You are on page 1of 12


In 1938, Henry Turner first described Turner syndrome, which is one of the most common chromosomal abnormalities.[1] More than 95% of adult women with Turner syndrome exhibit short stature and infertility. Examples of manifestations of Turner syndrome are shown in the images below.

A patient with Turner syndrome is shown. This posterior view shows a low hairline and a shield-shaped chest. Note the narrow hip development.

Lymphedema of the feet in an infant is shown. The toes have

the characteristic sausagelike appearance. in Turner syndrome. Note U-shaped cross section.

Hyperconvex nails

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.


United States The frequency is approximately 1 in 2000 live-born female infants.[2] As many as 15% of spontaneous abortions have a 45,X karyotype. International The incidence is the same as in the United States. No known ethnic or racial factors influence frequency.

Mortality may be increased in the neonatal period because of hypoplastic left heart[3] 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. 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. In a Danish study, the overall risk of autoimmune disease among women with Turner syndrome was twice that among Danish women in general.[4] Risk for autoimmune diseases more often found in males was notably high. For individual diseases, associations were strongest for Hashimoto thyroiditis, a condition more common in females, and type 1 diabetes mellitus.

No racial or ethnic predilections are known.

Turner syndrome only occurs in females.[5] Noonan syndrome, sometimes inappropriately called male Turner syndrome, can occur in males or females. It is an autosomal dominant genetic disorder and is not a chromosomal disorder. It is unrelated to Turner syndrome.

As a chromosomal disorder, Turner syndrome is present at conception or following the first cell division and remains throughout life. Gonadotropin levels, particularly folliclestimulating hormone (FSH) levels, may be elevated at birth, although not reliably enough for

use in neonatal screening.[6] They are gradually suppressed by about age 4 years, only to rise to menopausal levels after age 10 years.[7

Older individuals may have a history of swollen hands and feet at birth. Children usually present with short stature, but some girls younger than 11 years have heights within the normal range for girls without Turner syndrome.[8] Although the presence of other features may increase the index of suspicion, a karyotype is indicated in any girl with unexplained short stature. In older adolescents and adults, presenting symptoms usually involve issues of puberty and fertility as well as short stature. Adrenarche, the beginning of pubic hair growth, occurs at a normal age and is not an indication that puberty will progress normally. Breast development is absent when ovarian failure occurs before puberty, but pubic hair growth is normal. Up to 13% of girls with Turner syndrome have spontaneous breast development[9] or menses; some of these are XO/XX mosaics, with normal gonadotropin responses to luteinizing hormone releasing hormone (LHRH).[10] Diagnosis should be considered in individuals with primary or secondary amenorrhea and in adult women with unexplained infertility, particularly when such individuals also are short in stature. Approximately 30% of girls with Turner syndrome have some spontaneous pubertal development.

Approximately 95% of individuals with Turner syndrome have both short stature and signs of ovarian failure upon physical examination.

Short stature: In adults, short stature is due to both a slightly slower growth rate in childhood and to an essentially absent adolescent growth spurt. Before age 11 years, some girls have height and growth rates that are well within the normal range, but heights are below the 50th percentile for girls without Turner syndrome.[8] Dental: A high arched palate suggests the diagnosis. Patients may have dental crowding or malocclusion. Ovarian failure: Suspect ovarian failure in girls who have no breast development by age 12 years or who have not started menses by age 14 years. Elevated levels of luteinizing hormone (LH) and FSH confirm ovarian failure. Pubic hair: Pubic hair development is normal. Nails: Many patients have hypoplastic or hyperconvex nails. Although these are not a clinical problem, they are rarely seen in other patients. Nevi: Excessive numbers of nevi, when compared to other family members, are common. These may be removed if rubbed or irritated by clothing. Webbed neck: Lymphedema in utero can cause a broad neck and a low or indistinct hairline. Cubitus valgus (increased carrying angle): This is a common skeletal anomaly in girls due to abnormal development of the trochlear head. Other anomalies include Madelung deformities and short fourth and fifth metacarpals and metatarsals.

