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Case Report
Mosaic Turner Syndrome Presenting with a 46,XY Karyotype
Melody Rasouli,1Katherine McDaniel,2Michael Awadalla ,2and Karine Chung2
1University of Southern California Keck School of Medicine, Los Angeles, CA, USA
2Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
Correspondence should be addressed to Michael Awadalla; michael.awadalla@med.usc.edu
Received 16 December 2018; Revised 17 March 2019; Accepted 18 March 2019; Published 11 April 2019
Academic Editor: Seung-Yup Ku
Copyright © Melody Rasouli et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Although Turner syndrome is most commonly associated with a ,X genotype, other mosaic genotypes are present in
approximately half of all cases. We describe a case of Turner syndrome with a ,XY genotype by conventional -cell karyotype who
was subsequently found to have a mosaic genotype of % ,X and % ,XY by -cell FISH analysis. Individuals with a mosaic
,X/,XY genotype have a variety of phenotypic presentations ranging from male to female which are not correlated with the
percentage of mosaicism. Our case represents an extreme example where the genotype is predominately ,XY and the phenotype
typical of Turner syndrome.
1. Introduction
Turner syndrome is diagnosed in females based on clinical
presentation combined with a genotype consisting of one
normal X chromosome and complete or partial absence
of the other X chromosome []. Patients with ,X/,XY
mosaicism present with a variety of phenotypes ranging from
most commonly mixed gonadal dysgenesis to others such
as phenotypic males, genital ambiguity, Turner syndrome,
and women with normal female secondary sex characteristics
[, ]. Turner syndrome presents with bilateral streak gonads,
whereas mixed gonadal dysgenesis describes those presenting
with an absent or abdominal streak gonad on one side and
a normal or dysgenic testis on the other. e phenotype in a
,X/,XY mosaic patient likely depends on the distribution
of mosaicism percentage in dierent tissues which has been
shown to dier between blood and gonadal tissue []. is
case is an example where the dominant mosaic genotype in
the blood (,XY) is discordant with the Turner syndrome
phenotype.
2. Case Presentation
A -year-old gravida para Russian female presented
with irregular menses every - months and a -year history
of infertility. Prior to presenting to our institution, she was
seen by a fertility specialist in Russia where a karyotype
analysis was performed. A copy of the result was not available
for review by our clinicians, but the patient believed that
shewasfoundtohavea,XYkaryotype.epatientwas
unaware of any other relevant lab results. e patient under-
went menarche at the age of and had irregular menses
every - months since then. She had an early rst trimester
spontaneous abortion which was detected with a positive
home urine pregnancy test without clinical ultrasound or
pathological conrmation. She had a history of a laparoscopic
appendectomy with a concurrent right salpingectomy. She
did not have any other signicant medical or family history.
Specically she had no family history of irregular menses,
infertility, or premature ovarian failure.
On exam, she was cm tall and weighed kg with a
BMI of . Her vital signs were normal and she had normal
female secondary sex characteristics with Tanner stage V
breast development, Tanner stage V pubic hair growth, a
normal vagina and cervix, and no hirsutism or clitoromegaly.
She was without short stature, scoliosis, high palate, hearing
loss, short or webbed neck, shield chest, cubitus valgus,
shortened fourth metacarpals or metatarsals, genu valgum or
varum, or Madelung deformity of the forearm and wrist.
Laboratory studies showed premature ovarian insuf-
ciency with a follicle stimulating hormone level of
. mIU/mL, a luteinizing hormone level of . mIU/mL,
Hindawi
Case Reports in Obstetrics and Gynecology
Volume 2019, Article ID 3719178, 3 pages
https://doi.org/10.1155/2019/3719178
Case Reports in Obstetrics and Gynecology
F : Pathology of the right and le ovaries shows hypoplastic
ovarian tissue with brotic stroma and an absence of follicles.
an estradiol level of < pg/mL, and a total testosterone level
of < ng/dL. Liver function and thyroid function tests were
within normal limits. A peripheral blood karyotype analysis
of cells at a - band resolution showed a normal
,XY male karyotype (Chromosome Analysis Blood, Quest
Diagnostics). Although this karyotype is consistent with
complete gonadal dysgenesis (Swyer syndrome), the patient’s
clinical history of breast development and menses did not
t this diagnosis. A FISH analysis was performed on
cells for evaluation of SRY and the X centromere to evaluate
for possible Swyer syndrome or low-level mosaicism.
is showed cells with ,XY and cells with ,X
(FISH SRY/X Centromere, Quest Diagnostics) which was
clinically correlated to a diagnosis of mosaic Turner syn-
drome.
Sonographic examination revealed a small uterus mea-
suring . ×. ×. cm, a right ovary measuring . ×
. ×. cm with two simple cysts measuring mm and
mm, a le ovary measuring . ×. ×. cm, and a mm
endometrial echo complex. A CT scan of the abdomen
and pelvis showed normal kidneys. An echocardiogram was
performed and showed no cardiac anatomical abnormalities.
A dual-energy X-ray absorptiometry (DEXA) scan showed
lumbar osteoporosis with a T-score of -..
