American Journal of Medical Genetics 80:330–334 (1998)
Low Rates of Pregnancy Termination for
Prenatally Diagnosed Klinefelter Syndrome and
Other Sex Chromosome Polysomies
Dieter Meschede,1 Frank Louwen,2 Irmgard Nippert,1 Wolfgang Holzgreve,2 Peter Miny,1 and
Jürgen Horst1*
1
Institut für Humangenetik, Westfälische Wilhelms-Universität, Münster, Germany
2
Universitäts-Frauenklinik, Westfälische Wilhelms-Universität, Münster, Germany
Over the past 9 years we counseled 55
couples whose unborn child was found to
carry a sex chromosome polysomy. We per-
formed a survey of postcounseling parental
decisions about continuation or termina-
tion of these pregnancies. Of the 55 embryos
or fetuses, 23 had the karyotype 47,XXY, 10
had 47,XYY, and 12 had 47,XXX. In addition,
there were 10 instances of true mosaicism,
i.e. 47,XXY/46,XY (n = 5), 47,XYY/46,XY (n = 2),
or 47,XXX/46,XX (n = 3). Mean gestational
age (± standard deviation) at diagnosis was
18.3 ± 3.0 weeks. After comprehensive ge-
netic counseling 48 (87.3%) of these preg-
nancies were carried to term. In seven cases
(12.7%) the parents elected a pregnancy ter-
mination. Two of 31 pregnancies (6.5%) pri-
marily ascertained at our center were
aborted, whereas amongst the 24 referred
cases, 5 couples (20.8%) opted for a termina-
tion. The mean gestational age of the termi-
nated pregnancies was 19.7 weeks. The
overall termination rate of 12.7% appears
low in comparison with literature data.
Most reports from other institutions present
termination rates between 32 and 66%. The
reason for the low rate of induced abortions
in our study cohort is not clear. Cultural dif-
ferences in parental perception of sex chro-
mosomal polysomies may be of importance,
and peculiarities of genetic counseling at
our institution could also play a role. Al-
though counseling was nondirective, we did
put emphasis on providing prospective par-
Current address of W.H. is Universitäts-Frauenklinik, Basel,
Switzerland.
Current address of P.M. is Basler Kinderspital, Basel, Switzer-
land.
*Correspondence to: Prof. Jürgen Horst, Institut für Human-
genetik der Universität, Vesaliusweg 12-14, D-48149 Münster,
Germany. E-mail: horstj@uni-muenster.de
Received 11 December 1997; Accepted 12 February 1998
© 1998 Wiley-Liss, Inc.
ents with information from unbiased follow-
up studies of children with Klinefelter syn-
drome and other sex chromosome polyso-
mies. Am. J. Med. Genet. 80:330–334, 1998.
© 1998 Wiley-Liss, Inc.
KEY WORDS: prenatal diagnosis; Klinefel-
ter syndrome; 47,XXX female;
47,XYY syndrome; genetic
counseling; pregnancy termi-
nation
INTRODUCTION
Because of the widespread use of amniocentesis and
chorionic villus sampling [Nippert et al., 1997], the pre-
natal recognition of sex chromosome anomalies (SCA)
has become increasingly common [Robinson et al.,
1992]. The prognostic significance of such a prenatal
diagnosis depends on the type of SCA present. Rare
structural aberrations disregarded, sex chromosome
anomalies can be grouped into two categories. On one
hand, there is Ullrich-Turner syndrome (UTS, karyo-
type mostly 45,X) that has an 80 to 90% prenatal loss
rate [Hook, 1983] and can be associated with signifi-
cant postnatal morbidity caused by cardiovascular de-
fects, ovarian dysfunction, development problems, and
short stature [Hall and Gilchrist, 1990]. On the other
hand, the 47,XXX and 47,XYY syndromes have a natu-
ral prenatal course not significantly different from
chromosomally normal pregnancies. The spontaneous
loss rate in Klinefelter syndrome (47,XXY) is somewhat
increased, but most such pregnancies survive to term.
Postnatally, mild academic problems are common in all
three types of sex chromosome polysomy (XXX, XXY,
XYY) [Bender et al., 1993, Rovet et al., 1995], and in-
fertility is to be expected among men with Klinefelter
syndrome. Otherwise, the postnatal development of in-
dividuals with 47,XXY, 47,XYY, and 47,XXX karyo-
types is largely normal [Robinson et al., 1990]. This
relatively benign picture of the sex chromosome poly-
somies has emerged only when long-term follow-up
studies of affected individuals ascertained in an unbi-
ased manner became available [Evans et al., 1990].

