American Journal of Medical Genetics 34:552-554 (1989)

Decisions Following the Intrauterine Diagnosis of Sex Chromosome Aneuploidy Arthur Robinson, Bruce G. Bender, and Mary G. Linden Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine (A.R. , B.G.B., M.G.L.), Department of Pediatrics and Department of Biochemistry, Biophysics and Genetics (A.R .), and Department of Psychiatry (B.G.B.), University of Colorado School of Medicine, Denver

This is a report of 327 phone calls to our center concerning the intrauterine diagnosis of sex chromosome abnormalities (SCA). The first author (A.R.) responded to each by counsel- ing either the parents or the referring profes- sional. Sixty-two percent continued the preg- nancy. When the parents were counseled directly, the percentage continuing the preg- nancy was significantly higher than when the information was transmitted through the pro- fessionals. Our results are different from most reports in these situations, and suggest that well-informed couples, counseled by geneti- cists, are more likely to continue these preg- nancies. The possible occurrence of SCA should be considered in preamniocentesis counseling.

KEY WORDS: sex chromosome abnormal- ities, parental decisions, ge- netic counseling

INTRODUCTION Since the late 1960s prenatal diagnosis has been uti-

lized increasingly to rule out aneuploidy, in particular trisomy 21 [Henry et al., 19781. When autosomal aneu- ploidy is diagnosed the prognosis is generally poor and parents usually decide to interrupt such pregnancies [Verp et al., 19881. On the other hand, the intrauterine diagnosis of sex chromosome aneuploidy (SCA), occur- ring in about 1 in 300 cases, has presented a more difficult dilemma since the prognosis of these conditions is less predictable and there may be a wide range from near normality to moderately severe handicap. On noti- fication of a diagnosis of sex chromosome abnormality prenatally, parents are faced with a particularly agoniz- ing decision regarding possible termination. Hence the

Received for publication March 6,1989; revision received June 7, 1989.

Address reprint requests to Arthur Robinson, M.D., National Jewish Center of Immunology and Respiratory Medicine, 1400 Jackson Street, Denver, CO 80206.

0 1989 Alan R. Liss, Inc.

critical importance of objective data about the clinical outcome in the various types of SCA has become evident, and only recently has the natural history of these condi- tions become clear [Ratcliffe and Paul, 19861.

METHODS The Denver Family Development Study, which

started in 1964 and is still in progress [Robinson et al., 19861, is a longitudinal prospective study of growth and development of a group of newborn infants with SCA unselected as to phenotype. This study has produced numerous contributions to the medical literature. Be- cause of this the principal investigator (A.R.) receives many phone calls from physicians and patients through- out the United States who are faced with the dilemma of what to do about the intrauterine diagnosis of sex chro- mosome abnormalities. This is a report of 327 phone calls with a follow-up as to action taken for each karyo- type. In general, one of 2 procedures takes place:

1. The patient’s physician calls and asks for our opin- ion as to the prognosis.

2. The patient’s physician or counselor calls and asks if the parents can call directly, and then they telephone.

At the time of consulting with the inquiring physi- cian, genetic counselor, or parent, a request is made that we be notified of the final decision as to continuation of the pregnancy. If we have not heard from them in about 6 weeks, we call to learn of the decision.

RESULTS Of 263 amniocenteses in which SCA was present in all

the amniocytes examined, 62% continued the pregnancy (Table I). It is of interest to note that the lowest percent- age of pregnancies continued were 45,X and 47,XXY, the 2 chromosome abnormalities that included infer- tility in the prognosis.

Among the 64 sex chromosome mosaics, 82% of the pregnancies were continued (Table II), which mirrors the fact that, in general, in mosaics, one of whose cell lines has a normal karyotype, the phenotype tends to be milder [Robinson et al., 19861. When the information was given by the first author (A.R.) directly to parents, 75% continued the pregnancy. When the information

Intrauterine Diagnosis of SCA: Parental Decisions 553

TABLE 111. Effect of Personal Contact TABLE I. Parental Decision-Non-Mosaics

Karyotype Keep Terminate Total % kept

XYY 51 24 75 68 45 ,x 5 4 9 56 xxx 66 36 102 65 XXY 41 34 75 55 XXYY 1 1 2 Total 164 99 263 62

was provided to the other professionals for transmission to their patients, 59% continued the pregnancy (Table 111). This was a significant difference (P<0.005).

DISCUSSION There is no question that these data are highly biased

by the fact that the parents involved are a select group. They were predominantly white, educated people, 85% professionals, who had already read much of the current literature. In addition, it is possible that the only ones who called were those who were ambivalent about what course to pursue. This may be why we received so few calls about 45,X fetuses who have a high probability of gross abnormality.

The points that were made in answer to the phone call which differed in varying degree from what the parents had been previously told were-

1. Mental retardation is not a characteristic finding, although the I.&. is likely to be lower than that of sibs. The difference between SCA and Down syndrome in this regard is commented on. The prognosis for I.&. is in general poorest for 47,XXX females.

