Turner syndrome
Encyclopedia
Turner syndrome or Ullrich-Turner syndrome (also known as "Gonadal dysgenesis") encompasses several conditions in human female
s, of which monosomy
X (absence of an entire sex chromosome, the Barr body
) is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent (unaffected humans have 46 chromosomes, of which two are sex chromosomes). Normal females have two X chromosomes, but in Turner syndrome, one of those sex chromosomes is missing or has other abnormalities. In some cases, the chromosome is missing in some cells but not others, a condition referred to as mosaicism
or 'Turner mosaicism'.
Occurring in 1 in 2000 – 1 in 5000 phenotypic females, the syndrome manifests itself in a number of ways. There are characteristic physical abnormalities, such as short stature
, swelling, broad chest, low hairline, low-set ears
, and webbed neck
s. Girls with Turner syndrome typically experience gonadal dysfunction (non-working ovaries), which results in amenorrhea (absence of menstrual cycle) and sterility
. Concurrent health concerns are also frequently present, including congenital heart disease
, hypothyroidism
(reduced hormone
secretion by the thyroid
), diabetes
, vision
problems, hearing
concerns, and many autoimmune diseases. Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and memory
areas.
Turner's syndrome is named after Henry H. Turner
.
Other symptoms may include a small lower jaw (micrognathia
), cubitus valgus
(turned-in elbows), soft upturned nails, palmar crease, and drooping eyelids
. Less common are pigmented mole
s, hearing loss, and a high-arch palate (narrow maxilla). Turner syndrome manifests itself differently in each female affected by the condition, and no two individuals will share the same symptoms.
(45XO) and partial monosomy (46XX). 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. In 75% of cases inactivated X chromosome is paternal origin.
There is currently no known cause for Turner syndrome, though there are several theories surrounding the subject. The only solid fact that is known today is that during conception part or all of the second sex chromosome is not transferred to the fetus. In other words, these females do not have Barr bodies
, which are those X chromosomes inactivated by the cell.
during pregnancy. Sometimes, fetuses with Turner syndrome are identified by abnormal ultrasound
findings (i.e. heart defect, kidney abnormality, cystic hygroma
, ascites
). Although the recurrence risk is not increased, genetic counseling
is often recommended for families who have had a pregnancy or child with Turner syndrome.
A test, called a karyotype
or a chromosome analysis, analyzes the chromosomal composition of the individual. This is the test of choice to diagnose Turner syndrome.
s—mostly postductal coarctation of the aorta. When patients with congenital heart disease were omitted from the sample of the study, the mortality from circulatory disorders was not significantly increased.
Cardiovascular malformations are a serious concern as it is the most common cause of death in adults with Turner syndrome. It takes an important part in the 3-fold increase in overall mortality and the reduced life expectancy (up to 13 years) associated with Turner syndrome.
-karyotype
correlations in regard to cardiovascular malformations in Turner syndrome because the number of individuals studied within the less common karyotype groups is too small. Other studies also suggest the presence of hidden mosaicisms that are not diagnosed on usual karyotypic analyses in some patients with 45,X karyotype.
In conclusion, the associations between karyotype and phenotypic characteristics, including cardiovascular malformations, remain questionable.
The variations found in the different studies are mainly attributable to variations in non-invasive methods used for screening and the types of lesions that they can characterize (Ho et al., 2004). However Sybert, 1998 suggests that it could be simply attributable to the small number of subjects in most studies.
Different karyotypes may have differing prevalence of cardiovascular malformations. Two studies found a prevalence of cardiovascular malformations of 30% and 38% in a group of pure 45,X monosomy. But considering other karyotype groups, they reported a prevalence of 24.3% and 11% in patients with mosaic X monosomy, and a prevalence of 11% in patients with X chromosomal structural abnormalities.
The higher prevalence in the group of pure 45,X monosomy is primarily due to a significant difference in the prevalence of aortic valve
abnormalities and coarctation of the aorta, the two most common cardiovascular malformations.
and coarctation (narrowing) of the aorta. Sybert, 1998 found that more than 50% of the cardiovascular malformations observed in her study of individuals with Turner syndrome were bicuspid aortic valves or coarctation of the aorta, alone or in combination.
Other congenital cardiovascular malformations, such as partial anomalous venous drainage and aortic valve stenosis
or aortic regurgitation, are also more common in Turner syndrome than in the general population. Hypoplastic left heart syndrome
represents the most severe reduction in left-sided structures
Up to 15% of adults with Turner syndrome have bicuspid aortic valves, meaning that there are only two, instead of three, parts to the valves in the main blood vessel
leading from the heart
. Since bicuspid valves are capable of regulating blood flow properly, this condition may go undetected without regular screening. However, bicuspid valves are more likely to deteriorate and later fail. Calcification
also occurs in the valves, which may lead to a progressive valvular dysfunction as evidenced by aortic stenosis or regurgitation.
