Turner's syndrome (TS) is a common chromosomal disorder affecting females, characterized by the absence or alteration of the second sex chromosome, leading to various physical and developmental issues. It occurs in approximately 1 in 2500 to 3000 live-born girls and can present with symptoms like short stature, primary amenorrhea, and cardiovascular anomalies. Diagnosis may involve prenatal screening, karyotyping, and clinical assessments, while management strategies include hormone therapy and monitoring for associated conditions.

1. Turner's Syndrome

2. Review Article
INTRODUCTION
Turner’s syndrome (TS) is one of the most common
chromosomal abnormalities, first described by Henry
Turner in 1938 [1]. It is a disorder in females characterized
by the absence of all or part of a normal second sex
chromosome, leading to a constellation of physical
findings. Turner’s syndrome occurs in 1 in 2500 to 1 in
3000 live-born girls [2,3].
GENETICS OF TURNER’S SYNDROME
Approximately half have monosomy X (45,X), and 5 to
10% have a duplication (isochromosome) of the long arm
of one X (46,X,i(Xq)). The X chromosome abnormality
may occur as a random event during the formation of
reproductive cells (monosomy X) or may be inherited
(nondisjunction or mosaicism). Mosaic Turner syndrome
occurs as a random event during cell division in early fetal
development. As a result, some of an affected person’s
cells have the usual two sex chromosomes (either two X
chromosomes or one X chromosome and one Y
chromosome), and other cells have only one copy of the X
chromosome.
Turner’s syndrome is a good example of pheno-geno
correlation (Table 1) [4].
The short stature–homeobox (SHOX) gene, located in
the pseudoautosomal region of Y and Xp is probably not
the only gene responsible for the skeletal features.
Aneuploidy itself may contribute to growth failure. Loss of
the testis-determining factor (SRY) gene locus on the short
arm of the Y chromosome (e.g., 46,X,del(Yp)) also leads
to the phenotype of TS, even without a 45,X cell
population. Infants with a 45,X monosomy are the most
likely to have congenital lymphedema [5]. Cardiac
anomalies are most prevalent in women with pure 45,X
monosomy and tend to be less common in those with an
isochromosome Xq karyotype. Learning disabilities more
common among patients with a 45,X karyotype than
among those with a 45,X/46,XX karyotype. Patients with
a karyotype of 45,X/46,XX or 45,X/47,XXX are the most
likely to have spontaneous menarche and fertility. As a
group, women with mosaicism for 45,X/46,XX are
marginally taller than other women with TS [6].
Turner’s syndrome should be suspected in any
newborn girl with edema or hypoplastic left heart or
coarctation of the aorta, since the frequency of both
conditions is increased among children with TS.
Approximately one third of girls with TS receive the
diagnosis in midchildhood on investigation of short
stature. The diagnosis should be excluded in any teenage
girl with primary or secondary amenorrhea, especially if
she is short. Clinical features of TS are briefly described
in Table 2 [7-9].
DIAGNOSIS
Diagnosis can be done prenatally based on the finding
of fetal edema on ultrasonography; abnormal levels of
human chorionic gonadotropin, unconjugated estriol, and
alpha-fetoprotein on screening of maternal serum (triple
screening); or abnormal results of fetal karyotyping
335 Apollo Medicine, Vol. 6, No. 4, December 2009
TURNER’S SYNDROME
Niti Agrawal, Mukul Gupta and S K Wangnoo
Apollo Centre for Obesity, Diabetes and Endocrinology (ACODE), Indraprastha Apollo Hospitals, Sarita Vihar,
New Delhi 110 076, India.
Correspondence to: Dr Niti Agrawal, Department of Endocrinology, Indraprastha Apollo Hospitals, Sarita Vihar,
New Delhi 110 076, India.
Turner syndrome (gonadal dysgenesis) is one of the most common chromosomal abnormalities occuring 1 in
2500 to 1 in 3000 live-born girls. It is an important cause of short stature in girls and primary amenorrhea in
young women that is usually caused by loss of part or all of an X chromosome. This review briefly summarises
the current knowledge about the syndrome and the management strategies.
Key words: Turner’s syndrome

3. Apollo Medicine, Vol. 6, No. 4, December 2009 336
Review Article
levels are recommended for those patients with
abnormalities of the renal collecting system that
predispose to obstruction.
