30. I think morethe reason why I’m going to get cancer is just be-cause my two grandfathers have died of it, otherthan the fact that I’m a carrier for A–T.

When questioned about a possible link between sensi-tivity to certain kinds of radiation and carrier status,65% of adults believed there to be a correlation. How-ever, most reported that this belief had not alteredtheir behaviors to any significant degree, and that at-tention to basic habits of good nutrition and exercise,and avoidance of unnecessary x-rays, were habits theywould have adopted anyway. Some felt that theyshould do more, but in fact did not. As one 33-year-oldman reported, noting that he did not reduce his sunexposure:

I began to understand the heightened risk for cer-tain types of cancers.… Example: Did I stay in thesun less? I like to go to the beach and go swimming,and lay on the beach and read a book. You knowwhat? No, I didn’t. Did I think I should? Yes.

The sample expressed a prevailing belief in a correla-tion between health risks and carrier status. When lev-els of expressed anxiety over health concerns wererated from the qualitative interview material, 65% ofadults had no significant anxiety, while 35% expressedsome. Surprisingly, this was only slightly higher than asample of sibs of individuals with CF, most of whomhad sought carrier testing [Fanos and Johnson, 1995a].When asked about whether the possible link is of con-cern to them, some explained there was too much goingon in their daily lives to worry about it. One woman,when asked if her beliefs caused her much concern,explained that her attention was constantly drawnelsewhere: “Gee, why did they raise the rate here? Whyare we taxed so much? What’s all this mean? We’re toobombarded. Why did the utilities bills go up? It goes onand on. So the answer is no.” For others, an almostfatalistic attitude was expressed. One mother of 3 chil-dren felt there was no point in becoming distressed:

Whatever’s going to happen was formed in my bodyfrom the first time I became an egg, and from thefirst time the egg was planted in my mom’s uterus.It was already designed, what was going to happento me for the rest of my life, and there’s nothing Ican do to change it. Why put any stress on any-body? Why worry?

One man worked with X-rays and was not particularlybothered by this occupational requirement, reportingthat he took no extra precautions. For some individu-als, there seemed to be considerable energy in wardingoff anxiety over this concern. One young man had hisblood drawn when he was about 17, and became heav-ily involved with weight training in college. Whenasked what he appreciated about the sport, he ex-

plained: “The power. The more invincible type feelingagain where you can pick up small cars and stuff likethat. It probably goes back to the whole invincible typething again. Everybody wants to feel invincible.” Hav-ing majored in biology in college, he was studying tobecome a physician’s assistant.

Strikingly, 38% of the adult sample had chosen acareer in one of the medical professions. There was asignificant relationship between choosing a medical ca-reer and anxiety over health problems linked to carrierstatus, x2

df 2 4 9.53, P < .01, with more anxiety amongthose in medicine. It is difficult to know how to inter-pret this finding. It may be that those sibs in the medi-cal profession were more aware of a possible associa-tion, or that early exposure to the medical professionfostered their interest. Alternately, it is intriguing tospeculate that their career in a medical field may havebeen chosen selectively to master the somewhat dis-avowed anxiety over potential health risks of being acarrier.

Perception of Carrier Status

The interview material was rated in terms of wheth-er the sib perceived himself or herself to be a carrierbefore given results. The data sorted into three catego-ries: a belief that he or she was a carrier, a belief thathe or she was not a carrier, or holding no assumptions.Thirty-five percent of adult sibs thought they were car-riers before having given blood, 11% believed they werenot, and 54% held no preexisting beliefs. The relation-ship between perception of carrier status and educa-tion was explored through multiple regression andfound not to be significant, nor was perception of car-rier status and income. These data may be compared toa study of adult sibs of individuals with CF, in which53% of sibs thought they were carriers prior to testing,15% believed they were not carriers, and 32% held nopreexisting beliefs [Fanos and Johnson, 1995a].

Parental Concern for Child’s Health

At the time of the interview, only 7 sibs had children;of those, only 1, a mother of 3 children, reported havingworries that one of her well children might be diag-nosed with A–T. She had no concerns about her littleboy, reasoning that by the time her affected sister washis age, “it was visible in her; you could tell.” However,she did have concerns that one of her daughters hadA–T, because the girl stumbled more than other chil-dren, and shared some physical findings with Tammy,her affected sib. However, for the most part, she wasable to control her fears about her unaffected daughter:

She has these little freckles here, and Tammy hadthose when she was little. And so when I wouldlook at her face real close, I would think of Tammywhen she was little. But, I don’t know, they’re justso different, the kids. I always want to make surethat I don’t group them.

