Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a

female Female ( symbol: ♀) is the sex of an organism that produces the large non-motile ova (egg cells), the type of gamete (sex cell) that fuses with the male gamete during sexual reproduction. A female has larger gametes than a male. Females ...

is partially or completely missing an

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...

. Signs and symptoms vary among those affected. Often, a short and

webbed neck A webbed neck, or pterygium colli, is a congenital skin fold that runs along the sides of the neck down to the shoulders. There are many variants. Signs and symptoms On babies, webbed neck may look like loose folds of skin on the neck. As the ch ...

low-set ears Low-set ears are a clinical feature in which the ears are positioned lower on the head than usual. They are present in many congenital conditions. Low-set ears are defined as outer ears positioned two or more standard deviations lower than the p ...

, low hairline at the back of the neck,

short stature Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ' ...

, and

swollen Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...

hands and feet are seen at birth. Typically, those affected do not develop menstrual periods, or

breasts The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and sec ...

without hormone treatment and are unable to have children without reproductive technology.

Heart defects A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

, and low thyroid hormone occur in the disorder more frequently than average. Most people with Turner syndrome have normal intelligence; however, many have problems with spatial visualization that may be needed in order to learn mathematics. Vision and hearing problems also occur more often than average. Turner syndrome is not usually inherited; rather, it occurs during formation of the

reproductive cells A gamete (; , ultimately ) is a haploid cell that fuses with another haploid cell during fertilization in organisms that reproduce sexually. Gametes are an organism's reproductive cells, also referred to as sex cells. In species that produce ...

in a parent or in early cell division during development. No environmental risks are known, and the

mother's age Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.mosaicism Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized ...

. In these cases the symptoms are usually fewer, and possibly none occur at all. Diagnosis is based on physical signs and

genetic test Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, o ...

ing. No cure for Turner syndrome is known. Treatment may help with symptoms. Human growth hormone injections during childhood may increase adult height. Estrogen replacement therapy can promote development of the

and hips. Medical care is often required to manage other health problems with which Turner syndrome is associated. Turner syndrome occurs in between one in 2,000 and one in 5,000 females at birth. All regions of the world and cultures are affected about equally. Generally people with Turner syndrome have a shorter life expectancy, mostly due to heart problems and diabetes. American endocrinologist Henry Turner first described the condition in 1938. In 1964, it was determined to be due to a chromosomal abnormality.

Presentation

Turner syndrome has a number of physical and psychological impacts, including

, heart defects, neck webbing, delayed or absent puberty, and infertility. The

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

of Turner syndrome is affected by

mosaicism Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized ...

, where cell lines with a single sex chromosome are combined with those with multiple. Around 40%–50% of cases of Turner syndrome are true "monosomy X" with a 45,X0 karyotype, while the remainder are mosaic for another cell line, most commonly 46,XX, or have other structural abnormalities of the X chromosome. The classic features of Turner syndrome, while distinctive, may be rarer than previously thought; incidental diagnosis, such as in

biobank A biobank is a type of biorepository that stores biological samples (usually human) for use in research. Biobanks have become an important resource in medical research, supporting many types of contemporary research like genomics and personalize ...

samples or prenatal testing for older mothers, finds many girls and women with few traditional signs of Turner syndrome.

Physiological

Height

Relationship between chromosome X dosage in 45, X and 47, XXX females for quantitative traits

Turner syndrome is associated with short stature. The mean adult height of women with Turner syndrome without growth hormone therapy is around shorter than the mean of women in the general population. Mosaicism affects height in Turner syndrome; a large population sample drawn from the

UK Biobank UK Biobank is a large long-term biobank study in the United Kingdom (UK) which is investigating the respective contributions of genetic predisposition and environmental exposure (including nutrition, lifestyle, medications etc.) to the developme ...

found women with 45,X0 karyotypes to have an average height of , while those with 45,X0/46,XX karyotypes averaged . The strength of the association between Turner syndrome and short stature is such that

idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. From Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approximately "a disease of its own kin ...

short stature alone is a major diagnostic indication. Growth delay in Turner syndrome does not begin at birth; most

neonate An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

s with the condition have a

birth weight Birth weight is the body weight of a baby at its birth. The average birth weight in babies of European descent is , with the normative range between . On average, babies of South Asian and Chinese descent weigh about . As far as low birth weigh ...

in the lower end of the normal range. Height begins to lag in toddlerhood, with a delayed growth velocity becoming apparent as early as 18 months. When girls with Turner syndrome begin school, their height is usually still not remarkably unusual; marked short stature becomes obvious in mid-childhood. In undiagnosed preadolescents and adolescents, growth delay may be mistaken for a side effect of delayed puberty and improperly treated. Short stature in Turner syndrome and its counterpoint, tall stature in sex chromosome polysomy conditions such as

Klinefelter syndrome Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are sub ...