Although the chances for a livebirth in prenatally
diagnosed UTS are poor, most gestations with sex chro-
mosome polysomy will survive to term. Given that no
major malformations or severe mental handicaps are to
be expected, the prospective parents are confronted
with a difficult decision—should they terminate the
pregnancy or keep it despite the presence of a sex chro-
mosomal abnormality [Anonymous; 1979]? Few data
are available on the outcome and the determinants of
this decision-making process. Studies from Europe
[Holmes-Siedle et al., 1987; Abramsky and Chapple,
1997] and the United States [Tannenbaum et al., 1986;
Verp et al., 1988; Robinson et al., 1989] suggest that a
major proportion of such gestations are terminated.
Over the past 9 years we have counseled 55 couples
whose embryo or fetus was diagnosed to carry a sex
chromosome polysomy. We performed a retrospective
analysis of the postcounseling outcome of these gesta-
tions.
METHODS
All cases for which over the past 9 years a prenatal
diagnosis of sex chromosomes polysomy (karyotypes
47,XXY, 47,XYY, or 47,XXX in nonmosaic or mosaic
state) was made at our laboratory were identified
through searching a database established in 1989. We
also considered cases in which the cytogenetic diagno-
sis had been made in outward institutions and the pa-
tients were referred for post-test counseling only. The
diagnosis of sex chromosome polysomy was verified
from the original patient charts and laboratory sheets.
Cases of presumed pseudomosaicism because of culture
artifact or confined placental mosaicism were excluded.
Thirty-one cases for which the prenatal diagnostic
studies including chromosome analysis had been per-
formed at our hospital and 24 cases referred from out-
ward institutions remained. The postcounseling course
and outcome of most pregnancies were documented in
the patient charts. Otherwise, we contacted the obste-
trician caring for the patient and inquired about preg-
nancy outcome.
Most patients who had chorionic villus sampling
(CVS) or amniocentesis at our institution had under-
gone formal genetic counseling before the invasive pro-
cedure. Counseling after the diagnosis of a sex chromo-
some polysomy was performed by an MD geneticist in
the Institute of Human Genetics (53 cases) or at the
Women’s Hospital by an obstetrician trained in medi-
cal genetics (1 case). One patient who underwent CVS
and whose fetus was found to have a 47,XXY karyotype
did not wish to travel to our hospital again and was
counseled by telephone. The post-test genetic counsel-
ing session took 1 to 2 hours, and with few exceptions
both partners were present.
The type of chromosomal abnormality found was ex-
plained, and an extensive discussion of the pre- and
postnatal natural course of the condition ensued. The
prognosis for psychomotor development of children
with sex chromosomal polysomy was explained in de-
tail as was hypogonadism in cases of Klinefelter syn-
drome. Current and possible future treatment options
were discussed. It was offered to establish contact with
Prenatally Diagnosed Klinefelter Syndrome 331
parents who already have a child with the SCA under
discussion, and in cases of Klinefelter syndrome con-
tact with a pediatric endocrinologist and a patient sup-
port group was also offered. A detailed high-resolution
ultrasound scan was routinely recommended to ex-
clude major structural malformations.
RESULTS
Fifty-five pregnancies with the diagnosis of a sex
chromosome polysomy were included into our analysis.
One additional case of prenatally diagnosed Klinefelter
syndrome was not considered as we were unable to
obtain follow-up information. We also excluded four
cases (47,XXY, 47,XXY/46,XY, 47,XYY, and 47,XXX)
that were ascertained later than the 24th week of ges-
tation, the limit for an induced abortion in Germany.
Of the analysed cases, 53 were a singleton, one a twin,
and one a triplet pregnancy. In the latter two, only one
fetus was found to carry an SCA, whereas the others
were unaffected. The diagnosis was established until
the end of the 14th postmenstrual week in nine cases
and between the 15th and the 24th week in 46 cases.
