Turner Syndrome


Turner syndrome (TS), also known as congenital ovarian hypoplasia syndrome, occurs when the X chromosome is partially or completely missing in females. Its main clinical manifestations include growth disorders, reproductive system abnormalities, cardiovascular abnormalities, and autoimmune diseases. TS is highly prevalent in China. Timely diagnosis is crucial, and non-invasive prenatal DNA testing can identify TS and other diseases. Treatment of TS mainly involves administration of growth hormone combined with very low doses of estrogen to increase the patients height.

Associated Anatomy

Humans have 46 chromosomes. Chromosomes contain all of your genes and DNA, the building blocks of the body. Two of these chromosomes, the sex chromosomes, determine if you become a boy or a girl. Females normally have two of the same sex chromosomes, written as XX. Males have an X and a Y chromosome (written as XY).

In Turner syndrome, cells are missing all or part of an X chromosome. The condition only occurs in females. Most commonly, the female patient has only one X chromosome. Others may have two X chromosomes, but one of them is incomplete. Sometimes, a female has some cells with two X chromosomes, but other cells have only one.


Turner syndrome results from the following mechanisms.


During meiosis in either parent, a nondisjunction event can occur that leaves the gamete, either oocyte or spermatocyte, with neither X nor Y chromosome. When this gamete combines with a gamete from the other parent (with a normal X chromosome), the embryo lacks the normal two chromosomes. Normally, humans have 46 chromosomes, so this leaves the embryo with 45 chromosomes and a single X chromosome, denoted 45,X (or, sometimes 45,XO, where the “O” is used as a placeholder). This is found in 50% of individuals with Turner syndrome.

Chromosomal structure

An X chromosome can form a ring chromosome for example by losing a portion of the smaller arm, enabling the end of the long arm to wrap around. This is detrimental for the X chromosome in two ways. Either the lost portion itself makes the chromosome less functional, or it causes nondisjunction, as described above. Thus, the causes listed here are partly overlapping.

When such a ring chromosome combines with another ring chromosome in fertilization, the pair is denoted as 46, XrXp-, where rXp- means a ring chromosome missing the small (p) arm of the chromosome.

Another variant of abnormal chromosomal structure is chromosomes with two long arms of the X chromosomes attached, and are called isochromosomes.

Variants of chromosomal structure occur in 30% of individuals with Turner syndrome.

Nonfunctional Y

Very rarely, the embryo has a normal X chromosome and a portion of the Y chromosome. In these cases, the Y chromosome does not have a functional SRY (and so develops as a female), the diagnosis is XY gonadal dysgenesis. It is possible that some Turner syndrome diagnosis is due to gonadal dysgenesis, particularly when it is caused by a large deletion of the Y chromosome.


Each of the causes mentioned above can occur as a mosaicism, that is, some of the cells carry the mutation and some don’t. This happens if the error takes place in one cell after the very first divisions of the early embryo after fertilization. The exact mixture of the two different cell types depends on when the nondisjunction occurred. However, if the nondisjunction occurs after enough divisions, the fraction of abnormal cells is probably not large enough to show any significant effects. For instance, such a 45,X/46,XY individual will develop as a male, without Turner syndrome. Mosaicism is found in about 20% of individuals with Turner syndrome.

No single Y

There is no equivalent syndrome which results in a Y chromosome with no X, as such a condition is fatal in utero. Because an embryo with Turner syndrome doesn’t have a Y chromosome (or, doesn’t have a functional SRY on the Y chromosome), it will move along the path to female development.

Differential Diagnosis

Turner’s syndrome must be differentiated from other diseases that cause latency in secondary sexual characteristics development, such as constitutional delay of puberty, hypopituitarism, delayed puberty, and chromosomal abnormalities including Noonan’s syndrome.


Somatotropin (Nutropin, Genotropin, Humatrope, Norditropin, Omnitrope, Zomacton, Tev-Tropin)

Taller adult heights are associated with earlier treatment and with the duration of treatment prior to induced or spontaneous puberty. With treatment, approximately 50% of patients reach an adult height of 150 cm (59″) or more, compared with an untreated mean adult height of 142 cm (56″).

Oxandrolone (Oxandrin, Anavar)

Of limited use. Some endocrinologists recommend use in patients diagnosed in their teens to achieve a maximum adult height quickly. When used, often combined with growth hormone to allow a lower dose, thus decreasing the potential for adverse effects.

Levothyroxine (Synthroid, Levoxyl, Levothroid, L-thyroxine)

Hypothyroidism is common with Turner syndrome and is treated like any other hypothyroidism. Thyroid hormones influence growth and maturation of tissues. Involved in normal growth, metabolism, and development.


Available in many forms (eg, estradiol [Estrace], conjugated estrogens [Premarin]). Transdermal therapy is more physiologic than oral medications. Restore estrogen levels to concentrations that induce negative feedback at gonadotrophic regulatory centers, which, in turn, reduces release of gonadotropins from pituitary. Increases synthesis of DNA, RNA, and many proteins in target tissues.