With a prevalence from 12.5% to 17.5% (Dawson-Falk et al., 1992), bicuspid aortic valve is the most common congenital malformation affecting the heart in this syndrome. It is usually isolated but it may be seen in combination with other anomalies, particularly coarctation of the aorta.
Between 5% and 10% of those born with Turner syndrome have coarctation of the aorta, a congenital narrowing of the descending aorta, usually just distal to the origin of the left subclavian artery (the artery that branches off the arch of the aorta to the left arm) and opposite to the duct (and so termed "juxtaductal"). Estimates of the prevalence of this malformation in patients with Turner syndrome ranges from 6.9% to 12.5% (Dawson-Falk et al., 1992). A coarctation of the aorta in a female is suggestive of Turner syndrome, and suggests the need for further tests, such as a karyotype.
This abnormality is a relatively rare congenital heart disease in the general population. The prevalence of this abnormality also is low (around 2.9%) in Turner syndrome. However, its relative risk is 320 in comparison with the general population. Strangely, Turner syndrome seems to be associated with unusual forms of partial anomalous venous drainage.
In the management of a patient with Turner syndrome it is essential to keep in mind that these left-sided cardiovascular malformations in Turner syndrome result in an increased susceptibility to bacterial endocarditis. Therefore prophylactic antibiotics should be considered when procedures with high risk endocarditis are performed, such as dental cleaning.
Turner syndrome is often associated with persistent hypertension
, sometimes in childhood. In the majority of Turner syndrome patients with hypertension, there is no specific cause. In the remainder, it is usually associated with cardiovascular or kidney abnormalities, including coarctation of the aorta.
Sybert, 1998 points out that it remains unproven that aortic root diameters that are relatively large for body surface area but still well within normal limits imply a risk for progressive dilatation.
The prevalence of aortic root dilatation ranges from 8.8% to 42% in patients with Turner syndrome. Even if not every aortic root dilatation necessarily goes on to an aortic dissection
(circumferential or transverse tear of the intima), complications such as dissection, aortic rupture resulting in death may occur. The natural history of aortic root dilatation is still unknown, but it is a fact that it is linked to aortic dissection and rupture, which has a high mortality rate.
Aortic dissection affects 1% to 2% of patients with Turner syndrome. As a result any aortic root dilatation should be seriously taken into account as it could become a fatal aortic dissection. Routine surveillance is highly recommended.
It is well established that cardiovascular malformations (typically bicuspid aortic valve, coarctation of the aorta and some other left-sided cardiac malformations) and hypertension predispose to aortic dilatation and dissection in the general population. At the same time it has been shown that these risk factors are common in Turner syndrome. Indeed these same risk factors are found in more than 90% of patients with Turner syndrome who develop aortic dilatation. Only a small number of patients (around 10%) have no apparent predisposing risk factors. It is important to note that the risk of hypertension is increased 3-fold in patients with Turner syndrome. Because of its relation to aortic dissection blood pressure needs to be regularly monitored and hypertension should be treated aggressively with an aim to keep blood pressure below 140/80 mmHg. It has to be noted that as with the other cardiovascular malformations, complications of aortic dilatation is commonly associated with 45,X karyotype.
The exact role that all these risk factors play in the process leading to such fatal complications is still quite unclear. Aortic root dilatation is thought to be due to a mesenchymal defect as pathological evidence of cystic medial necrosis has been found by several studies. The association between a similar defect and aortic dilatation is well established in such conditions such as Marfan syndrome
. Also, abnormalities in other mesenchymal
tissues (bone matrix and lymphatic vessels) suggests a similar primary mesenchymal defect in patients with Turner syndrome. However there is no evidence to suggest that patients with Turner syndrome have a significantly higher risk of aortic dilatation and dissection in absence of predisposing factors. So the risk of aortic dissection in Turner syndrome appears to be a consequence of structural cardiovascular malformations and hemodynamic risk factors rather than a reflection of an inherent abnormality in connective tissue (Sybert, 1998). The natural history of aortic root dilatation is unknown, but because of its lethal potential, this aortic abnormality needs to be carefully followed.
Turner syndrome is characterized by primary amenorrhea, premature ovarian failure, streak gonads and infertility. However, technology (especially oocyte donation) provides the opportunity of pregnancy in these patients.
As more women with Turner syndrome complete pregnancy thanks to modern techniques to treat infertility, it has to be noted that pregnancy may be a risk of cardiovascular complications for the mother. Indeed several studies had suggested an increased risk for aortic dissection in pregnancy. Three deaths have even been reported. The influence of estrogen
has been examined but remains unclear. It seems that the high risk of aortic dissection during pregnancy in women with Turner syndrome may be due to the increased hemodynamic load rather than the high estrogen rate. Of course these findings are important and need to be remembered while following a pregnant patient with Turner syndrome.