Of interest, none of the 7 adults who had children hadbeen told they were carriers; of the 27% of adults whohad received positive carrier results, none had childrenthus far.

342 Fanos and Gatti

DISCUSSION

The study was designed to (a) identify interest incarrier testing for themselves and their children, (b)explore perception of carrier status of sibs, and (c) as-sess levels of understanding of genetics of A–T in indi-viduals at risk.

Identify Interest in Carrier Testing

The finding that parents would prefer disclosing theresults of carrier testing of their children when theywere teenagers was interesting. Parents reasoned thatthis would allow them adequate time to prepare theirchild for the news if they were carriers, and that itwould allow the child to incorporate results into anemerging self-concept. Drawing upon their personal ex-perience, they recalled it was during adolescence thatthey began thinking about the issue of carrier status,and felt it would be too difficult to understand thisconcept prior to adolescence. Several individualspointed out that until the child was a teenager, a par-ent could ensure that the child take preventive mea-sures related to health risks, but once the child reachesadolescence, he or she would be more responsible formodifying behavior. In addition, knowing that one is acarrier during teenage years would allow time for laterdecisions about having children, or having a futurespouse tested. Many sibs felt that by age 18, they havetheir life “figured out,” and, as one sib suggested, itmight “side rail ’em” and cause depression if they weregiven positive results at that time. One 16-year-old girlexplained that, if parents wait until the child is 18, heor she is likely to be away from home, perhaps at col-lege, and therefore lack family support in processingthe information. Her 19-year-old sister was told duringher freshman year at college that she was a carrier.Reflecting upon her own difficult past experience, shespeculated:

It would affect you more if you’re older and aretold, because you can adjust to it when you’reyounger. You have the time to… you just grow todeal with it, [rather] than all of a sudden, “Bam!You have this much increased risk of cancer, you’llhave kids like this, and everything else.”

She felt that had she been told when she was younger,she would have been accustomed to dealing with thatfact, and “would’ve already thought about it all bynow.”

Explore Perception of Carrier Status

Sibs had grown up with various myths surroundingtheir carrier status. Some individuals assumed thatthey were not carriers, and were shocked to learn theywere. One single man was surprised to receive newsthat he was a carrier because he had always assumedthat he was “the lucky kid.” Having felt indestructible,he did not believe that anything could be amiss for him.One adolescent stated with conviction that he wastested and found not to be a carrier, a view shared byhis father; however, his mother—and the clinician—state that, unfortunately, he is.

Other sibs decided that they were carriers, arriving

at that conclusion through various pathways. Oneteenager was unequivocal in her conviction that shewas a carrier because her mother demonstrated to herthe compelling physical evidence, a small birthmark,similar in appearance to telangiectases:

My mom showed me something on my arm, it’s likea little mark, that shows that I’m an A–T carrier.

One married woman lost her two younger sibs withA–T before she was 15. Identifying with her parents,she always assumed that she must be a carrier, be-cause both of them are obligate heterozygotes. A singlewoman also lost two brothers to A–T. The reason sheassumed she was a carrier was her “sensitivity to any-thing, and how easily, and drastically, I was affected byit.” While growing up, she developed bronchitis or otherrespiratory difficulties every winter. Noting that herA–T-affected brothers dealt primarily with respiratoryproblems, she assumed she must be a carrier. In addi-tion, she realized her mother’s beliefs may have beentransmitted to her: “Maybe I picked up a lot of thatfrom her, and that’s why I think I am. I don’t reallyknow why. I’ve always been so delicate or something, orsensitive. I don’t know.” On the other hand, she sensedthat her unaffected brother was not a carrier becausehe had always been strong, healthy, and vigorous. Inaddition, she has always felt that he is “more our dad’sson, and he’s a lot more like our dad and I’m much morelike our mom.” Interestingly, she was still not married,whereas her brother married and had a child.

Some sibs struggled alone with the meaning of car-rier status as distinct from having the disease, a con-cept difficult for them to grasp. Three of the 9 adoles-cents worried that they might have A–T. One 23-year-old single woman recalled that, prior to her receivingnegative carrier results, she would have “this weirdfeeling what if it [A–T] slowly started to develop … likeif I was walking, like I stumbled or something.” She didnot discuss her worries with her parents, because partof her felt she was being silly. One married woman wasnot surprised to learn she was a carrier. In fact, shealways felt she was because of distressing signs, in-cluding blotches on her arms reminiscent of telangiec-tases, which would appear occasionally, similar tothose of her parents and A–T-affected sister:

I’d try to compare myself against my parents andagainst my sister. I noticed my dad has these littletremors in his hands, and every now and then I’llhave these tremors in my hands. So I alwaysthought, maybe.… Then I’d see little red spots onmy arms, and I’d wonder if that’s because I havethe A–T gene. I bet I do. I’m a klutz too, so maybeI’ve got the A–T gene.

