issues surrounding prenatal genetic testing for achondroplasia

PRENATAL DIAGNOSISPrenat Diagn 2002; 22: 933–940.Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/pd.437

Issues surrounding prenatal genetic testing forachondroplasia

Holly C. Gooding1, Karina Boehm2, Richard E. Thompson3, Don Hadley1, Clair A. Francomano4 andBarbara Bowles Biesecker1*1Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA2Office of Communication and Health Education, National Institute for Dental and Craniofacial Research, National Institutes ofHealth, Bethesda, MD, USA3Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA4Human Genetics and Integrative Medicine Section, National Institute of Aging, National Institutes of Health, Baltimore,MD, USA

Objectives Mutations in the gene encoding fibroblast growth factor receptor 3 cause achondroplasia, themost prevalent form of dwarfism. Since the discovery of the mutations and gene in 1994, commercial testinghas been available for use in prenatal diagnosis. This study sought to determine the awareness of, interest inand use of prenatal genetic testing for achondroplasia.

Methods Surveys were collected from both individuals affected with achondroplasia (n = 189) and theiraverage statured relatives (n = 136).

Results The majority of participants were aware of the prenatal genetic testing at the time they were surveyed,but less than 10% had actually used the testing. Affected individuals were much more interested in using thetesting if they became pregnant (62%) than were their relatives (28%). The groups were remarkably similarin their interest in using the testing to identify the lethal, homozygous form of achondroplasia and in theirunwillingness to consider termination of pregnancies based on a diagnosis of either achondroplasia or averagestature. Affected status and perception of the condition were correlated with the importance placed on knowingthe prenatal diagnoses of achondroplasia and average stature. Views on abortion were highly correlated withall aspects of interest in prenatal diagnosis for achondroplasia.

Conclusion These results elucidate the role of selected attitudes and beliefs that contribute to reproductivedecision making about achondroplasia. Furthermore, the findings provide insights into education and counselingissues for families and health care practitioners. Copyright 2002 John Wiley & Sons, Ltd.

KEY WORDS: achondroplasia; prenatal genetic testing; reproductive decisions; illness perception

INTRODUCTION

Achondroplasia is a skeletal dysplasia affectingapproximately one in every 25 000 births and is themost common dwarfing syndrome (Gorlin et al., 1990).An individual with achondroplasia is disproportionatelyshort, with a proportionately large head and long trunkin contrast to shortened limbs. Final adult height forthose affected with achondroplasia averages four feet forboth men and women. Other noteable physical featuresinclude frontal bossing, lumbar lordosis, genu varusand shortened hands and feet. While related physicalconditions include delayed motor milestones, middleear infections, respiratory difficulty, spinal stenosisand fatigue, people with achondroplasia exhibit normalcognition and overall physical development (Gorlinet al., 1990; Committee on Genetics, 1995; Castiglia,1996).

Achondroplasia is inherited in an autosomal dominantmanner, with 75–90% of cases due to sporadic

*Correspondence to: Barbara Bowles Biesecker, NHGRI/NIH,10 Center Drive, Building 10, Room 3C710, Bethesda, MD20824, USA. E-mail: [email protected]

mutations (Murdock, 1970). Couples of average heightwho give birth to a child with achondroplasia havea low risk for recurrence resulting from gonadalmosaicism (Mettler and Fraser, 2000), while individualswith achondroplasia have a 50% chance of passingthe altered gene on to each child. When bothparents have achondroplasia, there is a 25% risk ofhomozygous achondroplasia, a condition with severeskeletal abnormalities that is fatal within the first monthsof life (Castiglia, 1996). Because marriage betweenaffected individuals is common (Ablon, 1984), manypeople with achondroplasia are at risk for conceiving achild with the homozygous form. Until recently, affectedcouples could choose not to know the status of thefetus before birth, to rely on prenatal diagnosis ofachondroplasia through ultrasound, to use reproductivetechnologies such as artificial insemination or spermor egg donation, or to choose not to have biologicalchildren and adopt children (Committee on Genetics,1995).