Cardiovascular malformations in Turner syndrome are also very serious, not only because of their high prevalence in that particular population but mainly because of their high lethal potential and their great implication in the increased mortality found in patients with Turner syndrome. Congenital heart disease needs to be explored in every female newly diagnosed with Turner syndrome. As adults are concerned close surveillance of blood pressure is needed to avoid a high risk of fatal complications due to aortic dissection and rupture.
The fourth metacarpal bone (fourth toe and ring finger) may be unusually short, as may the fifth.
Due to inadequate production of estrogen
, many of those with Turner syndrome develop osteoporosis
. This can decrease height further, as well as exacerbate the curvature of the spine, possibly leading to scoliosis
. It is also associated with an increased risk of bone fracture
s.
Some of these conditions can be corrected surgically. Even with these abnormalities, the kidneys of most women with Turner syndrome function normally. However, as noted above, kidney problems may be associated with hypertension
.
, specifically Hashimoto's thyroiditis
. If detected, it can be easily treated with thyroid hormone supplements.
by adult years. The risk of developing type 2 diabetes can be substantially reduced by maintaining a normal weight.
. This may also manifest itself as a difficulty with motor control or with mathematics
. While it is non-correctable, in most cases it does not cause difficulty in daily living. Most Turner Syndrome patients are employed as adults and lead productive lives.
There is also a rare variety of Turner Syndrome, known as "Ring-X Turner Syndrome", which has an approximate 60 percent association with mental retardation. This variety accounts for approximately 2–4% of all Turner Syndrome cases.
. While some women with Turner syndrome have successfully become pregnant and carried their pregnancies to term, this is very rare and is generally limited to those women whose karyotypes are not 45,XO. Even when such pregnancies do occur, there is a higher than average risk of miscarriage
or birth defects, including Turner Syndrome or Down Syndrome. Some women with Turner syndrome who are unable to conceive without medical intervention may be able to use IVF or other fertility treatments.
Usually estrogen replacement therapy is used to spur 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 oocytes).
Turner syndrome is a cause of primary amenorrhea, premature ovarian failure (hypergonadotropic hypogonadism), streak gonads and infertility. Failure to develop secondary sex characteristics (sexual infantilism) is typical.
Especially in mosaic cases of Turner syndrome that contains Y-chromosome (e.g. 45,X0/46,XY) due to the risk of development of ovarian malignancy (most common is gonadoblastoma) gonadectomy is recommended.
, an endocrinologist
from Illinois, who described it in 1938. In Europe, it is often called Ullrich-Turner syndrome or even Bonnevie-Ullrich-Turner syndrome to acknowledge that earlier cases had also been described by European doctors.
The first published report of a female with a 45,X karyotype
was in 1959 by Dr. Charles Ford and colleagues in Harwell, Oxfordshire
and Guy's Hospital
in London
. It was found in a 14-year-old girl with signs of Turner syndrome.
Female
Female is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...
s, of which monosomy
Monosomy
Monosomy is a form of aneuploidy with the presence of only one chromosome from a pair. Partial monosomy occurs when only a portion of the chromosome has one copy, while the rest has two copies.-Human monosomy:...
X (absence of an entire sex chromosome, the Barr body
Barr body
A Barr body is the inactive X chromosome in a female somatic cell, rendered inactive in a process called lyonization, in those species in which sex is determined by the presence of the Y or W chromosome rather than the diploidy of the X or Z...
) is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent (unaffected humans have 46 chromosomes, of which two are sex chromosomes). Normal females have two X chromosomes, but in Turner syndrome, one of those sex chromosomes is missing or has other abnormalities. In some cases, the chromosome is missing in some cells but not others, a condition referred to as mosaicism
Mosaic (genetics)
In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...
or 'Turner mosaicism'.
Occurring in 1 in 2000 – 1 in 5000 phenotypic females, the syndrome manifests itself in a number of ways. There are characteristic physical abnormalities, such as short stature
Short stature
Short stature refers to a height of a human being which is below expected. Shortness is a vague term without a precise definition and with significant relativity to context...
, swelling, broad chest, low hairline, low-set ears
Low-set ears
Low-set ears is a term used to describe a depressed positioning of the pinna two or more standard deviations below the population average.It can be associated with conditions such as:* Down's syndrome and Turner Syndrome* Noonan syndrome* Patau syndrome...