XYY syndrome XYY syndrome, also known as Jacobs syndrome, is an aneuploid genetic condition in which a male has an extra Y chromosome. There are usually few symptoms. These may include being taller than average, acne, and an increased risk of learning disa ...

, and trisomy X, is caused by the short-stature homeobox gene on the X and Y chromosomes. The absence of a copy of the ''SHOX'' gene in Turner's inhibits skeletal growth, resulting both in overall short stature and in a distinctive pattern of skeletal malformations including micrognathia (small chin), cubitus valgus (abnormal forearm angles), and short fingers. When Turner syndrome is diagnosed in early life,

growth hormone therapy Growth hormone therapy refers to the use of growth hormone (GH) as a prescription medication—it is one form of hormone therapy. Growth hormone is a peptide hormone secreted by the pituitary gland that stimulates growth and cell reproduction. I ...

can decrease the degree of short stature. The use of growth hormone therapy in Turner's originated from a series of studies in the 1980s finding it to substantially increase the height of treated girls, compared to prior adult height predictions and Turner's growth charts; treatment with human growth hormone appears to increase expected adult height by approximately from an otherwise expected norm of –. In some cases

oxandrolone Oxandrolone, sold under the brand names Oxandrin and Anavar, among others, is an androgen and anabolic steroid (AAS) medication which is used to help promote weight gain in various situations, to help offset protein catabolism caused by long-ter ...

, a steroid with a relatively mild masculinizing effect, may be used alongside growth hormone. The addition of oxandrolone to a Turner's treatment regimen adds around to the final height. Oxandrolone is used particularly often in girls diagnosed later in their growth period, due to the reduced impact of growth hormone alone in this population. However, oxandrolone use runs the risk of delayed breast development, voice deepening, increased body hair, or clitoromegaly. The effects of growth hormone therapy are at their strongest during the first year of treatment and taper off over time.

Physical features

Preoperative webbed neck in Turner syndrome

In addition to short stature, Turner syndrome is associated with a number of characteristic physical features. These include a webbed neck, a low hairline, a small chin and jaw, a high-arched palate, and a broad chest with wide-spaced nipples.

Lymphedema Lymphedema, also known as lymphoedema and lymphatic edema, is a condition of localized swelling caused by a compromised lymphatic system. The lymphatic system functions as a critical portion of the body's immune system and returns interstitial fl ...

(swelling) of the hands and feet is common at birth and sometimes persistent throughout the lifespan. Some Turner's stigmata, such as cubitus valgus and shortened fingers, are related to ''SHOX'' gene dosage effects. A number of the external manifestations of Turner syndrome are focused on the limbs, hands, and feet. Lymphedema at birth is one of the classic features of the syndrome; though it often resolves during toddlerhood, recurrence in later life is frequent, often without apparent cause. Cases where the retained X chromosome was inherited from the mother more often experience lymphedema than those where it was from the father. As a consequence of lymphedema's effects on nail anatomy, females with Turner syndrome frequently have small

hypoplastic Hypoplasia (from Ancient Greek :wikt:ὑπό, ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ. Shortened metacarpal bones, particularly the fourth metacarpal, are a frequent finding. The body shape of individuals with Turner syndrome is frequently quite broad and stocky, as the growth deficiency is more pronounced in the length of bones than in their width. Scoliosis is common in Turner syndrome, and is seen in 40% of girls without growth hormone treatment. Facial features associated with Turner syndrome include prominent ears, a low hairline, a webbed neck, a small chin with dental

malocclusion In orthodontics, a malocclusion is a misalignment or incorrect relation between the teeth of the upper and lower dental arches when they approach each other as the jaws close. The English-language term dates from 1864; Edward Angle (1855-19 ...

, and downslanting

palpebral fissure The palpebral fissure is the elliptic space between the medial and lateral canthi of the two open eyelids. In simple terms, it is the opening between the eyelids. In adult humans, this measures about 10 mm vertically and 30 mm horizontally. Va ...

s (the opening between the eyelids). These are thought to be related to lymphedema during the fetal period, specifically to the presence and resorption of excess fluids in the head and neck region. Neck webbing is a particularly distinctive trait of Turner syndrome, leading to many neonatal diagnoses. The underlying etiology of neck webbing is related to prenatal blood flow issues, and even in populations without Turner's has broad health consequences; the rate of congenital heart disease in webbed neck is 150-fold higher than in the general population, while the feature is also associated with reduced height and minor developmental impairments. Some women with Turner syndrome have premature facial wrinkling. Acne is less common in teenage girls and women with Turner syndrome, though the reasons why are unclear. Baby Turner

Other physical features connected to the condition include long eyelashes, sometimes including an additional set of eyelashes, and unusual

dermatoglyphics Dermatoglyphics (from Ancient Greek ''derma'', "skin", and ''glyph'', "carving") is the scientific study of fingerprints, lines, mounts and shapes of hands, as distinct from the superficially similar pseudoscience of palmistry. Dermatoglyphics a ...