Short fourth metacarpal or metatarsal: Although this finding is of minimal clinical significance, it can be a clue to the presence of Turner syndrome. Shield chest: The chest appears to be broad with widely spaced nipples. This may be caused in part by a short sternum. Lymphedema: Lymphedema may be present at any age and is one finding that can suggest Turner syndrome on fetal ultrasonography. Lymphedema is the cause of other anomalies, such as the webbed neck and low posterior hairline. In infants, the combination of dysplastic or hypoplastic nails and lymphedema gives a characteristic sausagelike appearance to the fingers and toes. Eye: Ptosis, strabismus, amblyopia, and cataract s are more common in girls with Turner syndrome. Epicanthal folds can be present. Red-green color blindness is an Xlinked condition and is believed to occur in girls with Turner syndrome as commonly as it does in males. Ears: Serous otitis media is more common, probably due to poor anatomic drainage of the middle ear, which may be associated with a high-arched palate.[11] The auricles may be posteriorly rotated or low set as a result of lymphedema. 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. Hip dislocation: Infants have a higher incidence of congenital hip dislocation. They should be evaluated clinically and referred for further treatment, if needed. Scoliosis: This occurs in 10% of adolescent girls with Turner syndrome and may contribute to short stature. Scoliosis screening is essential. Hypertension: Blood pressure elevations may be caused by coarctation of the aorta or renal anomalies but often occur even in the absence of such findings. Blood pressure should be routinely monitored and measured at each medical visit. Four-limb blood pressures should also be evaluated because of the concern of coarctation. Murmurs: Cardiovascular malformations include hypoplastic left heart[3] , coarctation of the aorta, bicuspid aortic valve, and aortic dissection in adulthood. All individuals should have an initial evaluation and periodic follow-up care from a cardiologist.[12] Evaluation prior to initiation of estrogen therapy or assisted reproduction is strongly recommended. Thyroid: As many as half of patients have positive antithyroid antibodies, and 10-30% develop hypothyroidism.[13] This 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. Prenatal signs o Most concepti with a 45,X karyotype spontaneously abort. Most, if not all, of those who survive to birth are suspected to have mosaicism for a normal cell line. o Turner syndrome may be prenatally diagnosed by amniocentesis or chorionic villous sampling. Obtain a karyotype by one of these methods if ultrasonography of a fetus reveals a nuchal cystic hygroma,[14, 15] horseshoe kidney, left-sided cardiac anomalies, or nonimmune fetal hydrops. A postnatal karyotype may be performed instead of amniocentesis or chorionic villus sampling and is also recommended if the human chorionic gonadotropin (HCG), estradiol, or alpha-fetoprotein (AFP) level is elevated during pregnancy. o Neonatal pedal edema suggests a diagnostic evaluation for Turner syndrome.

The diagnosis of Turner syndrome requires the presence of typical phenotypic features and the complete or partial absence of a second sex chromosome.

Advanced maternal age is not associated with an increased incidence. In patients with a single X chromosome, the chromosome is of maternal origin in two thirds of cases. Many of the features of Turner syndrome, including the short stature, are due to the lack of a second SHOX gene, which is on the X chromosome.[16]

Laboratory Studies

A standard 30 cell Karyotype is required for diagnosis of Turner syndrome, in oder to exclude mosaicism.[17] 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.[5]

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.[18] 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.[7] 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,[13] 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. Glucose tolerance tests should not be used as a screening test. Obesity should be avoided. Screening for diabetes mellitus is best performed by obtaining a hemoglobin A1c or fasting glucose level. 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 BUN, creatinine, fasting blood sugar (FBS) or hemoglobin A1C, fasting lipids, liver enzymes, free thyroxine (T4), and TSH levels measured annually after childhood. Virilization: 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.[18]

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.


Perform echocardiography, or MRI examination of the heart and aorta, 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. A complete cardiovascular evaluation should be completed prior to attempting assisted reproduction.[19]

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.

Other Tests
Audiology is indicated in patients with Turner syndrome.

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. More frequent testing is needed in children with repeated otitis media. Adults should also have a hearing evaluation at least once with further testing later if hearing loss is suspected

Medical Care
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.[20] In childhood, growth hormone therapy is standard to prevent short stature as an adult.[21, 22, 23] 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.[24] 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 .[9] 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.[17] Transdermal estrogens are associated with physiologic estrogen levels[25] , and may be preferred treatment, if tolerated.[17] Growth hormone may have long-term favorable effects on lipids, even after it is discontinued.[26] Androgen replacement therapy is not the standard of care[17] , but may have favorable effects.[27]

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.



During childhood and adolescence, patients should visit a pediatric endocrinologist at regular intervals. Attention should be paid to growth and development, thyroid status, and osteoporosis prevention with growth hormone, estrogens, and progestins. Patients on growth hormone should be seen every 3-6 months.


A cardiologist should evaluate all patients at diagnosis. Patients with systemic hypertension or aortic valve anomalies are at higher risk for aortic dissection. Patients found to have significant anomalies should have long-term follow-up care and possibly SBE prophylaxis. Because of the risks of aortic root dilatation and mortality due to aortic dissection, cardiac evaluation (including echocardiography) may be worthwhile every 5 years, even in patients with normal findings on initial cardiovascular examination. Patients contemplating pregnancy should have a complete cardiovascular evaluation prior to attempting assisted reproduction or conception. Patients with a bicuspid aortic valve, coarctation of the aorta, or dilation of the aorta have a higher risk of dissecting aortic aneurysm or rupture.

