Mosaicism in Turner Syndrome - GGH Journal

icism for 45,X have to exist
before a significant pregnancy
risk is posed? Patients with
Turner syndrome who have
spontaneous menses often
have premature ovarian failure
or menopause. Is our patient at
risk for this? There are no data
to address these questions and
it is clinically unwarranted to
exhaustively search for minor
mosaicism for 45,X in a girl with
short stature or in a woman with
gonadal dysgenesis and no other
features of the Turner syndrome.
Screening follicle-stimulating
hormone (FSH) and
luteinizing hormone (LH) levels
is more likely to accurately
measure ovarian function than
the presence of minor
mosaicism for 45,X and should
be performed when appropriate.
How can one interpret mosaicism
in older individuals?
In males and females alike,
there is an increasing incidence
of monosomy X in tissue culture
with aging.11 No studies have
addressed the tolerable upper
limits of mosaicism for 45,X in
younger individuals. In the
absence of clinical features, the
diagnosis of Turner syndrome
should not be made on the
basis of minor mosaicism for
45,X cell line in women over the
age of 30. As Horsman et al13
suggested, the implications of
mosaicism for childbearing are
unclear and the results of karyotyping
do not allow for discriminate
predictions or management
of patients.
How does mosaicism for a
V or V-derived chromosome
impact the management and
treatment of the patient with
Turner syndrome?
Mosaicism for 45,X/46,XV or
45,X/46,X, abnormal V chromosome
constitution is a special
situation in Turner syndrome.
These patients may be phenotypically
classic for Turner syndrome
or may be ascertained
because of ambiguous genitalia
or minor genital anomalies
such as hypospadias and
undescended testes. The presence
drome.19-22 We believe some
of a Y chromosome con-
mild spontaneous breast develdrome.19-22
fers an increased risk for opment is not unusual in Turner
gonadoblastoma (15% to 30%) syndrome and should not
in the gonadal streaks.14-17 This prompt gonadectomy in a nonrisk
increases with age. All V-bearing individual. Gonadoblastoma
patients with Turner syndrome
also has been report-
and a Y chromosome should ed in patients who are mosaic
undergo prophylactic gonadectomyments.
for rings, markers, and frag-
It is often difficult to
It has been suggested that determine the chromosomal origin
those individuals with a nonfluorescent
of a marker chromosome in
Y and/or those without patients with Turner syndrome.
certain repetitive Y -specific The assumption has been
DNA sequences may not be at made that it is only those markers
risk for gonadoblastoma, In at
derived from a Y chromo-
least 1 of our patients this was some that confer an increased
not true. Thus, until further studies
risk for gonadal malignancy.
are done or better methods of Until such time when molecular
determining the presence of Y techniques for detecting those
loci that confers the risk for Y -specific sequences that confer
malignancy are available, prophylactic
the risk for gonadoblas-
gonadectomy in any toma23 can be employed routinely
patient with even a segment of
and inexpensively in
a Y chromosome remains the patients with Turner syndrome,
appropriate treatment.
management of patients who
There have been a few are mosaic for rings and fragments
reports of gonadoblastoma in
should be individualized.
individuals with 45,X Turner Routine screening with ultrasound
syndrome in whom there was
imaging, prophylactic
no evidence of mosaicism for gonadectomy, or judicious nonintervention
the Y chromosome.18 Interestingly,
may all be appro-
at least 2 of the reported priate.
patients had spontaneous What is the significance of
menses and ovulated for a prenatally detected mosaicism
number of years prior to
to the patient and the
gonadal failure. Katayama et clinician?
al18 suggested that spontaneous
Perhaps the most difficult
breast development problem posed by mosaicism
might be a marker for those for Turner syndrome is its prenatal
patients who were at risk for
detection. Mosaicism and
gonadoblastoma, but who did pseudo mosaicism in amniotic
not have a Y chromosome or fluid cell cultures are common
segment, because such and may be found in 3.5% of
occurred in his patients with samples.24 When mosaicism for
gonadoblastoma and in some 45,X/46,XX or 45,X/46,XY is
of those reported in the litera-ture. found at prenatal diagnosis, it
This may not be a reliable presents significant problems in
marker, as we have seen spontaneous
interpretation. The mosaicism
breast development may result from an in vitro arti-
(Tanner 2 and 3) in at least fact, may represent mosaicism
10% of our adult patients with limited to the placenta, or may
45,X/46,X,i(Xq) and other "nonrisk-bearing"
be indicative of true fetal
karotypes, none mosaicism. In a survey25 of 92
of whom have developed cases of 45,X/46,XY mosaicism
gonadoblastoma. In addi-tion, diagnosed prenatally, 76 were
no breast development available for clinical examination
occurred in 5 of 8 cases of
either after termination or at
gonadoblastoma in non- Y -bearing
delivery. Of these, 75 were
women with Turner syn-
phenotypic males and 1 was
a