(fingerprints). Some women with Turner's report being unable to create fingerprint passwords due to hypoplastic dermatoglyphics. Unusual dermatoglyphics are common to chromosome anomalies and in the case of Turner's may be a consequence of fetal lymphedema. Keloid scars, or raised hypertrophic scars growing beyond the boundaries of the original wound, are potentially associated with Turner syndrome; however, the association is underresearched. Though traditional medical counselling on the topic urges conservatism about elective procedures such as ear piercing due to the risk of severe scarring, the actual consequences are unclear. Keloids in Turner syndrome are particularly frequent following surgical procedures to reduce neck webbing. Turner syndrome has been associated with unusual patterns of hair growth, such as patches of short and long hair. Armpit and pubic hair is often sparse, while arm and leg hair is often thick. Though armpit hair is reduced in amount and thickness, the pattern in which it is implanted in the skin is as in men, rather than as in women.

Cardiac

The basic anatomy of the bicuspid aortic valve

Approximately half of individuals with Turner syndrome have

congenital heart defect A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascul ...

s. CHDs associated with Turner syndrome include

bicuspid aortic valve Bicuspid aortic valve (aka BAV) is a form of heart disease in which two of the leaflets of the aortic valve fuse during development in the womb resulting in a two-leaflet (bicuspid) valve instead of the normal three-leaflet (tricuspid) valve. BA ...

s (30%), coarctation of the aorta (15%), and abnormalities of the arteries in the head and neck. A rare but potentially fatal complication of heart defects in Turner syndrome is

aortic dissection Aortic dissection (AD) occurs when an injury to the innermost layer of the aorta allows blood to flow between the layers of the aortic wall, forcing the layers apart. In most cases, this is associated with a sudden onset of severe chest or ...

, where the inner layer of the

aorta The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes o ...

tears open. Aortic dissection is six times as common in females with Turner syndrome as the general population and accounts for 8% of all deaths in the syndrome. The risk is substantially increased for individuals with bicuspid aortic valves, who make up 95% of patients with aortic dissection compared to 30% of all Turner's patients, and coarctation of the aorta, who make up 90% and 15% respectively. Coronary artery disease onsets earlier in life in women with Turner syndrome compared to controls, and mortality from cardiac events is increased. This is thought to be in part a function of the relationship between Turner syndrome and

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

; women with Turner syndrome have a higher percentage of body fat for their weight than control women, and their short stature makes weight control more difficult. Though coronary artery disease is frequently thought a disease of older adults, young women with Turner syndrome are more likely to develop the disease than their 46,XX peers. Treatment recommendations for women with Turner syndrome and coronary artery disease are as in the general population, but as Turner's increases the risk of type 2 diabetes, women with insulin resistance must weigh up the benefits of

prophylactic Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

or early

statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low ...

treatment with the risk of diabetes.

Internal medicine

Turner syndrome is associated with a broad variety of health considerations, such as liver and kidney issues, obesity, diabetes, and hypertension. Liver dysfunction is common in women with Turner syndrome, with 50%–80% having elevated

liver enzymes Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin tim ...

. Non-alcoholic fatty liver disease is increased in prevalence in Turner syndrome, likely related in part to both conditions' associations with obesity. Hepatic vascular diseases are also seen in the syndrome as an aspect of Turner syndrome's broader vascular and cardiac impacts.

Primary biliary cholangitis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build ...

is more common in 45,X0 than 46,XX women. An unclear association exists between estrogen replacement therapy and liver dysfunction in Turner syndrome; some studies imply estrogen therapy worsens such conditions, while others imply improvement. Duplicated ureter

Kidney issues, such as

horseshoe kidney Horseshoe kidney, also known as ''ren arcuatus'' (in Latin), renal fusion or super kidney, is a congenital disorder affecting about 1 in 500 people that is more common in men, often asymptomatic, and usually diagnosed incidentally. In this disorder ...

, are sometimes observed in Turner syndrome. Horseshoe kidney, where the kidneys are fused together in a U-shape, occurs in around 10% of Turner's cases compared to less than 0.5% of the general population. A missing kidney is observed in as many as 5% of individuals with Turner syndrome, compared to around 0.1% of the population. A duplicated ureter, where two

ureter The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...

s drain a single kidney, occurs in as much as 20%–30% of the Turner syndrome population. Kidney malformations in Turner syndrome may be more common in mosaicism than in the full 45,X0 karyotype. Serious complications of the kidney anomalies associated with Turner syndrome are rare, although there is some risk of issues such as obstructive uropathy, where the flow of urine from the kidneys is blocked. Women with Turner syndrome are more likely than average to have high blood pressure; as many as 60% of women with the condition are hypertensive. Isolated diastolic hypertension often precedes systolic hypertension in the condition and may develop at a young age. Treatments for hypertension in Turner syndrome are as in the general population. Approximately 25%–80% of women with Turner syndrome have some level of insulin resistance, and a minority develop

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...