Nephrologist or urologist

Almost a third of patients have renal anomalies that may require evaluation and follow-up care by a nephrologist. At a minimum, such patients should have a yearly urine culture and an annual measurement of BUN and creatinine levels. Girls with horseshoe kidneys have an increased risk of Wilms tumor. Patients with horseshoe kidneys should have renal ultrasound examinations every 4-6 months until the age 8 years and every 6-12 months thereafter.


Overall psychological health is good, but specific perceptual weaknesses or learning disabilities may be present. Assessment of intelligence, learning ability, motor skills, and social maturity should be made prior to enrollment in kindergarten.[28] Problems with math and with visual spatial skills (eg, map reading) are common. Attention deficit hyperactivity disorder is more common in girls with Turner syndrome than in girls in general. Intelligence is usually normal, but individuals with ring chromosomes may have impaired intelligence. As with any chronic illness, attention should be paid to fostering healthy socialization and to appropriate career and vocational planning.


Turner syndrome is not an inherited disorder, and the recurrence risk is low. Because of infertility, the syndrome is rarely passed to offspring.

Consultation is helpful when the condition is diagnosed in utero or when Turner syndrome is suspected in the setting of a normal peripheral blood karyotype. Patients should be tested for the presence of Y-chromosomal material using a Ycentromeric probe.

Dietary requirements are similar to those of other children or adults.

Both short stature and ovarian failure are risk factors for osteoporosis, and care should be taken to ensure adequate daily intake of calcium (1.0-1.5 g) and vitamin D (at least 400 IU). Patients should avoid obesity because it increases already high risks of hypertension and insulin resistance. Patients with short stature require fewer calories than those of normal height.

Physical activity should be encouraged as prevention for obesity and osteoporosis. Eligibility for competitive sports should be established by a cardiologist after a comprehensive evaluation.[5]

Human growth hormone

Class Summary
These agents are the primary treatment for short stature. They stimulate growth of linear bone, skeletal muscle, and organs. View full drug information

Somatotropin (Nutropin, Genotropin, Humatrope, Norditropin, Saizen, TevTropin)

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").

Anabolic steroids
Class Summary
This is an adjuvant for growth hormone therapy.

View full drug information

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.

Thyroid replacement therapies

Class Summary
These agents are used for treatment of hypothyroidism. View full drug information

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.

Estrogen replacement therapies

Class Summary
Almost all individuals require estrogen replacement. Estrogen is usually started at chronologic age 12 years or older. Adults usually require cyclic therapy with both estrogen and progestin. Transdermal or parenteral estrogen may be useful in limiting some adverse effects of estrogen therapy.


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.

Antihypertensive agents
Class Summary

These products are used to control hypertension and to ultimately prevent complications such as aortic dissection. The 2 most common class of medications used for these purposes in pediatric patients are beta-blockers and ACE inhibitors. Propranolol is an example of one of the beta-blockers used in pediatrics, whereas captopril is an example of an ACE inhibitor. Additional drug recommendations for patients aged 1-17 years may be found in The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. For neonatal doses, see the eMedicine article Neonatal Hypertension. For pediatric doses, see the eMedicine article Hypertension. View full drug information

Propranolol (Inderal)

Has membrane-stabilizing activity and decreases automaticity of contractions. View full drug information

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Vitamins and minerals

Class Summary
Osteoporosis is common and is a major cause of morbidity in adults. Treatment is the same as for other adult women with osteoporosis. Monitor diet and ensure an intake of at least 1 g/d of calcium and 400 IU/d of vitamin D. Treatment with growth hormone and estrogen are also important in the prevention of osteoporosis later in life. View full drug information

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.

Calcium salts (acetate, carbonate, chloride, gluconate)


Supplemental source of dietary calcium. Calcium carbonate is 40% elemental calcium.

Overall prognosis for patients with Turner syndrome is good.

Even with growth hormone therapy, most individuals are shorter than average.[29] Turner syndrome is not a cause of mental retardation.[30] Life expectancy is slightly shorter than average but may be improved by attention to associated chronic illnesses, such as obesity and hypertension.[31] Almost all individuals are infertile, but pregnancy with donor embryos is possible.[32]

Patient Education
For excellent patient education resources, please refer to eMedicine's Amenorrhea article, Endocrine System Center, and Women's Health Center. All these materials may be printed free of charge.