The mean (± standard deviation) gestational age at the
time of diagnosis was 18.3 ± 3.0 weeks (median 19
weeks, span 12 to 23 weeks). The indications for inva-
sive prenatal diagnosis were: advanced maternal age
(35), abnormal or borderline ultrasound findings (6),
anxiety (5), increased risk for Down syndrome on triple
marker screening (4), previous abnormal pregnancy
(2), and risk for X-linked hydrocephalus (1). In two
cases referred from outside institutions the indication
for the prenatal test was not documented. Sixteen pa-
tients had a first trimester chorionic villus biopsy and
39 an amniocentesis. A postnatal control of the karyo-
type was carried out in 15 children. In 14 cases includ-
ing four mosaics the prenatal cytogenetic diagnosis was
confirmed. One case of prenatally diagnosed nonmosaic
47,XXY showed a low-level 47,XXY[28]/46,XY[2] mo-
saic at postnatal karyotyping of blood lymphocytes.
Table I summarizes the cytogenetic findings and the
postdiagnosis course of the 55 analysed gestations with
sex chromosome polysomy. Case details are given in
Table II. All but seven pregnancies were carried to
term. Among them were six cases with abnormalities
on ultrasound scanning: nuchal edema (cases 21, 35,
and 52), dilated renal calices (case 32), hydrothorax
(case 35), and bilateral talipes equinovarus (case 15).
TABLE I. Cytogenetic Diagnoses and Postcounseling Course of
55 Pregnancies With Sex Chromosome Polysomy
Number Carried
Cytogenetic diagnosis of cases Terminated to term
47,XXY 23 4 19
47,XXY/46,XYa 5 0 5
47,XYY 10 1 9
47,XYY/46,XYa 2 0 2
47,XXX 12 2 10
47,XXX/46,XXa 3 0 3
All cases 55 7 (12.7%) 48 (87.3%)
a
Cases with pseudomosaicism were excluded. The aneuploid cell line ac-
counted for 17 to 90% (median 40%) of the analysed metaphases.
332 Meschede et al.

TABLE II. Details of 55 Cases With Prenatally Diagnosed Sex Chromosome Polysomy
Gestational Local or Pregnancy
Diagnostic week at Indication for referreda continued or Special case
Case Karyotype method diagnosis prenatal diagnosis case terminated features
1 47,XXY CVS 15 Maternal age Local Continued Counseling by
telephone
2 47,XXY AC 18 Abn. triple test Referred Continued
3 47,XXY CVS 15 Maternal age Local Continued
4 47,XXY AC 19 Abn. triple test Referred Continued ICSI pregnancy
5 47,XXY AC 21 Maternal age Referred Terminated
6 47,XXY AC 21 Not documented Referred Continued
7 47,XXY AC 21 Maternal age Local Continued
8 47,XXY AC 21 Abn. triple test Local Continued
9 47,XXY CVS 15 Maternal age Local Continued
10 47,XXY AC 20 Abn. triple test Referred Continued
11 47,XXY AC 17 Maternal age Referred Continued
12 47,XXY AC 19 Anxiety Referred Terminated Abnormal
ultrasound
13 47,XXY CVS 15 Maternal age Local Continued
14 47,XXY AC 20 Maternal age Local Continued
15 47,XXY AC 18 Maternal age Local Continued Abnormal
ultrasound
16 47,XXY AC 20 Anxiety Referred Terminated
17 47,XXY AC 17 Maternal age Referred Continued
18 47,XXY CVS 14 Maternal age Local Continued
19 47,XXY AC 22 Maternal age Local Continued
20 47,XXY AC 21 Maternal age Local Continued Twin pregnancy
21 47,XXY CVS 12 Abnormal Local Continued
ultrasound
22 47,XXY AC 19 Maternal age Local Continued
23 47,XXY AC 20 Previous 45,X Local Terminated
24 47,XXY/46,XY AC 20 Maternal age Local Continued
25 47,XXY/46,XY CVS 13 Maternal age Local Continued
26 47,XXY/46,XY CVS 14 Maternal age Local Continued
27 47,XXY/46,XY AC 19 Maternal age Referred Continued
28 47,XXY/46,XY CVS 12 Maternal age Local Continued
29 47,XYY AC 23 Anxiety Referred Continued
30 47,XYY CVS 17 Maternal age Local Continued
31 47,XYY AC 20 Previous NTD Local Continued
32 47,XYY AC 23 Abnormal Local Continued
ultrasound
33 47,XYY AC 20 Anxiety Referred Continued
34 47,XYY AC 20 Maternal age Local Continued
35 47,XYY AC 23 Abnormal Local Continued
ultrasound
36 47,XYY AC 20 Abnormal Local Continued
ultrasound
37 47,XYY AC 22 Maternal age Referred Continued
38 47,XYY AC 19 Anxiety Referred Terminated
39 47,XYY/46,XY CVS 14 Maternal age Local Continued