. The risk of diabetes in Turner syndrome varies by karyotype and appears to be raised by specific deletions of the short arm of the X chromosome (Xp). One study found that while a relatively low 9% of women with Xq (long arm) deletions had type 2 diabetes, 18% of those with full 45,X0 karyotypes did, as well as 23% with Xp deletions. 43% of women with isochromosome Xq, who both lacked the short arm and had an additional copy of the long arm, developed type 2 diabetes. Though part of the diabetes risk in Turner syndrome is a function of weight control, some is independent; age- and weight-matched women with non-Turner's ovarian failure have a lower diabetes risk than in Turner syndrome. Growth hormone treatment plays an unclear role in diabetes risk, as does estrogen supplementation. The association between Turner syndrome and other diseases, such as cancer, is unclear. Overall, women with Turner syndrome do not appear more likely to develop cancer than women with 46,XX karyotypes, but the specific pattern of what cancers are highest risk seems to differ. The risk of

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

appears lower in Turner's than in control women, perhaps due to decreased levels of estrogen.

Neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in th ...

, a cancer of infancy and early childhood, has been reported in girls with Turner syndrome. Tumours of the nervous system, both the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

and the

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

, are overrepresented amongst cancers in Turner syndrome. Furthermore, about 5.5% of Turner syndrome individuals have an extra, abnormal

small supernumerary marker chromosome A small supernumerary marker chromosome (sSMC) is an abnormal extra chromosome. It contains copies of parts of one or more normal chromosomes and like normal chromosomes is located in the cell's nucleus, is replicated and distributed into each d ...

(sSMC) which consists of part of a Y chromosome. This partial Y chromosome-bearing sSMC may include the '' SRY'' gene located on the p arm of the Y chromosome at band 11.2 (notated as Yp11.2). This gene encodes the

testis-determining factor Sex-determining region Y protein (SRY), or Testis-determining factor (TDF), is a DNA-binding protein (also known as gene-regulatory protein/transcription factor) encoded by the ''SRY'' gene that is responsible for the initiation of male sex d ...

protein (also known as sex-determining region Y protein). Turner syndrome individuals with this ''SRY'' gene-containing sSMC have a very real increased risk of developing gonadal tissue neoplasms such as

gonadoblastoma A gonadoblastoma is a complex neoplasm composed of a mixture of gonadal elements, such as large primordial germ cells, immature Sertoli cells or granulosa cells of the sex cord, and gonadal stromal cells. Gonadoblastomas are by definition benign, ...

s and

in situ ''In situ'' (; often not italicized in English) is a Latin phrase that translates literally to "on site" or "in position." It can mean "locally", "on site", "on the premises", or "in place" to describe where an event takes place and is used in ...

seminoma A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if discovered in ...

s (also termed dysgerminomas to indicate that this tumor has the pathology of the testicular tumor, seminoma, but develops in ovaries). In one study, 34 Turner syndrome girls without overt evidence of these tumors were found at preventative surgery to have a gonadoblastoma (7 cases), dysgerminoma (1 case), or non-specific ''in situ'' gonadal neoplasm (1 case). Turner syndrome girls with this sSMC otherwise have typical features of the Turner syndrome except for a minority who also have

hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...

and/or clitoral enlargement. Surgical removal of the

gonads A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...

has been recommended to remove the threat of developing these sSMC-associated neoplasms. Tuner syndrome individuals with an sSMC that lacks the ''SRY'' gene are not at an increased risk of developing these cancers.

Sensory

Hearing loss is common in Turner syndrome. Though at birth hearing is generally normal, chronic middle ear problems are frequent throughout childhood, which can cause permanent

conductive hearing loss Conductive hearing loss (CHL) occurs when there is a problem transferring sound waves anywhere along the pathway through the outer ear, tympanic membrane (eardrum), or middle ear (ossicles). If a conductive hearing loss occurs in conjunction with ...