• Perform echocardiography, MRI examination of the
heart, or both upon diagnosis. Evaluate 4-limb blood
pressures secondary to the high incidence of
coarctation of the aorta. A cardiologist should
monitor abnormalities. Because of the risk of aortic
dissection, cardiovascular examinations should be
repeated every 5 years during adulthood and prior to
assisted reproduction. A complete cardiovascular
evaluation should be completed prior to attempting
assisted reproduction.
• Bone age is usually normal prior to adolescence but
is delayed afterward because of the lack of estrogens.
Obtain bone age before starting growth hormone or
estrogen therapy. Growth hormone does not increase
height if the epiphyses are fused.
• Osteoporosis is common but may be overdiagnosed
in short individuals. Measure bone density initially in
adults and 3 years later.
• Infants diagnosed at birth should have a hearing
assessment in the nursery. Otherwise, formal hearing
assessment is recommended at age 1 year and before
entering school. Formal re-evaluation every 5 years
has been recommended.
• Patients are suspected of having a high risk of keloid
formation. This must be taken into consideration if
cosmetic surgery is contemplated because keloids
may negate any gain from such procedures.
• Subacute bacterial endocarditis (SBE) prophylaxis is
required prior to any dental or surgical procedure in
women with cardiac valve disease to prevent SBE.
performed because of advanced maternal age. Turner’s
syndrome may also be diagnosed in utero through
amniocentesis or chorionic villus sampling. Affected
fetuses often abort spontaneously. Karyotyping of a blood
sample is definitive in most cases.
Levels of lutenizing hormone (LH) and follicle
stimulating hormone (FSH) may be elevated secondary to
ovarian failure. One should assess both LH and FSH levels
prior to initiating estrogen replacement therapy.
Ultrasound of the reproductive organs and kidneys as well
as a pelvic examination may show abnormal development.
Patients with 45,X/46,XY mosaicism may have mixed
gonadal dysgenesis and are at a high risk for
gonadoblastoma. Early prophylactic excision of the
gonads is thus recommended in all Turner mosaics with Y
chromosome material detected on routine karyotyping.
Additional tests and follow up:
• Thyroid function tests for evaluation of immune
mediated thyroid disorders. TSH measurements
should be repeated every 1-2 years or if symptoms
develop because patients may develop
hypothyroidism at a later age.
• Screening for diabetes mellitus is best performed by
obtaining a fasting glucose level or hemoglobinA1c.
• If virilization occurs, a search for Y chromosomal
material by fluorescent in situ hybridization (FISH)
or polymerase chain reaction (PCR) is necessary as
part of an evaluation for possible gonadoblastoma.
• At diagnosis, perform ultrasonography of the
kidneys and renal collecting system. Annual urine
cultures and measurement of BUN and creatinine
Table 1. Genotype-Phenotype correlation
Genotype Phenotype
Loss of interstitial or terminal long-arm material Short stature and primary or secondary ovarian failure
of the X chromosome (Xq)
Very distal Xp deletions Short stature and the typical skeletal changes only
Loss of region at Xp22.3 Neurocognitive problems
Ring or marker chromosome Increased risk of mental retardation and atypical phenotypic
features
Aregion on Xp11.4 Critical for the development of lymphedema
Hearing loss (SNHL and conductive deafness) lack a short arm of an X chromosome
45,X/45,XY mosaicism Increased risk of gonadoblastomas
Isochromosome Xq 46,Xi(Xq) Increased risk for hypothyroidism (Autoimmune thyroid
disease) and inflammatory bowel disease, autoimmunity

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337 Apollo Medicine, Vol. 6, No. 4, December 2009
Table 2. Clinical features
Short stature (95%) Partially due to the loss of one copy of the SHOX gene on the X-chromosome
(important for long bone growth).
Bone abnormalities Disproportionately short legs (abnormal upper-to-lower segment ratio), squarely shaped
chest, widely spaced nipples, cervical vertebral hypoplasia, scoliosis, genu valgum,
increased carrying angle, cubitus valgus, short metacarpals and metatarsals.
Developmental and Most people have normal intelligence. 10%, irrespective of karyotype, have substantial
behavioral problems developmental delays, need special education, and require ongoing assistance in adult life.
70% have learning disabilities affecting nonverbal perceptual motor and visuo-
spatial skills. Typical female-sex identification.