Some individuals reported amnesia of any possible con-versation on A–T within the family. Sibs rememberedthere was an occasion when their parents tried to ex-plain “everything” to them, but they could not recallthe conversation at all. One young woman rememberedthat when she was a teenager, her parents tried todiscuss the illness and genetics with her. She notedwith surprise that, although this occurred only severalyears ago, all she could remember about the conversa-tion was that it had occurred:

Sibs of Individuals With A–T 343

When I was talking to them about this whole thing,I realized I had absolutely no memory of them tell-ing me this information. I knew that they told me,and that’s it. But I … I think that I blocked out theconversation because I don’t remember anythingthey said to me about it.

Wanting to become a psychologist, she had subse-quently learned that she was not a carrier.

Assess Understanding of Genetics of A–T

Misconceptions about the genetic transmission ofA–T were prevalent. This was particularly significantbecause these individuals had been exposed to currenttechnological advances such as recent DNA analysis,and therefore are likely more sophisticated about medi-cal knowledge than the majority of A–T families. Forsome sibs, explanations given in childhood had beendifficult to comprehend. For example, one 22-year-oldwoman attempted with great difficulty to recall the ex-planation she had been offered by her mother about thegenetics of A–T:

You have this certain type of liquid, and you pourmore water into it, and eventually, you know, well,no.… Wait. That was my dad’s version, he didn’tunderstand. I dunno. They were just saying youhave this gene and every once-in-a-while it’ll popback up.

One woman recalled having received a “nice informa-tive booklet” describing the genetic transmission,which she read, but was not sure how much she re-tained. Actually, she reported that females are morelikely to be carriers: “Well, because they are the oneswho carry the baby, and it’s more apt, to my knowledge,to pass on the gene through pregnancy than it would bethrough fertilization. That’s just my theory, I don’tknow.”

For some families, painful genetic realities were in-terpreted by a parent as the other parent’s fault. If thefather had been blamed, A–T was seen as retributionfor past behavioral transgression. For example, onewoman, married and with 1 child, believed that some-how “men’s genes, when they’re born—or when theyare babies—are weaker than women’s,” although shewas unable to remember why this would be so. In herfamily, her father had been blamed for her sib’s illnessbecause he had used various drugs when he wasyounger. Another young woman, married without chil-dren, believed that all the sibs of a child with A–Twould be carriers. Her father also was held accountablefor her sister having A–T because of his prior trans-gressions during the marriage: “When she [her mother]was mad at him, she would say to my dad, or she wouldtell us, ’Your dad committed adultery, that’swhy … that’s what came out … happened to your sis-ter.”’ The blame of the father was linked to actual be-havior, to a perceived breach of ethical conduct. On thecontrary, if the mother bore the brunt of the blame, herculpability was that she had failed at achieving herbiological task, to have a healthy baby. That is to say,

the father had done something, whereas the motherhad not done something. Tragically, assumptions ofcarrier status and of the self, without corrective inter-vention, were passed down from father to child, ormother to child. Although individuals may have re-ceived copious written information on the genetics ofA–T, factual information was viewed through the lensof deeply cherished feelings about self and others. Thisintergenerational transmission of genetic misconcep-tions is poignantly illustrated in the ensuing tale of twogenerations of women in one family. Minor details havebeen altered to protect confidentiality.

Case Example l

Karen was a married woman with two children, oneof whom had A–T. At a young age, Karen began to viewher own mother as a sort of “pathetic, passive person,”easily overwhelmed with problems. She reasoned be-cause she inherited the gene from either her father ormother, and because her mother’s sister had had thedisease, her mother must be the carrier. She felt therewas no question that this complicated her relationshipwith her mother, to whom she did not feel close. In fact,she reported that emotionally she “dismissed” her quiteearly, because she had qualities that she did not ad-mire:

I guess I sort of see her as being … substandard.And then she has this gene. She’s just kind of de-fective. It’s been real hard, it’s been very hard forme to have those feelings and then profess to be aChristian person who wants to love. I want to lovemy mother. I’m just not sure I do.