. In adulthood, sensorineural hearing loss occurs more often than in 46,XX women and at younger ages; though differing thresholds of hearing loss make it difficult to compare between studies, younger adult women with Turner syndrome are routinely found to have disproportionate rates of hearing issues, with sometimes up to half of women in their 20s and 30s having poor hearing. This hearing loss is progressive; at the age of 40, women with Turner syndrome have equivalent hearing loss to 46,XX women aged 60, on average. Cohort studies imply hearing loss may be more common in women who also have metabolic syndrome. The high prevalence of sensorineural hearing loss in Turner syndrome appears to be related to ''SHOX'' deficiency. Ocular and visual disorders are also increased in prevalence in Turner syndrome. More than half of individuals with Turner syndrome have some form of eye disorder. This may be a consequence of shared genes on the X chromosome in both eye and ovary development. Nearly half of cases have

hyperopia Far-sightedness, also known as long-sightedness, hypermetropia, or hyperopia, is a condition of the eye where distant objects are seen clearly but near objects appear blurred. This blurred effect is due to incoming light being focused behind, i ...

or myopia, usually mild.

Strabismus Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...

, or misalignment of the eye, occurs in around one-fifth to one-third of girls with Turner syndrome. As with strabismus outside the Turner's context, it may be treated with glasses, patching, or surgical correction.

Esotropia Esotropia is a form of strabismus in which one or both eyes turns inward. The condition can be constantly present, or occur intermittently, and can give the affected individual a "cross-eyed" appearance. It is the opposite of exotropia and usual ...

, where the eye turns inwards, is more common than

exotropia Exotropia is a form of strabismus where the eyes are deviated outward. It is the opposite of esotropia and usually involves more severe axis deviation than exophoria. People with exotropia often experience crossed diplopia. Intermittent exotrop ...

, where it turns outwards. Ptosis, or a drooping eyelid, is a common facial manifestation of Turner syndrome; it usually has no appreciable impact on vision, but severe cases may limit visual range and require surgical correction. The rate of red-green colourblindness in Turner syndrome is 8%, the same as in men. This is due to red-green colourblindness being an

X-linked recessive X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily homozygous for the gene mutation because they have one X and one Y ...

condition; in people with a single X chromosome, whether normal males or Turner females, only a single mutated X is necessary for symptoms. Red-green colourblindness may be underdiagnosed in the Turner context, as the rarity of the condition in females reduces the likelihood of screening, and practitioners may not connect that the karyotype of Turner syndrome increases the risk from the female baseline.

Autoimmune

Women with Turner syndrome are two to three times as likely to develop

autoimmune disorder An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly ...

s as the general population. Specific autoimmune disorders linked to Turner syndrome include Hashimoto's disease,

vitiligo Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmen ...

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

and

psoriatic arthritis Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. Th ...

alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scar ...

, and

celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

. Inflammatory bowel disease is also common, while the prevalence of

type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar ...

is unclear, though appears increased. Thyroid disease is common in Turner syndrome. Hypothyroidism is prevalent; 30%–50% of women with Turner syndrome have Hashimoto's disease, where the thyroid gland is slowly destroyed by an autoimmune reaction. By age 50, half of women with Turner syndrome have subclinical or clinical hypothyroidism.

Hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidis ...

and Graves' disease are also increased in prevalence, though more modestly. The Turner's presentation of hyperthyroidism is as in the general population, while the presentation of hypothyroidism is often atypical, with a mild early presentation yet a more severe progression. Women with isochromosome Xq are more likely to develop autoimmune thyroid disease than women with other forms of Turner syndrome. The risk of irritable bowel syndrome is increased around fivefold in Turner syndrome, and that of

ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...

around fourfold. Celiac disease is also increased in prevalence, with around 4%–8% of Turner's patients having comorbid celiac disease compared to 0.5%–1% of the general population. Diagnosis of such conditions is difficult due to their nonspecific early symptoms. In the Turner's context, diagnosis may in particular be missed due to growth delay; such conditions cause growth delay and failure to thrive when they onset in childhood, but as girls with Turner syndrome already have such delay, symptoms may be overlooked and ascribed to the original condition.

Alopecia areata Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. Often, it results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are pos ...

, or recurrent patchy hair loss, is three times as common in Turner syndrome as the general population. Alopecia in the Turner syndrome context is frequently treatment-resistant, also seen in other chromosome aneuploidies such as

Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...

. Psoriasis is common in Turner syndrome, although the precise prevalence is unclear. Turner's psoriasis may be related to growth hormone treatment, as psoriasis as a side effect of such therapies has been reported in patients without the karyotype. Psoriasis may progress to

, and this progression may be more common in Turner syndrome. Vitiligo has been reported in conjunction with Turner syndrome, but the risk is unclear and may be a side effect of increased clinical attention to autoimmune disease in this population.

Puberty

Histological sections of ovarian cortex from patients with TS

Puberty is delayed or absent in Turner syndrome. A 2019 literature review found that 13% of women with a 45,X0 karyotype could expect to experience spontaneous

thelarche Thelarche, also known as breast budding, is the onset of secondary breast development, often representing the beginning of pubertal development. It is the stage at which male and female breasts differentiate due to variance in hormone levels; howe ...