In 1994 it was discovered that achondroplasia iscaused primarily by one mutation in the fibroblastgrowth factor receptor 3 (FGFR3 ) gene on humanchromosome 4 (Rousseau et al., 1994; Shiang et al.,

Copyright 2002 John Wiley & Sons, Ltd. Received: 5 July 2001Revised: 6 April 2002

Accepted: 6 May 2002

934 H. C. GOODING ET AL.

1994). Further work by Webster and Donoghue (1996)developed the theory that the resulting glycine to argi-nine substitution in the transmembrane domain of theFGFR3 protein results in constitutive activation of thereceptor. This unregulated activation of an important sig-nal transduction pathway is hypothesized to lead to theabnormal cartilage growth plate differentiation seen inthe long bones of people with achondroplasia (Web-ster and Donoghue, 1996). Bellus et al. (1995) foundthat, of 154 unrelated individuals with achondroplasiastudied, 97% had a G to A transition at nucleotide1138 in the FGFR3 gene. Two subjects had a G to Ctransversion at the same nucleotide location and one hadno detectable mutation at all (Bellus et al., 1995). Thenearly single mutation nature of this condition allowedfor rapid development of clinical diagnostic testing forachondroplasia.

No systematic collection of data has been undertakenon the actual uptake of this testing, and there has beenno formal research to date on issues surrounding theinterest in this testing by individuals with and withoutachondroplasia. Factors influencing interest in prena-tal diagnosis for achondroplasia and the reproductivepreferences of those who might use this testing needto be assessed in order to better understand the edu-cation and counseling needs of potential testing users.Therefore, we sought to characterize issues surroundingprenatal genetic testing for achondroplasia by survey-ing both affected individuals and first-degree relativesof those affected.

We hypothesized that affected individuals and unaf-fected relatives perceive the impact of achondroplasiadifferently and that this would lead to disparate feel-ings on the use of prenatal diagnosis for achondropla-sia. Psychological adaptation to living with a chroniccondition such as achondroplasia is a well-recognizedprocess of seeking to understand, accept and adjust toa health threatening event (Taylor, 1983). The processof adaptation includes finding meaning in the experi-ence of living with the condition, gaining control overone’s condition, and enhancing one’s self-esteem. Pre-vious studies of individuals affected with cystic fibrosishave shown that those affected often view the conditionless severely than their health care providers or fam-ily members (Leung et al., 1997). This likely reflectshealthy adaptation and acceptance. Given these differ-ences, we thought it important to explore the impact ofperception of the condition on decisions about prenatalgenetic testing for achondroplasia.

This research specifically aimed:

(1) To identify the level of awareness and interest inprenatal genetic testing for achondroplasia amongaffected individuals and relatives of those affected.

(2) To identify factors associated with intentions toundergo prenatal genetic testing for achondroplasia.

(3) To determine how individuals or couples withachondroplasia intend to use the results of prenatalgenetic testing.

This information may help health care providers betterunderstand the issues important to the population most

likely to use prenatal genetic testing for achondroplasia.It helps target the needs of those individuals most inter-ested in testing and elucidates education and counselingissues that should be addressed when offering the test.

METHODS

This was a one-time cross-sectional survey administeredunder a National Human Genome Research Instituteprotocol (#96-HG-0123) and approved by the NHGRIInstitutional Review Board. The study was also reviewedand approved by the Medical Advisory Board of theLittle People of America, Inc (LPA). The mailing listwas generated from the membership list of the LPA.Only those members of LPA with achondroplasia andtheir first-degree relatives were included.

Fifteen hundred surveys were distributed in an ini-tial mailing. Seven hundred and fifty were mailed toindividuals identified as having achondroplasia, and theremaining 750 were mailed to parents and siblings ofaffected individuals. Surveys were sorted to avoid distri-bution to more than one member of a given household.One hundred and eighty-two admissible surveys werereturned after the initial mailing, and a second follow-up mailing to non-responders yielded an additional 147surveys. The total number of participants was thus 325,a response rate of 21.6%.