Puberty/Reproduction Most females with TS do not enter puberty spontaneously because of the early gonadal
failure and subsequent estrogen deficiency. Spontaneous breast development is either
minimal or does not occur, and primary amenorrhea is usual. Spontaneous pregnancy
occurs in less than 5% of women, the majority occurring in those with mosaicism. Women
with TS who do become pregnant may be at increased risk from cardiovascular
complications.
Congenital heart disease In around 23 to 40%. Bicuspid aortic valve is the most common. Coarctation of the aorta
affects approximately 10% and is an important cause of hypertension. Other: partial
anomalous venous drainage and mitral valve prolapse.
Lymphedema Mild: webbed neck, ptosis, and a low posterior hairline. Lymphedema of the hands and feet
may be present at birth but often resolves.Severe: results in fetal wastage as a consequence
of severe generalized lymphedema, but spontaneous resolution can occur with subsequent
live birth. Nail dysplasia (pitting nails and lateral hyperconvexity) pathognomonic ofTS is also
thought to be secondary to lymphedema.
Hypertension 7-17% of children and 24-40% of adults. ? secondary to small vessel renovascular disease.
Ethinyl E2 as estrogen replacement therapy may exacerbate hypertension, but the use of
natural estrogens and GH therapy does not seem to influence blood pressure.
Insulin resistance Type 2 diabetes mellitus is 2-4 times more common. Impaired glucose tolerance is even
more prevalent, affecting 10-34%. Obesity may be related, in part, to estrogen deficiency.
Kidney malformations Affects ~ 1/3 of individuals with TS. Double collecting system or absent kidney, pelvic or a
horseshoe kidney. Risk of pyelonephritis and pelvoureteric obstruction is increased, thus
increasing the risk of chronic renal impairment. Renovascular abnormalities are also more
prevalent in TS.
Osteoporosis There is a reduction in peak bone mass by 25% in women with TS.
Hypothyroidism 25-30% patients with TS. Up to 50% have positive thyroid autoantibodies. The incidence of
Graves’disease is not increased in TS.
GI disorders Feeding problems, gastroesophageal reflux, and failure to thrive occur in infants (anatomical
differences in the oropharynx as well as oral motor immaturity). TS is associated with a
greatly increased risk of developing ulcerative colitis and Crohn’s disease. There may be an
increased incidence of celiac disease among patients with Turner’s syndrome.
Gonadoblastoma Risk increases with age and is estimated to be 2% at age 10 yr and 27.5% at age 30 yr.
Malignant transformation occurs in 60% of these tumors, with 50% developing into
dysgerminomas and 10% into other malignant germ cell tumors. Larger tumors are more
likely to harbor a malignancy. They may produce androgens or estrogens, resulting in
virilization or feminization, respectively.
Otological disorders Majority of infants and children with TS have recurrent otitis media, which is probably due to a
combination of small, dysfunctional eustachian tubes and palatal dysfunction.The frequency
of ear infections decreases with age and growth of facial structures. Progressive
sensorineural hearing loss is a major feature of TS in adults.
Ophthalmic disorders Strabismus occurs in about 18% and ptosis in 13%. Cataracts and nystagmus also occur
more commonly in patients withTurner’s syndrome. Red–green colorblindness is found with
the same frequency as in normal males.
Skin disorders Multiple pigmented naevi are very common (27%). Immune-related dermatological
conditions such as psoriasis, alopecia, and vitiligo also occur with slightly increased
frequency. The prevalence of psoriasis in females with TS is twice that of the general
population.Additionally, alopecia areata is 3 times more common in women with TS.

5. Apollo Medicine, Vol. 6, No. 4, December 2009 338
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GROWTH HORMONE (GH) THERAPY IN TS [10]
Heights of girls with TS should be plotted on TS-
specific growth curves. Provocative GH testing should be
performed only in girls with TS whose growth is clearly
abnormal relative to that expected for TS. No clinical
rationale exists for testing girls with TS whose growth is
consistent with the expected pattern. The advantages and
disadvantages of GH therapy, anabolic steroid treatment,
and orthopedic procedures for increasing height should be
discussed with the patient’s family.
Growth Hormone, with or without anabolic steroids, is
known to accelerate growth in girls with TS. Recent
studies have indicated that, with early diagnosis and
initiation of GH treatment, final height is increased and
can be normalized in most patients with TS. These studies
have also provided evidence that dosages higher than that
currently recommended for TS (0.05 mg/kg per day)
produce a greater increase in final height and no apparent
increase in adverse events. Individualized dosing of GH
should be considered, with the dose adapted in accordance
with the patient’s growth response.