(breast development), while 9% would undergo spontaneous menarche (beginning of menstruation). These numbers were higher in women with mosaic Turner's; 63% with 45,X0/46,XX karyotypes experienced spontaneous thelarche and 39% spontaneous menarche, while 88% with 45,X0/47,XXX (the presence of a trisomy X cell line) experienced spontaneous thelarche and 66% spontaneous menarche. Unexpectedly, women with Y-chromosome cells also had increased rates of thelarche and menarche compared to the 45,X0 baseline, at 41% and 19%. However, few women with trisomy X or Y-chromosome cell lines were covered in the review, impeding extrapolation from these results. 6% of women with Turner syndrome have regular menstrual cycles; the rest experience primary or secondary

amenorrhea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...

or other menstrual dysfunction. In girls with Turner syndrome who do not experience spontaneous puberty, exogenous estrogen is used to induce and maintain feminization. Estrogen replacement is recommended to begin at around age 11–12, although some parents prefer to delay the induction of puberty in girls with lower social and emotional preparedness. The dose of estrogen in induced puberty begins at 10% of adult estrogen levels and is steadily increased at six-month intervals, with a full adult dose attained two to three years after the beginning of treatment. Estrogen replacement may interfere with growth hormone therapy, due to the closing effects of estrogen on growth plates; individuals must weigh up their preferences for taller height versus greater feminization.

Fertility

Women with Turner syndrome are infertile. Only 2%–5% are capable of pregnancy without fertility treatment, most with mosaic karyotypes. Early in gestation, fetuses with Turner syndrome have a normal number of

gamete A gamete (; , ultimately ) is a haploid cell that fuses with another haploid cell during fertilization in organisms that reproduce sexually. Gametes are an organism's reproductive cells, also referred to as sex cells. In species that produce ...

s in their developing ovaries, but this starts decreasingly rapidly as early as 18 weeks of pregnancy; by birth, girls with the condition have markedly reduced follicular counts. Women with Turner syndrome who wish to raise families but are incapable of conception with their own

oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The femal ...

s have the options of adoption or of pregnancy with donor eggs; the latter has a comparable success rate to donor pregnancy in women with 46,XX karyotypes. Pregnancy in Turner syndrome is inherently high-risk; the maternal death rate is 2%. Usually, estrogen replacement therapy is used to spur the growth of secondary sexual characteristics at the time when puberty should onset. While very few women with Turner syndrome menstruate spontaneously, estrogen therapy requires a regular shedding of the uterine lining ("withdrawal bleeding") to prevent its overgrowth. Withdrawal bleeding can be induced monthly, like menstruation, or less often, usually every three months, if the patient desires. Estrogen therapy does not make a woman with nonfunctional ovaries fertile, but it plays an important role in assisted reproduction; the health of the uterus must be maintained with estrogen if an eligible woman with Turner Syndrome wishes to use IVF (using donated

s). Especially in mosaic cases of Turner syndrome that contains Y-chromosome (e.g. 45,X/46,XY) due to the risk of development of ovarian malignancy (most common is

) gonadectomy is recommended. Turner syndrome is characterized by primary

amenorrhoea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of mense ...

, premature ovarian failure (hypergonadotropic hypogonadism), streak gonads and infertility (however, technology (especially oocyte donation) provides the opportunity of pregnancy in these patients). Failure to develop secondary sex characteristics (sexual infantilism) is typical.

Cognition

Neurodevelopmental

Individuals with Turner syndrome have normal intelligence.

Verbal IQ The Wechsler Adult Intelligence Scale (WAIS) is an IQ test designed to measure intelligence and cognitive ability in adults and older adolescents. The original WAIS (Form I) was published in February 1955 by David Wechsler, as a revision of the ...

is usually higher than performance IQ; one review of thirteen studies found an average verbal IQ of 101 compared to an average performance IQ of 89. People with Turner syndrome have normal intelligence, and demonstrate relative strengths in verbal skills, but may exhibit weaker nonverbal skills – particularly in arithmetic, select visuospatial skills, and processing speed. Turner syndrome does not typically cause

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...

or impair cognition. However, learning difficulties are common among women with Turner syndrome, particularly a specific difficulty in perceiving spatial relationships, such as

nonverbal learning disorder Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by core deficits in visual-spatial processing in the presence of intact verbal ability. Additional diagnostic criteria include Average to Superior verbal intell ...

. This may also manifest itself as a difficulty with motor control or with mathematics. While it is not correctable, in most cases it does not cause difficulty in daily living. Most Turner syndrome patients are employed as adults and lead productive lives. Also, a rare variety of Turner syndrome, known as "Ring-X Turner syndrome", has about a 60% association with intellectual disability. This variety accounts for around 2–4% of all Turner syndrome cases.