Propranolol (Inderal)

Has membrane-stabilizing activity and decreases automaticity of contractions.

Ergocalciferol (Calciferol, Drisdol)

Vitamin D is a micronutrient essential for normal absorption of calcium and phosphorus. Also produced in response to exposure to ultraviolet B light.


The frequency of Turner syndrome is approximately 1 in 2000 live-born female infants. As many as 15% of spontaneous abortions have a 45,X karyotype. Interestingly, 99% of conceptions with 45,X karyotypes spontaneously abort.


Turner syndrome is caused by the absence of one set of genes from the short arm of one X chromosome. In patients with 45,X karyotype, about two thirds are missing the paternal X chromosome. In addition to monosomy X, a similar clinical picture is found with a 46,XXiq karyotype and in some individuals with mosaic karyotypes. A deletion of the SHOX gene can cause a similar skeletal phenotype known as Leri-Weill dyschondrosteosis.

Possible Complications

Mortality associated with Turner syndrome may be increased in the neonatal period because of hypoplastic left heart and coarctation of the aorta and in adulthood because of cardiovascular disease, particularly aortic dissection.Obesity, with associated diabetes mellitus and hypertension, can also contribute to early mortality. Limited epidemiologic studies suggest that life expectancy is reduced by about 10 years. Osteoporosis is common.

Although congenital cardiovascular malformations and aortic dilatation are common among patients with Turner syndrome, they are often undiagnosed until later in life, pointing to the need for a more systematic approach to cardiovascular monitoring.

Renal anomalies found in some individuals may cause a predisposition to urinary tract infections or hypertension. Even in the absence of cardiac or renal anomalies, patients are prone to develop hypertension. Individuals with mitral valve disease or aortic valve disease require subacute bacterial endocarditis (SBE) prophylaxis.

Possible Treatment

Turner syndrome is a lifelong condition. Most people live long and healthy lives, yet some are susceptible to numerous chronic conditions. Health supervision involves careful medical follow-up care, which includes screening for commonly associated chronic diseases. Early preventive care and treatment are also essential.

In childhood, growth hormone therapy is standard to prevent short stature as an adult. The results of a double-blind, placebo-controlled trial show that the combination of growth hormone and ultra-low-dose estrogen in childhood may improve growth in patients with Turner syndrome. The ideal age for initiating treatment has not been established. Taller adult heights occur with the longest treatment durations before the start of puberty.

Estrogen replacement therapy is usually required, but starting too early or using doses that are too high can compromise adult height. Estrogen is usually started at age 12-15 years. Treatment can be started with continuous low-dose estrogens at 12 years, or as early as 5 years. These can be cycled in a 3-weeks on, 1-week off regimen after 6-18 months; progestin can be added later. Some authors believe that conjugated estrogens are contraindicated in pediatric patients. Transdermal estrogens are associated with physiologic estrogen level, and may be preferred treatment, if tolerated.

Growth hormone may have long-term favorable effects on lipids, even after it is discontinued.

Androgen replacement therapy is not the standard of care , but may have favorable effects.

Surgical Care

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 may be required prior to any dental or surgical procedure in women with cardiac valve disease to prevent SBE.


Overall prognosis for patients with Turner syndrome is good.

Even with growth hormone therapy, most individuals are shorter than average. Turner syndrome is not a cause of mental retardation.  They are more likely to be employed than other adult women.

Life expectancy is slightly shorter than average but may be improved by attention to associated chronic illnesses, such as obesity and hypertension.

Almost all individuals are infertile, but pregnancy with donor embryos is possible

Primary Prevention

There is no known way to prevent Turner syndrome.

Although the recurrence risk is not increased, genetic counseling is often recommended for families who have had a pregnancy or child with Turner syndrome.

Risk factors

Risk factors for Turner syndrome are not well known. Nondisjunctions increase with maternal age, such as for Down syndrome, but that effect is not clear for Turner syndrome. It is also unknown if there is a genetic predisposition present that causes the abnormality, though most researchers and doctors treating Turners women agree that this is highly unlikely.

There is currently no known cause for Turner syndrome, though there are several theories surrounding the subject.

Signs or Symptoms

At birth, girls with Turner syndrome may have swollen hands and feet because of lymphedema. In infants, the combination of dysplastic or hypoplastic nails and lymphedema gives a characteristic sausage-like appearance to the fingers and toes. Infants also have a higher incidence of congenital hip dislocation.

During childhood, girls with Turner syndrome usually present with short stature. In older adolescents and adults, presenting symptoms usually involve issues of puberty and fertility as well as short stature.

Short stature

Growth rate in childhood is slightly slower; before age 11 years, some girls have height and growth rates that are well within the normal range, but heights are typically below the 50th percentile. 

  • The adolescent growth spurt is essentially absent.
  • Puberty
  • Adrenarche, the beginning of pubic hair growth, occurs at a normal age.
  • Breast development is absent when ovarian failure occurs before puberty.
  • Primary or secondary amenorrhea occurs with ovarian failure.