The survey instrument included questions assess-ing participants’ demographic information, awarenessof prenatal genetic testing for achondroplasia, past andpotential future use of the prenatal testing, and past andpotential future reproductive choices. Five questions tar-geted participants’ perception of achondroplasia. Percep-tions of the seriousness of achondroplasia were queriedusing a previously validated question that asked subjectswhether they viewed achondroplasia as a lethal, serious,or not serious disorder (D. Wertz, personal communica-tion). Participants were asked to rank their perceptionof achondroplasia on a scale of 1–10, with one definedas representing traits, like eye color and ten defined asrepresenting disorders, like cancer. Additionally, partic-ipants were asked to choose one word from a list ofseven that most closely matched their view of achon-droplasia. Four-point Likert scales were developed toassess how strongly participants agreed or disagreed thatthere are advantages and disadvantages that come withhaving achondroplasia. Open-ended response fields wereprovided to allow them to comment on specific advan-tages and disadvantages. Four-point Likert scales werealso used to survey the strength of importance partic-ipants place on knowing the three possible diagnosticoutcomes of this testing. Attitudes toward abortion forthe various diagnoses as well as toward abortion in gen-eral were also assessed.

Completed questionnaires were mailed to the datamanagement company Westat, Inc. Responses wereentered into a SAS file and were analysed using theStatistical Package for the Social Sciences 10.0 for Mac-intosh (SPSS Inc., Chicago, IL 2000, USA) and STATA6.0 (Stata Corporation, College Park, TX 1999, USA). In

Copyright 2002 John Wiley & Sons, Ltd. Prenat Diagn 2002; 22: 933–940.

PRENATAL GENETIC TESTING FOR ACHONDROPLASIA 935

preliminary univariate analysis, categorical responses ofaffected individuals and first-degree relatives were com-pared using chi-square tests, while continuous responsesbetween the two groups were compared using t-testsfor independent samples if the data were normally dis-tributed, and the non-parametric Wilcoxon rank-sumtesting if the data were not normally distributed. Sub-sequent multivariate logistical regression modeling wasused to assess the effect of a given variable on impor-tant outcome responses while controlling for the effectsof other covariates.

Some of the demographic variables were dichoto-mized before univariate and multivariate analyses wereperformed. These variables included household income(>$50 000 per year versus less than or equal to $50 000per year), education (college education completed ver-sus not completed), and marital status (currently mar-ried versus not currently married). For the purpose ofmultivariable logistic regression analysis, the perceivedadvantages and disadvantages of having achondroplasiawere dichotomized by collapsing both ‘strongly agree’and ‘somewhat agree’ into one category, and ‘stronglydisagree’ and ‘somewhat disagree’ into another category.The importance of knowing various fetal diagnoses wasalso reduced to a dichotomous outcome variable, with‘extremely important’ and ‘important’ being comparedto ‘somewhat important’ and ‘not at all important.’ Sim-ilarly, one question concerning the participant’s opinionof the severity of achondroplasia was dichotomized into‘not a serious condition’ versus the response of ‘seri-ous condition’ or ‘lethal (deadly) condition.’ Only thoserespondents indicating that they would definitely con-sider or not consider termination of a fetus were utilizedin the univariate and multivariate analysis.

A hierarchical approach was used in selecting thefinal logistic regression model for each outcome. Thisprocess involved first identifying the principal outcomemeasures and corresponding independent predictor vari-ables of greatest scientific interest. The independent vari-ables were then grouped into categories that includeddemographics, opinions about who should have accessto genetic testing, questions concerning intent to usegenetic testing, the desire to know the genetic statusof the fetus, and attitudes toward aborting a fetus with agiven genetic diagnosis. Logistic regression models werethen created from variables within each group for thepurpose of identifying those factors that had the great-est statistical association with each dependent responsevariable. With the exception of the demographic vari-ables, one or two representative variables from eachgroup were then used in selecting the best overall logisticregression model. Because they were generally consid-ered to be the variables of greatest scientific interest,most of the demographic covariates were used whenselecting the final regression model even if they onlyhad a statistically marginal association with the depen-dent variable.

In the final selection process, several possible modelsincorporating numerous combinations of the covariateswere considered, including the forced model, whichincluded all representative variables from each group.Although there is generally no one ‘best’ regression

model for a given set of covariates, unless otherwisenoted, the paper reports what was deemed to be themost parsimonious model for each outcome response,where the most parsimonious model is defined as onethat contains the largest combination of statisticallysignificant covariates (e.g., p-value less than 0.05).