Psychological

Social difficulties appear to be an area of vulnerability for young women. Counseling affected individuals and their families about the need to carefully develop social skills and relationships may prove useful in advancing social adaptation. Women with Turner syndrome may experience adverse psychosocial outcomes which can be improved through early intervention and the provision of appropriate psychological and psychiatric care. Genetic, hormonal, and medical problems associated with Turner syndrome are likely to affect psychosexual development of female adolescent patients, and thus influence their psychological functioning, behavior patterns, social interactions, and learning ability. Although Turner syndrome constitutes a chronic medical condition, with possible physical, social, and psychological complications in a woman's life, hormonal and estrogen replacement therapy, and assisted reproduction, are treatments that can be helpful for Turner syndrome patients and improve their quality of life. Research shows a possible association between age at diagnosis and increased substance use and depressive symptoms.

Prenatal

Despite the excellent postnatal prognosis, 99% of Turner syndrome conceptions are thought to end in miscarriage or stillbirth, and as many as 15% of all spontaneous abortions have the 45,X karyotype. Among cases that are detected by routine amniocentesis or chorionic villus sampling, one study found that the prevalence of Turner syndrome among tested pregnancies was 5.58 and 13.3 times higher, respectively, than among live neonates in a similar population.

Cause

Turner syndrome is caused by the absence of one complete or partial copy of the X chromosome in some or all the cells. The abnormal cells may have only one X (

monosomy Monosomy is a form of aneuploidy with the presence of only one chromosome from a pair. Partial monosomy occurs when a portion of one chromosome in a pair is missing. Human monosomy Human conditions due to monosomy: * Turner syndrome – People wit ...

) (45,X) or they may be affected by one of several types of partial monosomy like a deletion of the short

p arm In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total ...

of one X chromosome (46, X,del(Xp)) or the presence of an isochromosome with two q arms (46,X,i(Xq)) Turner syndrome has distinct features due to the lack of

pseudoautosomal region The pseudoautosomal regions, PAR1, PAR2, are homologous sequences of nucleotides on the X and Y chromosomes. The pseudoautosomal regions get their name because any genes within them (so far at least 29 have been found for humans) are inherited ...

s, which are typically spared from X-inactivation. In mosaic individuals, cells with X monosomy (45,X) may occur along with cells that are normal (46,XX), cells that have partial monosomies, or cells that have a Y chromosome (46,XY). The presence of mosaicism is estimated to be relatively common in affected individuals (67–90%). The (46,X,i(Xq) isochromosome in the Turner syndrome is classified as an

(sSMC). Two of the types of sSMCs in this syndrome contain parts of the genetic material from either an X or, much less frequently, Y chromosome and may or may not contain an '' XIST'' gene. In normal females, the ''XIST'' gene occurs on the X chromosome inherited from her mother but not on the X chromosome inherited from her father. The gene is not present on Y chromosomes and in normal females resides on and functions to inactivate many of the genes located on its own maternal but not the father's X chromosome. Turner syndrome females with (46,X,i(Xq) sSMC consisting of a partial X chromosome that does not contain the ''XIST'' gene express at least some of this sSMC's genetic material and therefore contain excesses of this material. In consequence, they have a more serious form of the Turner syndrome that ranges form moderately severe to extremely severe. The extremely severe cases have

anencephaly Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube ...

(absence of a major portion of the brain, skull, and scalp), agenesis of the corpus callosum (lack of the thick tract of nerve fibers that connect the left and right cerebral hemispheres), and complex heart deformities. Individuals with Turner syndrome that have partial X chromosome containing(46,X,i(Xq) sSMCs that have the ''XIST'' gene do not express this sSMC's genetic material and do not have the more severe manifestations of the syndrome.

Inheritance

In the majority of cases where monosomy occurs, the X chromosome comes from the mother. This may be due to a

nondisjunction Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis ...

in the father. Meiotic errors that lead to the production of X with p arm deletions or abnormal Y chromosomes are also mostly found in the father. Isochromosome X or

ring chromosome A ring chromosome is an aberrant chromosome whose ends have fused together to form a ring. Ring chromosomes were first discovered by Lilian Vaughan Morgan in 1926. A ring chromosome is denoted by the symbol ''r'' in human genetics and ''R'' in '' ...

X on the other hand are formed equally often by both parents. Overall, the functional X chromosome usually comes from the mother. In most cases, Turner syndrome is a sporadic event, and for the parents of an individual with Turner syndrome the risk of recurrence is not increased for subsequent pregnancies. Rare exceptions may include the presence of a balanced translocation of the X chromosome in a parent, or where the mother has 45,X mosaicism restricted to her germ cells.

Diagnosis

Prenatal

Turner syndrome may be diagnosed by

amniocentesis Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is n ...

or chorionic villus sampling during pregnancy. Usually, fetuses with Turner syndrome can be identified by abnormal

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...

findings (''i.e.'', heart defect, kidney abnormality, cystic hygroma,

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...