40 47,XYY/46,XY CVS 15 Maternal age Local Continued
41 47,XXX AC 19 Maternal age Referred Continued
42 47,XXX AC 20 Maternal age Referred Continued
43 47,XXX AC 20 Abnormal Local Terminated Triplet pregnancy
ultrasound
44 47,XXX AC 19 Maternal age Referred Continued
45 47,XXX AC 19 Maternal age Referred Continued
46 47,XXX AC 21 Not documented Referred Continued
47 47,XXX CVS 15 Risk for monogenic Local Continued
disease
48 47,XXX CVS 14 Maternal age Local Continued
49 47,XXX AC 19 Maternal age Referred Continued
50 47,XXX AC 19 Maternal age Referred Terminated
51 47,XXX AC 19 Maternal age Referred Continued
52 47,XXX CVS 12 Abnormal Local Continued
ultrasound
53 47,XXX/46,XX CVS 14 Maternal age Local Continued
54 47,XXX/46,XX AC 19 Maternal age Referred Continued
55 47,XXX/46,XX AC 21 Maternal age Referred Continued
a
Referred cases: cytogenetic diagnosis made elsewhere, patient referred for genetic counseling only.
AC, amniocentesis; CVS, chorionic villus sampling; NTD, neural tube defect; triple test, triple serum marker screening (␣-fetoprotein, human chorionic
gonadotropin, and unconjugated estriol); ICSI, intracytoplasmic sperm injection; Abn, Abnormal.

Four pregnancies with nonmosaic Klinefelter syn-
drome, two with a nonmosaic 47,XXX karyotype, and
one with nonmosaic 47,XYY were terminated. This cor-
responds to termination rates of 17.4, 16.7, and 10.0%
for the nonmosaic XXY, XXX, and XYY cases and 0%
for the mosaics. In one of the aborted Klinefelter syn-
drome pregnancies (case 12), the couple had made the
preliminary decision to keep the child. However, ultra-
sound scanning performed after genetic counseling un-
expectedly revealed skin edema, brachycephaly, tho-
racic hypoplasia, and a positive “lemon sign.” The preg-
nancy was terminated because of the presence of these
abnormalities. Another aborted Klinefelter syndrome
pregnancy (case 23) was the second gestation of a
couple that had previously lost a hydropic fetus with
45,X Ullrich-Turner syndrome. One termination was
the selective fetocide of a 47,XXX fetus in a triplet preg-
nancy (case 43). This fetus had marked skin edema
that was the indication for invasive prenatal diagnosis.
The other two triplets had a normal ultrasound scan
and normal karyotypes and were carried to term. All
other counselees who opted for a termination had nei-
ther abnormal ultrasound findings nor a history of pre-
vious inadvertant reproductive outcomes. Their demo-
graphic and clinical characteristics (age, indication for
prenatal diagnosis, and gestational age at diagnosis)
did not differ significantly from the rest of the study
cohort (Table II). The diagnosis of sex chromosome
polysomy was made between the 19th and 21st gesta-
tional week in all seven cases in which an induced
abortion was performed. The decision to terminate did
not correlate positively with early gestational age. Of
seven women electing a pregnancy termination, five
were referred from outside institutions. The termina-
tion rate in the referred subcohort was 20.8% and in
the subcohort primarily diagnosed at our center 6.5%.
DISCUSSION
Seven of 55 pregnancies (12.7%) with a prenatally
diagnosed sex chromosome polysomy were terminated
after genetic counseling at our institution. This is a low
rate compared with data presented by other groups
[Tannenbaum et al. 1986; Holmes-Siedle et al., 1987;
Verp et al., 1988; Robinson et al., 1989; Abramsky and
Chapple, 1997]. In a collaborative study from Finland
and the United Kingdom induced abortion rates for
Klinefelter, triple X, and XYY syndromes of 66, 33, and
37% were reported [Holmes-Siedle et al., 1987]. Simi-
larly, a study from the United States showed that 45%
of gestations with Klinefelter syndrome were termi-
nated, as were 32 and 35% of gestations with the XYY
and XXX karyotypes [Robinson et al., 1989]. Abramsky
and Chapple [1997] reported recently that “about half”
of the 47,XXY and 47,XYY cases diagnosed prenatally
in the United Kingdom’s North Thames Health region
had a termination of pregnancy.