RESULTS

Characteristics of respondents with achondroplasia(ACH) and first-degree relatives of individuals withachondroplasia (FDR) are presented in Table 1. Sex,ethnicity, residential area and employment did not dif-fer significantly among the two groups. Relatives wereslightly older and much more likely to have completedcollege or graduate school (p < 0.05), to report incomesgreater than $50 000 (p < 0.001) and to be married(p < 0.001). Forty-two of the individuals with achon-droplasia, or 22% of those affected, were married toanother affected individual and thus at risk for conceiv-ing a fetus with homozygous achondroplasia.

Respondents in both groups were evenly divided intheir general opinions on abortion (Table 1). Slightlymore relatives than affected individuals answered ‘no’when asked if they thought abortion should be anoption for any couple expecting a child, a differ-ence that approaches significance (p = 0.086). How-ever, multivariate logistical regression analysis revealedthat this difference in attitude toward abortion was notstatistically significant after controlling for the demo-graphic variables of age, marital status, sex and levelof education.

Of the sample population 70% were aware of prenatalgenetic testing for achondroplasia. A majority (65% ofaffected individuals and 56% of relatives) of those awareof the testing reported the Little People of America,Inc. as the source of their information. Other sources,in descending order of frequency, included health careproviders, media, family members and friends. Only 13affected individuals and one relative reported past useof the prenatal genetic testing and all indicated they feltthis was the right decision at the time.

Reproductive history and intentions ofindividuals with achondroplasia andfirst-degree relatives

We assessed both the reproductive history of affectedindividuals and relatives, as well as their future repro-ductive plans. Results are presented in Table 2. While amuch greater percentage of relatives had living biologi-cal children, each group reported similar frequencies ofaffected and unaffected children. Because many individ-uals had both children with achondroplasia and of aver-age stature, these were not mutually exclusive subsetsof the total number reporting having living biologicalchildren. In addition, more affected individuals than rel-atives reported interest in having biological children oradopting children in the future.



Table 1—Characteristics of respondents with achondroplasia (ACH) and parents and siblingsof individuals with achondroplasia (first-degree relatives, FDR)

ACH (n = 189) FDR (n = 136)

Age†, mean (range) in years 40.5 (19–89) 43.5 (20–84)Percentage under 29 21 5Percentage 30–39 24 29Percentage 40–49 35 46Percentage over 49 20 20

Sex, percentage female 67 76Ethnicity, percentage Caucasian 91 94Marital status∗, percentage married 49 89Education level†, percentage completingcollege or graduate school

46 59

Employment, percentage employed full-time 54 48Income∗, percentage greater than $50 000 31 73Residential area, percentage

Rural 14 17Small city/town 44 40Major metropolitan area 42 43

General support for abortionPercentage Yes 38 39Percentage No 38 47Percentage Unsure 23 14

∗ Significantly different at p < 0.001, respondents with ACH compared to first-degree relatives.† Significantly different at p < 0.05, respondents with ACH compared to first-degree relatives.

Table 2—Reproductive history and future plans of individuals with achondroplasia andfirst-degree relatives

ACH (n = 189) FDR (n = 136)Per cent yes (n) Per cent yes (n)

Have living biological children 39 (73) 92 (125)with achondroplasia 26 (50) 8 (119)of average stature 22 (41) 80 (109)

Planning to have children 12 (22) 6 (8)Unsure of plans to have children 12 (23) 6 (8)Would use prenatal test for ACH if pregnant∗ 62 (116) 28 (38)Had miscarriage/stillbirth/neonatal death 18 (34) 37 (50)

due to homozygous achondroplasia 6 (11) 0 (0)Have adopted children 13 (25) 4 (3)

with achondroplasia 7 (14) 2 (2)with other form of dwarfism 4 (7) 0 (0)of average stature 4 (7) 2 (2)

Plan to adopt children 8 (15) 2 (3)with achondroplasia (yes or unsure) 7 (14) 2 (2)with other form of dwarfism (yes or unsure) 5 (10) 1 (1)

Considering adopting children 30 (56) 12 (16)

∗ Significant chi-square test (OR = 6.91, p < 0.001), comparing affected individuals and relatives.

