Download Swyer syndrome in a woman with pure 46,XY gonadal dysgenesis

CASE REPORT
Swyer syndrome in a woman with pure 46,XY gonadal dysgenesis
Maharjan Anita1, Min Jie2, Hong Li*
Abstract
Swyer syndrome or pure gonadal dysgenesis is a genetic aberration characterized by a 46,XY karyotype which are
phenotypical females, with female genitalia at birth and normal Müllerian structures. The condition usually becomes
apparent first in adolescence with delayed puberty and primary amenorrhea. This case report describes a 27 years old
woman with primary amenorrhea and undeveloped breast. The patient had pure 46,XY gonadal dysgensis with
hypoplastic uterus, estrogen treatment for amenorrhea, no neoplastic changes on the histopathology report. The
patients with gonadal dysgenesis and 46, XY karyotype should be referred for bilateral gonadectomy because of the
high risk of neoplastic transformation. Early diagnosis and treatment could help these patients have a normal sex life
and carry a fetus in an immature uterus using donor oocytes and hormonal replacement..
Keywords: Swyer Syndrome, 46,XY pure gonadal dysgenesis, primary amenorrhea, dysgerminoma
Address of Authors:
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University,Jiefang Road 238, Wuhan, Hubei,
China.
1. [email protected], 008615072389065;
2. [email protected], 008615827649335
* Corresponding author [email protected], 008613995600099
Introduction
Swyer syndrome or pure gonadal dysgenesis
is a genetic aberration characterized by a 46,
XY karyotype which are phenotypical
females, with female genitalia at birth and
normal Müllerian structures. Patients are
generally diagnosed in adolescence with
delayed pubertal development and most often
with primary amenorrhea due to the fact that
gonads have no hormonal or reproductive
potential. [ 1 ] The psychosocial and
reproductive implications of the condition
require
multidisciplinary
management
involving pubertal induction, psychosocial
support
and
assisted
reproductive
technologies. In addition, streak gonads have
30% risk of development of gonadoblastoma
and 50% to 60% risk of germ cell
malignancies, mainly dysgerminoma. [ 2 ]
Therefore, prophylactic gonadectomy is
recommended once diagnosis is made.
Management of Swyer syndrome is in line
with other causes of ovarian failure and
involves induction of puberty with estrogen
to develop secondary sexual characteristics
and long-term combined replacement therapy
with estrogen and progesterone. [1] It has been
hypothesized that women with Swyer
syndrome have a particularly severe degree
of estrogen deficiency and according to the
definition they are completely devoid of any
gonadal steroid production.
Case report
A 27-year old, single, Chinese female
presented with a history of primary
amenorrhea with pure gonadal dysgenesis
was admitted to the hospital. The patient
initially had primary amenorrhea, few pubic
and axillary hair with undeveloped breast
(Taner Stage II). She was treated with Climen
(Estrogen estradiol valerate and cyproterone
acetate) at the age of 20 after which
menstruation
started.
Menstruation
disappeared when she stopped pills. Later on,
she continued her treatment and had
menstruation till now with the regular cycle
of 5 days intervals of 27-30 days. She had
average height with undeveloped breast,
normal vagina and cervix, no apparent
somatic abnormalities and no clitoral
enlargement or any evidence of virilization.
Sonographic examination was performed
which showed hypoplastic uterus with
unremarkable ovaries. Karyotype studies
were performed to confirm the diagnosis of
pure 46, XY gonadal dysgenesis. Laboratory
studies showed a serum FSH level of
68.05mIU/mL, LH level of 36.9305mIU/mL,
T level of 47.88ng/dL which was within the
normal range for women.
retroverted uterus about 3cm×3cm×2cm
with smooth surface was seen along with
fallopian tubes on left and right side holding
a piece of tissue (looked like streak gonads)
measuring
2cm×2cm×1cm
and
4cm×3cm×2cm respectively. Right side of
gonad was covered by dense connective
tissue of 1cm×2cm×1cm. Tissues were sent
for frozen section which suspected a testis.