Karen’s affected daughter was initially diagnosed withmild cerebral palsy; it was not until years later that shereceived the devastating diagnosis that she had A–T.She recalled that as a student, she had had some biol-ogy instruction, when the “little squares, dominant andrecessive” were described: “I could understand intellec-tually what it meant. I think emotionally it’s meantthat somehow I am substandard.” Despite continualreassurances from her husband, she believed thatmaybe her husband should have married someone else:

He’s tall, he’s athletic, he has a wonderful phy-sique, he’s strong. I thought, well, he should havemarried someone who could give him sons, so hecould play catch, teach them how to play tennisand pass on his good genes. I guess I felt that hehad good genes to pass on.

Recently, in a change she attributed to psychotherapy,she has been able to take pleasure in her good quali-ties. For example, she knew she was always bright inschool, and she thought that perhaps intelligence ispassed on from one generation to the next:

A lot of the genes I carry are desirable ones. I’venever had a weight problem. I have good teeth. I’mreally pretty energetic. But, I don’t think I reallywould have seen that if I hadn’t been to a counselorand done things to help me realize that. I felt very,very inferior.

She believed her unaffected daughter, Doris, learned

344 Fanos and Gatti

about genetics when she was in junior high in scienceclasses, where animal breeding was discussed: “Youknow, if you breed this color dog with this color, some ofthe puppies are this color, some are that color, some area mix.” Relying on Doris’ learning about genetics inschool, she did not recall any personal conversation sheever had with her about genetics. “I don’t remembermaking a decision not to tell her. It just never came up.Or maybe I did tell her something. I just don’t remem-ber it. I don’t remember it as being significant.” Karenhopes to make peace with her mother someday.

Her daughter, Doris, described growing up in herfamily as difficult. Realizing her mother had had a dif-ficult childhood, she struggled to understand her moth-er’s difficulties:

I think for her, getting married to my dad was kindof escaping it. I think it really shattered any hopethat she had of having a normal, perfect little fam-ily, and I don’t think my dad came into the mar-riage thinking like that as much as my mom did. Idunno, I feel like it’s broken my mom’s heart more.

Carrier concerns were a major issue for her. She re-membered her mother told her that A–T comes fromher own side of the family, not her father’s; therefore,she always assumed her father was not a carrier.Rather, “the gene passed down from my mom to me.”Doris would become angry at her mother at times andtell her, “I wish you weren’t our mom, because you’rethe one who screwed us all up.” According to her father,she was told she was not a carrier, but she believed shefound out only recently. She made several brief at-tempts at psychotherapy, but became tired of talkingabout the problems in her family.

CONCLUSION

An A–T-affected family presents a challenging envi-ronment in which fears and fantasies about geneticrisk in general and individual carrier status in particu-lar may develop and persevere. Sibs face considerabledifficulties understanding and retaining genetic infor-mation about the disease. Provision of factual informa-tion about genetic transmission is necessary, but un-fortunately, insufficient to counter deeply held views ofthe self and others. Sibs need more direct access tomedical information as well as psychological support inprocessing facts. Genetic counseling, which exploresthe way in which such information is filtered and in-terpreted, could be an effective tool in dispelling familymyths.

ACKNOWLEDGMENTS

We gratefully acknowledge Francis Collins, M.D.,Ph.D., Clair Francomano, M.D., John Johnson, M.D.,and Danilo Tagle, Ph.D. for encouragement and sup-port. We thank Howard Lederman, M.D., Ph.D., JerryWinkelstein, M.D., and Brad Margus for contactingfamilies, Dan Moore, Ph.D. and Maggi Mackintosh forstatistical support, and Laurie Dorsey, Linda Hill, Ju-lie Friedman, Linda Sherwood, and Helen Wills fortechnical support. We thank the families who partici-

pated in this research; their names have been changedto preserve confidentiality. This work was supported inpart by the Visiting Investigator Program, NationalHuman Genome Research Institute, NIH (to J.H.F.),the Division of Intramural Research, NHGRI, NIH,Medical Genetics Branch (to J.H.F.), and funds fromSan Jose State University (to J.H.F.).

REFERENCESAmerican Society of Human Genetics and American College of Medical

Genetics. 1995. Points to consider: ethical, legal, and psychosocial im-plications of genetic testing in children and adolescents. Am J HumGenet 57:1233–1241.