Perception of the condition

Five questions of the survey instrument assessed percep-tion of the condition. Participants were asked to placeachondroplasia on a spectrum ranging from trait (1) todisorder (10). Mean responses (± standard deviation)were found to be 5.26 ± 2.69 for affected individualsand 5.70 ± 2.73 for relatives and were not significantlydifferent. Participants were then asked to choose oneword from a list to describe achondroplasia. Results fromthis question did not differ significantly among affectedindividuals and relatives. Over a third of each groupchose the word ‘condition’ to describe achondroplasia.

‘Difference’ and ‘disability’ were the next most fre-quently chosen responses.

First-degree relatives were 4.01 (95% CI = 2.09,7.72) times more likely than those affected tostate that achondroplasia is a serious or deadlycondition. This analysis controlled for demographicvariables and opinions about whether couples notat risk for conceiving a child with homozygousachondroplasia should have access to prenatal testingfor achondroplasia. Affected individuals were 2.06 (95%CI = 1.19, 3.57) times more likely than relatives toagree somewhat or strongly that there are advantagesthat come with having achondroplasia. This analysis



controlled for demographic variables, the desire toknow if the fetus has achondroplasia, and opinionsabout whether couples not at risk for conceiving achild with homozygous achondroplasia should haveaccess to prenatal testing for achondroplasia. Almostall participants (89% of affected individuals and 99%of relatives) agreed with the statement that there aredisadvantages that come with having achondroplasia aswell. Only one relative even somewhat disagreed withthis statement, as compared to 18 affected individuals(unadjusted OR = 14.36, 95% CI = 1.89, 108.93).However, the number of participants disagreeing thatthere are disadvantages to having achondroplasia wastoo small to allow for further multivariate analysis ofthe two groups.

Attitudes of affected individuals andrelatives toward prenatal diagnosisoutcomes

Participants were asked to rate how important it wouldbe to know the diagnoses of homozygous achondropla-sia, heterozygous achondroplasia and average statureprenatally. Responses were indicated on a Likert scaleand the results are presented in Figure 1. Three-quartersof respondents in both groups indicated that it wouldbe extremely important or important to know the diag-nosis of the lethal form of achondroplasia prenatally.This trend was reversed for both the diagnoses of het-erozygous achondroplasia and average stature. Affectedindividuals were more likely than relatives to indicatethat it was important to know the diagnosis of averagestature prenatally.

Multiple logistic regression was performed in order todetermine those characteristics most significantly asso-ciated with the importance of knowing the diagno-sis of heterozygous achondroplasia or average stature.

50

26

1311

1619

27

38

1114

23

52

0

10

20

30

40

50

60

%

HomozygousAchondroplasia

HeterozygousAchondroplasia

Average Stature

Extremely

Important

Somewhat

Not Important

Figure 1—Importance of knowing the diagnoses of homozygousachondroplasia, heterozygous achondroplasia and average stature pre-natally (n = 325). Univariate analysis supported statistical differencesamong affected individuals and relatives only in regards to the impor-tance placed on knowing the diagnosis of average stature (p < 0.054)

Affected status, sex, age, marital status, education level,income, general views on abortion, and perception of thecondition were considered in this analysis. Results of themost parsimonious models are presented in Table 3.

Attitudes of affected individuals andrelatives toward abortion based on prenataldiagnosis results

Participants in both groups were evenly divided whenasked if they would ever consider having an abor-tion because the fetus had homozygous achondroplasia(Figure 2). Responses to this question were correlatedwith general support for abortion, with those in sup-port of abortion ten times more likely to express interestin terminating fetuses with homozygous achondroplasiaafter controlling for being affected with achondropla-sia, age, sex, education status and marital status (OR =10.05, 95% CI = 5.32, 18.97). None of these demo-graphic covariates were found to significantly predictsupport for aborting a fetus with homozygous achon-droplasia. Participants were overwhelmingly not willingto consider termination of a fetus based on the diagnosisof either achondroplasia or average stature, regardless ofviews on abortion.