Initiation of GH therapy should be considered as soon
as a patient with TS is below the 5th percentile of the
normal growth curve for girls. For girls younger than 9 to
12 years of age, therapy can be started with GH alone. The
recommended starting dosage is 0.05 mg/kg per day (0.15
IU/kg per day). Growth should be monitored every 3 to 6
months. In girls older than 9 to 12 years of age, or in girls
older than 8 years of age in whom therapy was instituted
when the patient already was far below the 5th percentile
of the normal growth curve, the addition of anabolic
steroid treatment to GH therapy should be considered.
Anabolic steroids (including oxandrolone) should not be
used alone for the promotion of growth. The use of
anabolic steroids in excess results in virilization and
overly rapid skeletal maturation and should be avoided.
Oxandrolone seems to be particularly suited for the
promotion of growth because, uniquely among the
anabolic steroids, it is not aromatized into substances with
estrogenic properties. Oxandrolone should not be used at
dosages above 0.05 mg/kg per day and should not be
administered to girls with TS younger than 8 years of age.
Girls given oxandrolone should be monitored for side
effects.
Therapy may be continued until a satisfactory height
has been attained or until the bone age is more than 14
years and the patient’s height has increased by less than
2.5 cm in comparison with that of the previous year.
When used to induce puberty, estrogen therapy causes
fusion of the epiphyses, a limiting factor in longitudinal
bone growth. Current data indicate that estrogen has no
role as a growth-promoting agent. The initiation of
estrogen therapy should be timed so as to minimize any
negative effect on growth and adult height while inducing
puberty at an approximately normal age.
HORMONE THERAPY IN TS [4]
The presence of normal gonadotropin levels in the first
three to six months of life suggests that residual ovarian
function exists but does not ensure that the initiation and
progression of puberty will be normal. Gonadotropins are
suppressed in childhood, even in those with gonadal
dysgenesis. In many girls with Turner’s syndrome, pubic
and axillary hair will develop spontaneously, but changes
of adrenarche are not indicative of ovarian function. Some
girls have enough residual ovarian function for breast
budding or vaginal spotting to occur, but secondary
amenorrhea will develop. A minority will maintain
ovulatory cycles for a time. Two fifths of girls with 45,X/
46,XX mosaicism will have spontaneous menarche;
however, ovarian failure usually ensues.
If the status of ovarian function in adolescence is
unclear, measurement of follicle-stimulating hormone,
luteinizing hormone, and estradiol levels can help
determine the need for hormone-replacement therapy.
Hormone-replacement therapy should be initiated at about
the age of 14 years. Earlier treatment may result in a
decrement in final height. Psychosocial issues and the
patient’s maturity and wishes also need to be considered.
Girls who have received recombinant human growth
hormone and who have completed most of their growth, as
judged on the basis of bone age or growth velocity, may
start hormone-replacement therapy at the age of 12 years if
they wish. After the first year, the use of a cycling regimen
with a progestational agent is mandatory to minimize the
risk of endometrial hyperplasia and uterine
adenocarcinoma. The effects of hormone-replacement-
therapy on liver function, on bone density, and on the risk
of hypertension, cancer, and obesity in patients with
Turner’s syndrome are uncertain. There has not been an
increased occurrence of breast cancer among patients with
Turner’s syndrome.
Spontaneous fertility is rare among patients with
Turner’s syndrome and is most likely in women with
mosaicism for a normal 46,XX cell lineage, a 47,XXX cell
lineage, or very distal Xp deletions. These women have an
increased risk of spontaneous pregnancy loss, twins, and
aneuploidy in fetuses that are carried to term. Efforts to
cryopreserve ovarian tissue are fairly new, and the
applicability of such techniques to preserve fertility in
women with Turner’s syndrome may be compromised by a
high rate of aneuploid gametes.

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339 Apollo Medicine, Vol. 6, No. 4, December 2009
Physicians should discuss infertility issues and
reproductive options with their patients and reassure them
about their sexual function. It is important to
acknowledge the sense of loss associated with infertility,
on the part of both the patient and her parents. Pregnancy,
by means of gamete intrafallopian transfer with donor
eggs, has been attempted in women with Turner’s
syndrome, with a success rate equal to that in other
infertile women.
LIFE EXPECTANCY
Patients with TS appear to have a decreased life
expectancy, primarily as a result of complications of heart
disease and diabetes.
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