). In a study of 19 European registries, 67.2% of prenatally diagnosed cases of Turner syndrome were detected by abnormalities on ultrasound. 69.1% of cases had one anomaly present, and 30.9% had two or more anomalies. An increased risk of Turner syndrome may also be indicated by abnormal triple or quadruple maternal serum screen. The fetuses diagnosed through positive maternal serum screening are more often found to have a mosaic karyotype than those diagnosed based on ultrasonographic abnormalities, and conversely, those with mosaic karyotypes are less likely to have associated ultrasound abnormalities.

Postnatal

Turner syndrome can be diagnosed postnatally at any age. Often, it is diagnosed at birth due to heart problems, an unusually wide neck or swelling of the hands and feet. However, it is also common for it to go undiagnosed for several years, often until the girl reaches the age of puberty and fails to develop typically (the changes associated with puberty do not occur). In childhood, a short stature can be indicative of Turner syndrome. A test called a karyotype, also known as a chromosome analysis, analyzes the chromosomal composition of the individual. This is the test of choice to diagnose Turner syndrome.

Treatment

As a chromosomal condition, there is no cure for Turner syndrome. However, much can be done to minimize the symptoms. While most of the physical findings are harmless, significant medical problems can be associated with the syndrome. Most of these significant conditions are treatable with surgery and other therapies including hormonal therapy. *

Growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...

, either alone or with a low dose of

androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...

, will increase growth and probably final adult height. Growth hormone is approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

for treatment of Turner syndrome and is covered by many insurance plans. There is evidence that this is effective, even in toddlers. A 2019 systematic review comparing effects of adding

to growth hormone treatment to growth hormone alone has found moderate-quality evidence that the addition of oxandrolone leads to an increase in final adult height of girls with Turner syndrome. When the same review assessed the effects of adding Oxandrolone to growth hormone treatment on speech, cognition and psychological status, the results were inconclusive due to very-low quality evidence. * Estrogen replacement therapy such as the

birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progesti ...

, has been used since the condition was described in 1938 to promote development of secondary sexual characteristics. Estrogens are crucial for maintaining good bone integrity, cardiovascular health and tissue health. Women with Turner syndrome who do not have spontaneous puberty and who are not treated with estrogen are at high risk for osteoporosis and heart conditions. * Modern reproductive technologies have also been used to help women with Turner syndrome become pregnant if they desire. For example, a donor egg can be used to create an embryo, which is carried by the Turner syndrome woman. * Uterine maturity is positively associated with years of estrogen use, history of spontaneous menarche, and negatively associated with the lack of current hormone replacement therapy.

Epidemiology

Turner syndrome occurs in between one in 2000 and one in 5000 females at birth. Approximately 99 percent of fetuses with Turner syndrome spontaneously terminate during the first trimester. Turner syndrome accounts for about 10 percent of the total number of spontaneous abortions in the United States.

History

The syndrome is named after Henry Turner, an

endocrinologist Endocrinology (from ''endocrine'' + '' -ology'') is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental events ...

from Illinois, who described it in 1938. In Europe, it is often called ''Ullrich–Turner syndrome'' or ''Bonnevie–Ullrich–Turner syndrome'' to acknowledge that earlier cases had also been described by European doctors Kristine Bonnevie and Otto Ullrich. In Russian and USSR literature, it is called ''Shereshevsky–Turner syndrome'' to acknowledge that the condition was first described as hereditary in 1925 by the Soviet endocrinologist , who believed that it was due to the underdevelopment of the gonads and the

anterior pituitary gland A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...

and was combined with congenital malformations of internal development. The first published report of a female with a 45,X karyotype was in 1959 by Charles Ford and colleagues in Harwell near

Oxford Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to the ...

, and

Guy's Hospital Guy's Hospital is an NHS hospital in the borough of Southwark in central London. It is part of Guy's and St Thomas' NHS Foundation Trust and one of the institutions that comprise the King's Health Partners, an academic health science centre. ...

in London. It was found in a 14-year-old girl with signs of Turner syndrome.

Notes

References

External links

Turner Syndrome at the National Institute of Child Health and Human Development
*
Endocrine and Metabolic Diseases Information Service
{{Authority control Genodermatoses Growth disorders Rare syndromes Wikipedia medicine articles ready to translate Sex chromosome aneuploidies Syndromes affecting stature Syndromes affecting the heart Syndromes affecting the kidneys Intersex variations

Presentation

Physiological

Height

Physical features

Cardiac

Internal medicine

Sensory

Autoimmune

Puberty

Fertility

Cognition

Neurodevelopmental

Psychological

Prenatal

Cause

Inheritance

Diagnosis

Prenatal

Postnatal

Treatment

Epidemiology

History

See also

Notes

References

Further reading

External links