Views on abortion in general did appear to contributesignificantly to other attitudes assessed in the survey.Those in support of abortion were 3.4 times more likelyto express interest in using the testing if pregnant aftercontrolling for being affected with achondroplasia, age,sex, educational status and marital status (95% CI =1.75, 6.77). Of the above listed demographic covariates,only age was found to statistically predict use of thegenetic testing for achondroplasia if pregnant, with anodds ratio of 1.05 for each year increase in age (95%CI = 1.02, 1.09). Those in support of abortion were alsomore likely to indicate it was important or extremely

40 41

19

5

86

83

90

6

0

10

20

30

40

50

60

70

80

90

100

%

HomozygousAchondroplasia

HeterozygousAchondroplasia

Average Stature

Yes

No

Unsure

Figure 2—Consideration of termination of fetus based on prenataldiagnosis outcome (n = 325). (Differences among respondents withachondroplasia and first-degree relatives were not significant)



Table 3—Characteristics related to the importance of knowing the prenatal diagnosis of heterozygousachondroplasia and average stature: stepwise multiple logistic regression

Important toknow

achondroplasia

Important toknow average

stature

Characteristics Odds ratio (p-value) Odds ratio (p-value)Affected with achondroplasia 2.33 (0.012)†

Support abortion in general 4.23 (0.000)∗ 2.99 (0.007)∗Completed less than a college degree 2.65 (0.002)∗ 2.47 (0.025)†

View ACH as more of a disorder than a trait 1.21 (0.008)∗Consider ACH a serious condition 2.43 (0.007)∗Disagree there are advantages to having ACH 2.09 (0.025)† 2.10 (0.023)†

∗ Significant chi-square test, p < 0.01.† Significant chi-square test p < 0.05.

important to know any of the three potential prenataldiagnosis outcomes.

DISCUSSION

This study is an initial assessment of attitudes towardprenatal genetic testing for achondroplasia held byaffected individuals and relatives of those affected. Ahigh percentage of our study cohort was aware of thisprenatal genetic testing at the time of the survey. Notsurprisingly, the majority of those aware of the testingreported learning about it through the Little People ofAmerica, Inc. organization, a national support group forshort statured individuals. LPA has issued statementsregarding the discovery of genetic alterations responsiblefor achondroplasia and the subsequent development ofprenatal testing for the condition (Ricker, 1995; LittlePeople of America, 1996). In addition, respondents wererecruited through the LPA. This sample is thus likelyto include individuals who are more aware of andinterested in new genetic technologies. It is also possiblethat awareness of the genetic testing for achondroplasiamotivated respondents to complete the survey.

This study, however, suggests that actual uptake ofprenatal genetic testing for achondroplasia has been lessthan might have been anticipated. Extrapolation fromcommunication with six of the commercial laboratoriescurrently offering the testing prenatally suggested thataround 100 tests were performed in the proceedingyear and that the majority were performed subsequentto ultrasound findings that suggested achondroplasia.Whether or not this testing will be increasingly used inthe future to diagnose the lethal form of achondroplasia,achondroplasia or average stature is unknown.

Our data do indicate that both affected individualsand relatives are interested in using the testing shouldthey become pregnant in the future. However, it isimportant to note that research on offering genetic testingboth for individual risk assessment (e.g., Huntington’sdisease and cancer susceptibility) and prenatal diagnosis(e.g., cystic fibrosis) indicates that interest in usinggenetic testing is often greater than actual use of suchtests (Wiggins et al., 1992; Jedlicka-Kohler et al., 1994;Biesecker et al., 2000). Speculation about future use of

testing also seemed to exceed the proportion of bothaffected individuals and relatives contemplating futurepregnancies.

We also sought to investigate factors that might pre-dict individual use of this testing. The low frequency ofprior use of prenatal genetic testing for achondroplasia,coupled with the relatively recent development of thetesting, suggests that most past reproductive decisionshave been made without consideration of this clinicaltool. The proportion of affected individuals who hadadopted or were open to adoption (51%) was equiva-lent to the proportion who had or were planning to havebiological children (51%). This balance was not seen inthe cohort of relatives. We surmise that concern aboutthe risk of conceiving a child with homozygous achon-droplasia likely contributed to some of this differencein the responses from the two cohorts concerning pastreproductive decisions.