One of the possible reasons for the low termination
rate in our study cohort are cultural differences in the
perception of particular types of prenatally diagnosable
disorders [Wertz, 1995]. However, a low termination
rate is not a universal finding in our prenatal diagnosis
program. Only 2% of pregnancies with fetal Down syn-
Prenatally Diagnosed Klinefelter Syndrome 333
drome diagnosed at our institution between 1989 and
1996 at a gestational age of less than 25 weeks were
continued, whereas 86% were terminated and 12%
were lost spontaneously in the interval between the
diagnostic procedure and communication of the result
(I. Nippert et al., unpublished observation).
Which factors determine the parental decision about
continuation or termination of a chromosomally or oth-
erwise abnormal pregnancy is generally poorly under-
stood. The parents’ perception of the expected disabil-
ity is likely to play an important role [Nippert and
Horst, 1994]. Also, the specialty of the medical profes-
sional providing the counseling may have an impact; in
the series reported by Holmes-Siedle et al. [1987],
clearly more pregnancies with an SCA were terminated
when postdiagnosis counseling was done by an obste-
trician rather than by a geneticist. Direct contact be-
tween the parents and a counselor with special exper-
tise in sex chromosomal anomalies results in lower ter-
mination rates than when counseling is performed by a
medical caretaker who contacted a specialist for advice
[Robinson et al., 1989]. Our data suggest a similar
trend. The termination rate was higher among couples
who were referred from outside institutions and had
received their initial information about the SCA there.
Although we did not specifically document this, it can
be assumed that most of these primary information
providers did not have a formal training in genetics.
In accordance with the principle of nondirectiveness
[Kessler, 1997], patients counseled at our institution
about an SCA in their unborn child were not given
direct advice to continue the pregnancy or to abort it.
The geneticist considers as the foremost task to give
the counselees a realistic and comprehensive account of
the type of SCA under discussion. It is pivotal to base
this provision of factual information on methodologi-
cally sound follow-up studies. Ideally, counselees
should then be able to reach at an informed and re-
sponsible decision in accordance with their personal
views and reproductive goals [World Health Organiza-
tion et al., 1995]. To what extent such nondirectiveness
can actually be achieved in day-to-day counseling prac-
tice has been questioned both on theoretical and em-
pirical grounds [Clarke, 1991; Wolff and Jung, 1995;
Bartels et al., 1997; Bernhardt, 1997; Michie et al.,
1997]. It is difficult to determine where a supportive
attitude of the counselor blends into directiveness. Al-
though paternalism needs to be avoided and it remains
the counselor’s duty to take a basically neutral position
and respect patient autonomy, there may still be some
space for serving to many patients’ legitimate desire to
receive some professional guidance for a difficult deci-
sion.
With regard to the pivotal issue of mental develop-
ment, we emphasize that frank mental retardation is
not more common among children with a 47,XXY,
47,XYY, or 47,XXX karyotype than in peers, and that a
supportive environment may help to counteract devel-
opmental problems should they occur. On the average,
such children score 10 to 15 points lower on the intel-
ligence scale than peers with a normal set of chromo-
somes [Bender et al., 1993; Rovet al., 1995]. However,
it is important to note that their mean global IQ of
334 Meschede et al.
around 90 falls well within the normal range and is
compatible with a productive and socially well-
adjusted life. In fact, according to population-based
data from the United Kingdom [Abramsky and
Chapple, 1997], many carriers of a 47,XXY or 47,XYY
karyotype appear to remain undiagnosed for a lifetime.
This is a strong indicator that neither their physical,
their behavioral, nor mental status necessarily
prompts a chromosome analysis.
ACKNOWLEDGMENTS
We thank the genetic counselors at the Institute of
Human Genetics, Dr. S. Tercanli at the Women’s Hos-
pital, and Prof. Dr. J. Brämswig at the Children’s Hos-
pital for clinical support.
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