Andrews LB, Fullarton JE, Holtzman NA, Motulksy AG, editors. 1994.Assessing genetic risks: Implications for health and social policy.Washington DC: National Academy Press. p 297.

Athma P, Rappaport R, Swift M. 1996. Molecular genotyping shows thatataxia–telangiectasia heterozygotes are predisposed to breast cancer.Cancer Genet Cytogenet 92:130–134.

Brown KD, Ziv Y, Sadanandan SN, Chessa L, Collins FS, Shiloh Y, TagleDA. 1997. The ataxia–telangiectasia gene product, a constitutively ex-pressed nuclear protein that is not up-regulated following genome dam-age. Cell Biol 94:1840–1845.

Chase GA, Faden RR, Holtzman NA, Chwalow AJ, Leonard CO, Lopes C,Quaid K. 1986. The assessment of risk by pregnant women: Implica-tions for genetic counseling. Soc Biol 33:57–64.

Clinical Genetics Society (UK), Report of a Working Party. 1994. The ge-netic testing of children. J Med Genet 31:785–797.

Decruyenaere M, Evers-Kiebooms G, Denayer L, Van den Berghe H. 1992.Cystic fibrosis: community knowledge and attitudes towards carrierscreening and prenatal diagnosis. Clin Genet 41:189–196.

Denayer L, De Boeck K, Evers-Kiebooms G, Van den Berghe H. 1992.Transfer of information about genetic transmission to brothers andsisters of parents with a CF child. In Birth Defects: Original ArticlesSeries 28:149–158.

Derogatis LR, Lipman RS, Covi L, Rickles K. 1971. Neurotic symptomdimensions. Arch of Gen Psych 24:454–464.

Fanos, JH. 1996. Sibling Loss. Mahwah, NJ: Lawrence Erlbaum Associ-ates.

Fanos JH. 1997. Developmental tasks of childhood and adolescence: impli-cations for genetic testing. Am J Med Genet 71:22–28.

Fanos JH. 1999. The missing link in linkage analysis: the well siblingrevisited. Genet Testing 3:273–278.

Fanos JH, Johnson JP. 1995a. Perception of carrier status by cystic fibrosissiblings. Am J Hum Genet 57:431–438.

Fanos JH, Johnson JP. 1995b. Barriers to carrier testing for adult siblings:the importance of not knowing. Am J Med Genet 59:85–91.

FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, Harkin DP,Finkelstein DM, Isselbacher KJ, Haber DA. 1997. Heterozygous ATMmutations do not contribute to early onset of breast cancer [Letter].Nature Genet 15 (March):307–310.

Fox S, Bloch M, Fahy M, Hayden MR. 1989. Predictive testing for Hun-tington disease: I. Description of a pilot project in British Columbia.Am J Med Genet 32:211–216.

Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F,Foroud T, Jaspers NG, Lange K. 1988. Localization of an ataxia–telangiectasia gene to chromosome 11q22-23. Nature 336:577–580.

Gatti RA, Boder E, Vinters HV, Sparkes RS, Norman A, Lange K. 1991.Ataxia–telangiectasia: an interdisciplinary approach to pathogenesis.Medicine 70(2):99–117.

Hoffmann DE, Wulfsberg E. 1995. Testing children for genetic predisposi-tions: is it in their interest? J Law Med Ethics 23:331–344.

Jung U, Urner U, Grade K, Coutelle C. 1994. Acceptability of carrierscreening for cystic fibrosis during pregnancy in a German population.Hum Genet 94:19–24.

Kessler S. 1988. Invited essay on the psychological aspects of genetic coun-seling. V. Preselection: a family coping strategy in Huntington disease.Am J Med Genet 31:617–621.

Lange E, Borresen A-L, Chen X, Chessa L, Chiplunkar S, Concannon P,Dandekar S, Gerken S, Lange K, Liang T, McConville C, Polakow J,Porras O, Rotman G, Sanal O, Sheikhavandi S, Shiloh Y, Sobel E,Taylor M, Telatar M, Teraoka S, Tolun A, Udar N, Uhrhamer N, Vana-gaite L, Wang Z, Wapelhorst B, Wright J, Yang H-M, Yang L, Ziv Y,

Sibs of Individuals With A–T 345

Gatti RA. 1995. Localization of an ataxia–telangiectasia gene to an∼500-kb interval on chromosome 11q23.1: linkage analysis of 176 fami-lies by an international consortium. Am J Hum Genet 57:112–119.

Lieberman MA, Mullan JT. 1978. Does help help? The adaptive conse-quences of obtaining help from professionals and social networks. AmJ Community Psychol 6:499–517.