In addition to facing discrepant risks and making dif-ferent reproductive decisions, we also found that affectedindividuals shared perceptions of the condition that weresignificantly different from those held by first-degree rel-atives. Four of the five questions used to survey percep-tion of the condition suggested that affected individualsview the condition as closer to a trait than a disorder,as less serious, as coming with more advantages andas having fewer disadvantages, when compared to theresponses of relatives of those affected. This differencein perception was an important observation both becauseit suggests that these individuals with achondroplasiahave undergone psychological adaptation to living withthe condition and because it seemed to contribute to theimportance respondents placed on knowing the variousdiagnoses prenatally.

The importance participants placed on knowing thethree possible outcomes of this prenatal genetic testingand their willingness to consider termination based onthose outcomes support the assumption that they weremost interested in avoiding the lethal form of achon-droplasia. This information would be most germane tothe 22% of affected individuals surveyed who are mar-ried to another affected person. However, those affectedindividuals not currently married to another affectedindividual may also have been contemplating their riskfor conceiving such a child in the future. Relatives mayhave been speculating about the importance of prenatal



diagnosis for their children and thus future grandchil-dren. The understanding that they were not personallyat risk for the lethal form of achondroplasia may be afurther reason why relatives were much less likely to beinterested in using this testing.

However, there was some interest in knowing thediagnoses of achondroplasia and average stature prena-tally. Support for abortion in general had the highest cor-relation with considering it important to know either ofthese diagnoses. Previous literature has shown that thosewho use prenatal diagnosis are more likely to supportabortion as a viable reproductive option (Green et al.,1993; Julian-Reynier et al., 1994; Press and Browner,1998). Respondents did not indicate that they wouldutilize abortion for either of these two outcomes; how-ever, it is conceivable that those not in favor of abortionwould indicate that it is not at all important to knowthese diagnoses if they do not see any other motivationfor pursuing prenatal diagnosis. Those with less than acollege degree were also more likely to deem it impor-tant to know these diagnoses prenatally. We conjecturethat this may be due to a greater tolerance of ambiguityamong people with higher formal education (Furnhamand Ribchester, 1995).

Lastly, those who view achondroplasia as a seriouscondition or who do not agree that it comes withadvantages were more likely to find it important to knowthe diagnoses of achondroplasia and average stature.This may hint at a preference for unaffected childrenbut one that is not strong enough to consider terminationof affected fetuses. Affected individuals were also morelikely to want to know the diagnosis of average statureprenatally. Because we did not survey the preference ofaffected individuals to have similarly affected children,we can only speculate that it might be preferable forthose affected to have children like themselves, but notof great enough importance to warrant termination ofunaffected fetuses.

The main limitation of this study is the low responserate. Respondents do not necessarily offer a representa-tive sample of individuals with achondroplasia or theirrelatives, or even of individuals with achondroplasia andrelatives who belong to the Little People of America,Inc. By only surveying those individuals from the LPAdatabase to begin with, we introduced another limita-tion in that this study is inherently biased toward peoplemore likely to have access to information about achon-droplasia and access to health care services and options.In addition, over 90% of participants were Caucasian.Since achondroplasia likely occurs in all ethnic groups,respondents represent a subset of one ethnic perspective.

Larger and more inclusive studies need to be doneto replicate and expand our findings. However, thisinitial insight into an area that has not been previ-ously studied may serve as a window into the views ofthe achondroplasia community. The data provide healthcare practitioners with preliminary information aboutinterest in prenatal genetic testing for achondroplasia.Providers should continue to address concern about therisk for homozygous achondroplasia in affected couplesand should offer this testing as a possible alternative todelivering a stillborn or critically ill newborn. Providers

should not assume that affected individuals prefer tohave either affected or unaffected children and shouldexplore personal views on abortion. They should con-sider a client’s perception of achondroplasia as havingan effect on prenatal diagnosis decisions, and they mightassume individuals with achondroplasia have a morepositive view of the condition compared to relatives orthe general public.