Due to the increased risk of gonadoblastoma, the patient
was oered and accepted laparoscopic bilateral gonadectomy
and le salpingectomy (her right fallopian tube was surgically
absent) with pelvic washings. On pathologic review, the bilat-
eral gonads were found to possess hypoplastic ovarian tissue
(Figure ) with two small right ovarian serous cysts (Figure )
and no evidence of malignancy. For her osteoporosis, she
was prescribed calcium and vitamin D supplementation and
she preferred to be on cyclic combined oral contraceptives
rather than standard hormone replacement therapy. She was
counseled that pregnancy is an option for her through in
vitro fertilization with donor eggs and she intends to pursue
this when ready for family building. She was counseled that
bisphosphonates are not recommended in women consider-
ing future pregnancy and referred to medical endocrinology
for treatment of osteoporosis with other non-bisphosphonate
medications.
F : Pathology of the right ovary shows benign serous cysts.
3. Discussion
Turner syndrome is associated with multiple chromo-
some abnormalities including ,X and ,X/,XX and
,X/,XXX and ,X/,XY. e ,X/,XY genotype
accounts for approximately -% of cases of Turner syn-
drome []. In a report of prenatally diagnosed cases
of ,X/,XY mosaicism, had male appearing external
genitalia and only one had female genitalia []. In a series
of postnatally diagnosed cases of ,X/,XY mosaicism,
were male ( with mixed gonadal dysgenesis) and had
Turn e r s yn d ro m e [] . Tu r ne r s y n d ro m e with , X/ ,XY
low-level mosaicism may not be detected on standard kary-
otype and FISH analysis of larger numbers of cells can be
useful for diagnosis.
e American College of Medical Genetics (ACMG)
provides guidelines for karyotyping procedure specic to
Turner syndrome. e College recommends karyotyping a
minimum of cells due to the high incidence of mosaicism,
unless mosaicism is encountered within the rst cells.
When there is a high clinical suspicion of Turner syndrome
in a patient with a ,XX karyotype, cytogenetic study of a
second tissue type (such as skin biopsy for cell culture or
buccal smear for FISH) is advised. Additionally, given the risk
of gonadoblastoma with occult Y chromosome mosaicism,
the ACMG recommends cell FISH analysis to probe for
the X and Y centromeres when -cell karyotype results in a
nonmosaic ,X karyotype [].
Women with Turner syndrome who possess Y chromo-
some material have an increased risk of germ cell tumors such
as gonadoblastoma and dysgerminoma. A national cohort
study that included of these patients estimated that, by
age , the cumulative risk of gonadoblastoma is .% (%
CI .-.) []. Although rates of gonadoblastoma in Turner
syndrome patients with Y chromosome material vary by
study from as low as % to as high as %, current evidence
suggests that the rate is approximately %. Prophylactic
gonadectomy is recommended at the time of diagnosis for
patients with Turner syndrome and Y chromosome material
such as ,X/,XY mosaicism [].
Turner syndrome patients with any genotype should
undergo standard testing and treatment for cardiovascular,
Case Reports in Obstetrics and Gynecology
renal, metabolic, endocrine, vision, hearing, and bone min-
eral density abnormalities []. If premature ovarian failure
is diagnosed, hormone replacement therapy is indicated
until the typical age of menopause to induce puberty and
secondary sexual characteristics, stimulate uterine growth,
and prevent bone loss. It is generally recommended to begin
treatment with low-dose E2(-𝜇g/day of transdermal E2or
.mg oral E2per day) at age or and incrementally
increasethedosetoadultdoses(-𝜇g/day of transdermal
E2or -mg oral E2per day) over to years. Transdermal
estradiol is preferred, followed by oral or intramuscular
estradiol. Oral ethinyl estradiol is not recommended, unless
other options are unavailable or for issues relating to patient
preference or compliance as was the case for the patient pre-
sented here. A progestin is added once breakthrough bleeding
occurs or years aer E2is begun to decrease the risk
of endometrial hyperplasia. Progestin can be administered
orally in a cyclic pattern with E2, orally continuously with E2,
or in the form of a progestin containing intrauterine device
[].
Future fertility is an important consideration for patients
with Turner syndrome. Accurate and early diagnosis of
,X/,XY mosaicism can allow for counseling about repro-
ductive potential and pursuing pregnancy with in vitro fer-
tilization with donor egg and/or gestational surrogacy. Suc-
cessful pregnancy outcomes have occurred in patients with
,X/,XY mosaicism as well as ,XY gonadal dysgenesis
following oocyte donation and in vitro fertilization, although
most of the reported cases were delivered by cesarean section
[–]. Although this patient’s uterus measured only . ×
. ×. cm on ultrasound, there is no contraindication to
pregnancy due to uterine size. Uterine size is likely a result of
low estrogen status rather than an indication that the uterus
is unt to carry a pregnancy to term.
In summary, this case demonstrates that Turner syn-
drome with low level mosaicism may be missed by con-
ventional karyotype. Some females diagnosed with Swyer
syndrome may actually have Turner syndrome with low level
mosaicism. Approximately -% of patients diagnosed
with Swyer syndrome do not have SRY mutations [, ],
and Turner syndrome with low level mosaicism may be the
actual cause of gonadal dysgenesis in some of these patients.
In cases where conventional karyotype results do not closely
match the clinical presentation, FISH analysis for low level
mosaicism may be informative.
Conflicts of Interest
e authors declare that they have no conicts of interest.
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