2. With the exception of Ullrich-Turner syndrome, SCA individuals are not malformed or severely hand- icapped. Unlike individuals with Down syndrome, their usual phenotype does not make them stand out.

3. The increased frequency of speech delay, school problems, and difficulty with peer relations is men- tioned.

4. The children often have a poor self-image and may be emotionally immature.

5. It is stressed that with the exception of infertility in 45,X and infertility and possible gynecomastia in 47,XXY individuals, none of the children with these karyotypes have problems that are unique. Hence their management is no different from that of eukaryotic indi-

TABLE 11. Parental Decision-Mosaics

Karyot ype

XIXX XYIXXY x x / x x x XiXY XYiXYY xixxx XIXXiXXX XYiXXYY XIXYY Total

Keep

1 4 10 9 9 6 1 2 1 1

53

Terminate Total

1 2 1 3 1 3 0 0 0

11

15 12 10 12

7 4 2 1 1

64

% kept

93 83 90 75 86 25

100 100 100

82

Total Keep Terminate % kept ~ ~~

Personal 155 116 39 75 Counselor 163 96 67 59

viduals with similar problems. Recent advances in the endocrine management of Ullrich-Turner syndrome are also discussed for 45,X fetuses [Rosenfeld et al., 19881.

6. There is no substantiated evidence for an increase in abnormal sexual activity such as homosexuality, transvestism, or transsexualism.

7. The great variability of the phenotype is noted; and the florid depiction of these conditions described in the literature represents only one end of the spectrum.

8. Our general hypothesis that these individuals have difficulty in adapting to the stresses of growing up is mentioned, as well as our evidence that those coming from stable and supportive environments do better [Bender et al., 19871.

9. Mosaic individuals in general have a better prog- nosis and fewer problems, although they cover a spec- trum from the complete phenotype to the normal. The 45,Xl46,XY mosaic is a special category that is dis- cussed in detail when appropriate [Wheeler et al., 19881.

The literature suggests that in practice, when SCA is diagnosed in utero, termination is usually requested, even for sex chromosome mosaics [Holmes-Siedl et al., 1987; Nielsen and Pelsen, 1987; Anonymous, 1979; Benn et al., 1985; Verp et al., 19881. Verp et al. [19881 have collected data on the results of 235 amniocenteses from 24 published studies (Table IV). Even though mo- saics were not separated out, only 33% of the pregnan- cies were continued. It is again notable that 45,X and 47,XXY fetuses had the highest number of termina- tions. This suggests that the prospect of infertility is a strong factor in decision making [Borelli et al., 19841. The difference between these collected data and our results (Table V) is striking.

Undoubtedly, the parents’ reaction to an intrauterine diagnosis of SCA will vary with many factors: their fertility, education, expectations, emotional stability, their ages, and their financial resources. However, an extremely important factor is what they are told by counselors, many of whom are not clinical geneticists and who get their information from the available text- books [Holmes-Siedl et al., 19871. Verp et al. [1988] report their own results on a smaller group of parents of

TABLE IV. Pregnancy Outcomes @CAI Collected Amniocentesis*

~ ~ ~~

Karyotype Keep Terminate Total % kept

XYY 13 17 30 43 45,X (and 12 35 47 26

xxx 28 35 6 3 44 XXY 24 71 95 25 Total 77 158 235 33

mosaics)

*Verp et al. [19881.

554 Robinson et al.

TABLE V. 70 SCA Kept: Denver vs. Collected Results*

%

Karyotype Denver Collected

XYY 4 5 , x xxx XXY Total

68 56 65 55 62

43 26 44 25 33

*Collected results from Verp e t al. [19881.

SCA fetuses, all of whom were counseled by a geneticist. Ten of 17 continued the pregnancy, a proportion similar to ours. Our own data further confirms the fact that counseling by a geneticist familiar with these syn- dromes makes a difference (Table 111). It has been sug- gested, indeed, that in counseling prior to prenatal diag- nosis, sex chromosome abnormalities as a potential problem should be mentioned, and that such parents are less likely to terminate an SCA pregnancy.

Several ongoing prospective surveys [Ratcliffe and Paul, 19861 are depicting SCA children as having ex- tremely variable phenotypes with only a relatively small minority having the very serious prognosis that represents one extreme of the spectrum. Our own results and those reported from Denmark [Nielsen and Pelsen, 19871 andEngland [Holmes-Siedl et al., 19871 are begin- ning to indicate that well-informed parents are more likely to continue these pregnancies. It is to be hoped that couples will more frequently be counselled by a clinical geneticist when these diagnoses are made and that the possible occurrence of SCA be considered in preamniocentesis counseling.

ACKNOWLEDGMENTS This study was supported, in part, by NIH grant

5R01-HD10032 from the Public Health Service and by The Genetics Foundation.

Gratitude is expressed to Jean Clyne for her assis- tance in collecting the data.

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Borelli JB, Bender BG, Puck MH, Salbenblatt JA, Robinson A (1984): The meaning of early knowledge of a child‘s infertility in families with 47,XXY and 45,X children. Child Psychiatry Hum Dev 14:215-221.

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