ACKNOWLEDGEMENTS

This study was conducted within and funded bythe Medical Genetics Branch of the National HumanGenome Research Institute Intramural Program underIRB Protocol #96-HG-0123. We would like to thankAbby Irwin, Anya Guyer and Andrea Seltzer for helpwith the development of this study. We would also liketo express gratitude to Cathy Ann Grundmayer and Shel-ley Niwa of Westat, Inc for their assistance with datamanagement.

REFERENCES

Ablon J. 1984. Little people in America: the social dimensions ofdwarfism. Praeger: New York.

Bellus GA, Hefferon TW, Oritz de Luna RI, et al. 1995. Achon-droplasia is defined by recurrent G380R mutations of FGFR3 . AmJ Human Genet 56: 368–373.

Biesecker BB, Ishibe N, Hadley DW, et al. 2000. Psychosocialfactors predicting BRCA1/BRCA2 testing decisions in membersof hereditary breast and ovarian cancer families. Am J Med Genet93: 257–263.

Castiglia PT. 1996. Achondroplasia. J Pediatric Health Care 10:180–182.

Committee on Genetics. 1995. Health supervision for children withachondroplasia. Pediatrics 95: 443–451.

Furnham A, Ribchester T. 1995. Tolerance of ambiguity: a reviewof the concept, its measurement and applications. Currn Psych:Develop, Learn, Person, Soc 14: 179–100.

Gorlin RJ, Cohen MM, Levin LS, et al. 1990. Syndromes of the headand neck. Oxford University Press: New York.

Green JM, Snowdon C, Statham H, et al. 1993. Pregnant women’sattitudes to abortion and prenatal screening. J Reprod Infant Psych11: 31–39.

Jedlicka-Kohler I, Gotz M, Eichler I, et al. 1994. Utilization ofprenatal diagnosis for cystic fibrosis over the past seven years.Pediatrics 94: 13–16.

Julian-Reynier C, Macquart-Moulin G, Moatti JP, et al. 1994. Rea-sons for women’s non-uptake of amniocentesis. Prenat Diagn 14:859–864.

Leung SS, Steinbeck KS, Morris SL, et al. 1997. Chronic illnessperception in adolescence: implications for the doctor–patientrelationship. J Paediatrics Child Health 33: 107–112.

Little People of America, Inc. 1996. Position statement on genetic dis-coveries in dwarfism. http://www.lpaonline.org/resources faq.html[April 2000].

Mettler G, Fraser FC. 2000. Recurrence risk for sibs of children with‘sporadic’ achondroplasia. Am J Med Genet 90: 250–251.

Murdock JL. 1970. Achondroplasia—a genetic and statistical survey.Annals Human Genet 33: 227–244.

Press N, Browner CH. 1998. Characteristics of women who refusean offer of prenatal diagnosis: data from the California maternalserum alpha fetoprotein blood test experience. Am J Med Genet 78:433–445.

Ricker RE. 1995. Do we really want this? Little People of America,Inc. comes to terms with genetic testing. http://ww2.shore.net/∼dkennedy/dwarfism ricker.html [April 2000].



Rousseau F, Bonaventure J, Le Merrer M, et al. 1994. Mutationsin the gene encoding fibroblast growth factor receptor-3 inachondroplasia. Nature 371: 252–253.

Shiang R, Thompson LM, Zhu YZ, et al. 1994. Mutations in thetransmembrane domain of FGFR3 cause the most common geneticform of dwarfism, achondroplasia. Cell 78: 335–342.

Taylor SE. 1983. Adjustment to threatening events: a theory ofcognitive adaptation. Am Psych 1161–1173.

Webster MK, Donoghue DJ. 1996. Constitutive activation offibroblast growth factor receptor 3 by the transmembrane domainpoint mutation found in achondroplasia. EMBO J 15: 520–527.

Wiggins S, Whyte P, Haggins M. 1992. The psychological conse-quences of predictive testing for Huntington disease. New Engl JMed 327: 1401–1405.


issues surrounding prenatal genetic testing for achondroplasia

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