Based on the agreement with the patient and
her family, bilateral gonadectomy and
salpingectomy were performed and sent for
the pathological studies. Histopathological
study of the left gonad revealed fibrous tissue
whereas right gonad revealed the nodular
distribution of atypical cells with translucent
cytoplasm with fibrous tissue hyperplasia and
infiltration of lymphocytes, which is
illustrated by Figure 1. Similarly,
histopathological study of the right dense
connective tissue suspected short spindle
cells of ovarian stroma with calcification.
Immuno-histochemical report showed that
the tumor cells for CD117 was positive as
shown in Figure 2. Similarly, CD99 and P53
were also found positive but negative for
PLAP, CK, inhibin, SMA, CD3, CD20 and
CD21.
Figure 1: The nodular distribution of atypical cells with
fibrous tissue hyperplasia and infiltration of lymphocytes
Laparoscopic gonadectomy was scheduled
for the patient. During the operation,
Figure 2: Tumor cells positive for CD117
Discussion
The Swyer syndrome, 46,XY gonadal dysgenesis
is a rare chromosomal defect seen in female
phenotypic rare condition of sexual abnormality.
[3 ]
Patients are normally present with small
or undeveloped breast but normal axillary
and pubic hair. The external genitalia are
phenotypically females, the upper part of the
vagina and tubes are normal or reduced in
size and the uterus is normal but undeveloped.
[4]
Patients suspected to suffer from Swyer
syndrome are first subjected to laboratory
testing for confirmation of the diagnosis.
Early diagnosis is important for several
reasons: firstly, because of the high risk of
neoplastic transformation in the dysgenetic
gonads; secondly, early institution of
estrogen therapy for induction of puberty;
thirdly, to allow adequate hormone replacement therapy to prevent osteoporosis. [5]
Various karyotypes can be observed as 45,X,
46,XX, 46,XY, 45,X/46,XY, 47,XXY or
more complex mosaïcisms. [6] The etiology of
46,XY gonadal dysgenesis is believed to be
deletion of short arm of Y chromosome
involving the sex determining region of Y
(SRY) gene, mutation in other genes leading
to inhibition of SRY function, or mutation of
SRY itself. [3]
In this case, the frozen section of the gonads
suspected a testes and the diagnosis was done
at the age of 27 .In order to avoid the risk of
malignant
transformation,
bilateral
gonadectomy and salpingectomy were
carried out. In 2010, Negar et al. [1]
hypothesized that chromosome Y contains a
gonadoblastoma which is responsible for
benign tumor, which may also develop
bilaterally and coexist with other neoplasms
such as dysgerminoma. Hence, the patients
with gonadal dysgenesis and 46, XY
karyotype should be referred for bilateral
gonadectomy because of the high risk of
neoplastic
transformation.
Therefore,
females with Swyer syndrome required close
follow up because of the high risk of
neoplastic transformation in the dysgenetic
gonads.
In this case, after estrogen therapy patient had
her first menstruation cycle but menstruation
was disappeared when she stopped pills and
the histopathology report also showed fibrous
tissue. As dysgenetic gonads composed of
only fibrous tissue; they do not exhibit
hormonal function and gametogenesis or any
structure that allow them to be identified as
either ovaries or testicle. [4] Hence, an
additional estrogen replacement therapy will
be helpful for the development of secondary
sexual characteristics and menstruation. [7 ]
Presence of XY genotype and H-Y antigen
does not affect the uterine and the
endometrial response. There are a number of
case reports of normal pregnancies and
successful delivery in these patients with the
help of artificial reproductive techniques
(ART). [8,9,10]
Thus, early diagnosis and treatment could
help these patients have a normal sex life and
carry a fetus in an immature uterus using
donor oocytes and hormonal replacement.
And after gonadectomy, long term estrogen
therapy should be prescribed for its effect on
vaginal
epithelial,
osteoporosis
and
cardiovascular system. Therefore, further
studies should be performed to find the exact
factors affecting the uterus size, amenorrhea
and to improve the methods of inducing
puberty in these patients. [1]
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