Modell B. 1990. Cystic fibrosis screening and community genetics. Am JMed Genet 27:475–479.

Morrell D, Chase CL, Swift M. 1990. Cancers in 44 families with ataxia–telangiectasia. Cancer Genet Cytogenet 50:119–123.

Nance MA, Sevenich EA, Schut LJ. 1994. Knowledge of genetics and atti-tudes toward genetic testing in two hereditary ataxia (SCA 1) kindreds.Am J Med Genet 54:242–248.

NIH Consensus Development Conference, Genetic Testing for Cystic Fi-brosis. April 14–16, 1997.

NIH Workshop on Population Screening for the Cystic Fibrosis Gene. 1990.N Engl J Med 323:70–71.

Pearlin LI, Lieberman MA, Menaghan EG, Mullan JT. 1981. The stressprocess. J Health Soc Behav 22:337–356.

Pippard EC, Hall AJ, Barker DJP, Bridges BA. 1988. Cancer in homozy-gotes and heterozygotes of ataxia–telangiectasia and xeroderma pig-mentosum in Britain. Cancer Res 48:2929–2932.

Reid KJ, Sakati N, Prichard LL, Schneiderman LJ, Jones OW, Dixson BK.1976. Genetic counseling—An evaluation of public health genetic clin-ics. West J Med 124:6–12.

Rowley PT, Loader S, Levenkron JC. 1997. Cystic fibrosis carrier popula-tion screening: a review. Genet Testing 1:53–59.

Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Z, Vanagaite L, Tagle DA,Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, HarnikR, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L,Sanal O, Lavin MF, Jaspers NGJ, Taylor AMR, Arlett CF, Miki T,Weissman SM, Lovett M, Collins FS, Shiloh Y. 1995. A single ataxia–telangiectasia gene with a product similar to PI-3 kinase. Science 268:1749–1753.

Sorenson JR, Devellis BM, Cheuvront JB, Callanan NP, Talton SL. 1994.Carrier testing among CF patients’ first and second degree relatives.Am J Hum Genet 555:A22.

Surh LC, Cappeli M, MacDonald M, Mettler G, Dales RE. 1994. Cysticfibrosis carrier screening in a high-risk population: participation basedon a traditional recruitment process. Arch Pediatr Adol Med 148:632–637.

Swift M, Reitnauer PJ, Morrell D, Chase C. 1987. Breast and other cancersin families with ataxia-telangiectasia. N Engl J Med 316:1289–1294.

Swift M, Morrell D, Massey RB, Chase CL. 1991. Incidence of cancer in 161families affected by ataxia–telangiectasia. N Engl J Med 325:1831–1836.

Taylor AMR, McConville CM, Rotman G, Shiloh Y, Byrd PJ. 1994. A hap-lotype common to intermediate radiosensitivity variants of ataxia–telangiectasia in the UK. Internatl J Radiat Biol 66:S35–S44.

Teletar M, Teraoka S, Wang Z, Chun HH, Liang T, Castellvi-Bel S, Udar N,Borresen-Dale A-L, Chessa L, Bernatowska-Matuszkiewicz E, PorrasO, Watanabe M, Junker A, Concannon P, Gatti RA. 1998. Ataxia–telangiectasia: identification and detection of founder-effect mutationsin the ATM gene in ethnic populations. Am J Hum Genet 62:86–97.

Valverde K, Gilbert F, Denning C. 1990. Cystic fibrosis carrier detection: apilot program testing public attitudes and action toward the diseaseand testing. Am J Hum Genet 47(Suppl):A125.

Vorechovsky I, Luo L, Lindblom A, Negrini M, Webster DB, Croce CM,Hammarstrom L. 1996a. ATM mutations in cancer families. Canc Res56:4130–4133.

Vorechovsky I, Luo L, Prudente S, Chessa L, Russo G, Kanarious M, JamesM, Negrini M, Webster ADB, Hammarstrom. 1996b. Exon-scanningmutation analysis of the ATM gene in patients with ataxia–telangiectasia. Eur J Hum Genet 4:352–355.

Watson EK, Mayall ES, Chapple J, Dalziel M, Harrington K, Williams C,Williamson R. 1991. Screening for carriers of cystic fibrosis throughprimary health care services. Br Med J 303:504–507.

Wertz DC, Fanos JH., Reilly PR. 1994. Genetic testing for children andadolescents: who decides? JAMA 272:875–881.

346 Fanos and Gatti