Other characteristic physical findings

These may include the following:

  • Dental: A high arched palate, sometimes with dental crowding or malocclusion
  • Nails: Hypoplastic or hyperconvex nails
  • Nevi: Excessive numbers of nevi, when compared to other family members
  • Webbed neck: A broad neck and a low or indistinct hairline
  • Cubitus valgus (increased carrying angle)
  • Madelung deformities of the wrist
  • Short fourth and fifth metacarpals and metatarsals
  • Shield chest: The chest appears to be broad with widely spaced nipples
  • Lymphedema
  • Eyes: Ptosis, strabismus, amblyopia, and cataracts; epicanthal folds can be present; red-green color blindness
  • Ears: Serous otitis media is more common ; the auricles may be posteriorly rotated or low set; hearing loss due to otosclerosis is common in adults
  • GI bleeding: This is usually due to intestinal vascular malformations, but the incidence of Crohn disease and ulcerative colitis is also increased
  • Scoliosis: This occurs in 10% of adolescents with Turner syndrome and may contribute to short stature
  • Hypertension: May be caused by coarctation of the aorta or renal anomalies but often occur even in the absence of such findings
  • Cardiac murmurs: Cardiovascular malformations include hypoplastic left heart , coarctation of the aorta, bicuspid aortic valve, and aortic dissection in adulthood
  • Thyroid: Hypothyroidism develops in 10-30% of patients and is often associated with thyroid enlargement
  • Cutis laxa: Loose folds of skin, particularly in the neck, are signs in newborns; this is a result of resolving lymphedema and occasionally is observed after infancy


Active Not Recruiting

Number of studies: 7



Number of studies: 81


Enrolling by Invitation

Number of studies: 3


Not Yet Recruiting

Number of studies: 7



Number of studies: 29


Results Available

Number of studies: 13


Results Not available

Number of studies: 153



Number of studies: 1



Number of studies: 12



Number of studies: 3


Typical Test

A standard 30-cell karyotype analysis is required for diagnosis of Turner syndrome, in order to exclude mosaicism. Diagnosis is confirmed by the presence of a 45,X cell line or a cell line with deletion of the short arm of the X chromosome (Xp deletion).

The buccal smear for Barr bodies is obsolete. A male phenotype excludes the diagnosis, regardless of karyotype. 

Y chromosome

Patients with Turner syndrome should be investigated for the presence of Y chromosomal material using a Y-centromeric probe. These patients may have malignant gonadoblastomas or testicular tissue. The presence of virilization requires a thorough search for gonadal, adrenal, or midline tumors.

Patients with 45,X/46,XY mosaicism may have mixed gonadal dysgenesis and are at a high risk for gonadoblastoma. These patients may require a prophylactic gonadectomy to prevent death from malignancy.

Patients with ring chromosomes or fragments of chromosomes should be examined for Y chromosomal material for the same reason.


Both LH and FSH may be elevated in untreated patients younger than 4 years. Gonadotropins are later suppressed to normal or near-normal levels, only to rise to menopausal levels after age 10 years. 

Assess both LH and FSH levels prior to initiating estrogen replacement therapy.

Thyroid function tests

Because of the high prevalence of hypothyroidism in Turner syndrome, obtain thyroid function tests at diagnosis.

Thyroid-stimulating hormone (TSH) measurements should be repeated every 1-2 years or if symptoms develop because patients may develop hypothyroidism at a later age.

Glucose metabolism

Abnormalities of glucose metabolism, including overt diabetes mellitus, are more common than in unaffected children.

Urinalysis for glucose should be performed at each follow-up visit with patients taking oxandrolone or human growth hormone.

Continuing care

As routine health maintenance, patients with Turner syndrome should have blood urea nitrogen (BUN), creatinine, fasting blood sugar (FBS) or hemoglobin A1C, fasting lipids, liver enzymes, free thyroxine (T4), and TSH levels measured annually after childhood.


Signs of excess androgens are generally absent. 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. 

Diabetes mellitus testing

A prospective study of 113 Italian patients with Turner syndrome showed that diabetes mellitus is a common finding, suggesting it is specific to the syndrome. The study also demonstrated that oral glucose tolerance test is a more sensitive test than HbA1c for the diagnosis of diabetes mellitus in Turner syndrome

Imaging Studies:


At diagnosis, perform ultrasonography of the kidneys and renal collecting system.

Annual urine cultures and measurement of BUN and creatinine levels are recommended for those patients with abnormalities of the renal collecting system that predispose to obstruction.


Upon diagnosis, evaluate the heart and aorta with echocardiography, magnetic resonance imaging (MRI), or both.

Measure 4-limb blood pressures, because of 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.

A complete cardiovascular evaluation should be completed prior to attempting assisted reproduction. 

Bone age

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, and growth hormone is contraindicated if epiphyses are fused.

Bone density

Osteoporosis is common but may be overdiagnosed in short individuals. 

Measure bone density initially in adults and 3 years later.





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