, and webbed neck
Webbed neck
A webbed neck, or pterygium colli deformity, is a congenital skin fold that runs along the sides of the neck down to the shoulders.There are many variants.-Associated conditions:...
s. Girls with Turner syndrome typically experience gonadal dysfunction (non-working ovaries), which results in amenorrhea (absence of menstrual cycle) and sterility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
. Concurrent health concerns are also frequently present, including congenital heart disease
Congenital heart defect
A congenital heart defect is a defect in the structure of the heart and great vessels which is present at birth. Many types of heart defects exist, most of which either obstruct blood flow in the heart or vessels near it, or cause blood to flow through the heart in an abnormal pattern. Other...
, hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
(reduced hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
secretion by the thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
), diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, vision
Ophthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...
problems, hearing
Otology
Otology is a branch of biomedicine which studies normal and pathological anatomy and physiology of the ear as well as its diseases, diagnosis and treatment....
concerns, and many autoimmune diseases. Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
areas.
Turner's syndrome is named after Henry H. Turner
Henry Turner (endocrinologist)
Henry H. Turner was an American endocrinologist, noted for his published description of Turner Syndrome in 1938 at the Association for the Study of Internal Secretions. He served as chief of endocrinology and as associate dean of the University of Oklahoma College of Medicine.Turner was born in...
.
Signs and symptoms
Common symptoms of Turner syndrome include:Other symptoms may include a small lower jaw (micrognathia
Micrognathism
Micrognathism is a condition where the jaw is undersized. It is also sometimes called "Mandibular hypoplasia". It is common in infants, but is usually self-corrected during growth, due to the jaws increasing in size. It may be a cause of abnormal tooth alignment and in severe cases can hamper...
), cubitus valgus
Cubitus valgus
Cubitus valgus is a medical deformity in which the elbows are turned in. A small degree of cubitus valgus is acceptable and occurs in the general population....
(turned-in elbows), soft upturned nails, palmar crease, and drooping eyelids
Ptosis (eyelid)
Ptosis is a drooping of the upper or lower eyelid. The drooping may be worse after being awake longer, when the individual's muscles are tired. This condition is sometimes called "lazy eye", but that term normally refers to amblyopia...
. Less common are pigmented mole
Melanocytic nevus
A melanocytic nevus is a type of lesion that contains nevus cells .Some sources equate the term mole with "melanocytic nevus". Other sources reserve the term "mole" for other purposes....
s, hearing loss, and a high-arch palate (narrow maxilla). Turner syndrome manifests itself differently in each female affected by the condition, and no two individuals will share the same symptoms.
Cause
Risk factors for Turner syndrome are not well known. Genetic mosaicism (46XX/45XO) is most often implicated, alongside nondisjunctionNondisjunction
Nondisjunction is the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2. This could arise from a failure of homologous chromosomes to separate in meiosis I, or the failure of sister chromatids to separate during meiosis II or mitosis. The result of this error is a...
(45XO) and partial monosomy (46XX). Nondisjunctions increase with maternal age, such as for Down syndrome
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...
, 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. In 75% of cases inactivated X chromosome is paternal origin.
There is currently no known cause for Turner syndrome, though there are several theories surrounding the subject. The only solid fact that is known today is that during conception part or all of the second sex chromosome is not transferred to the fetus. In other words, these females do not have Barr bodies
Barr body
A Barr body is the inactive X chromosome in a female somatic cell, rendered inactive in a process called lyonization, in those species in which sex is determined by the presence of the Y or W chromosome rather than the diploidy of the X or Z...
, which are those X chromosomes inactivated by the cell.
Diagnosis
Turner syndrome may be diagnosed by amniocentesisAmniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...
during pregnancy. Sometimes, fetuses with Turner syndrome are identified by abnormal ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
findings (i.e. heart defect, kidney abnormality, cystic hygroma
Cystic hygroma
A cystic hygroma is a congenital multiloculated lymphatic lesion that can arise anywhere, but is classically found in the left posterior triangle of the neck. This is the most common form of lymphangioma. It contains large cyst like cavities containing watery fluid.Microscopically cystic hygroma...
, ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
). Although the recurrence risk is not increased, genetic counseling
Genetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
is often recommended for families who have had a pregnancy or child with Turner syndrome.
A test, called a karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
or a chromosome analysis, analyzes the chromosomal composition of the individual. This is the test of choice to diagnose Turner syndrome.
Prognosis
While most of the physical findings are harmless, there can be significant medical problems associated with the syndrome.Cardiovascular
Price et al. (1986 study of 156 female patients with Turner syndrome) showed a significantly greater number of deaths from diseases of the circulatory system than expected, half of them due to congenital heart defectCongenital heart defect
A congenital heart defect is a defect in the structure of the heart and great vessels which is present at birth. Many types of heart defects exist, most of which either obstruct blood flow in the heart or vessels near it, or cause blood to flow through the heart in an abnormal pattern. Other...
s—mostly postductal coarctation of the aorta. When patients with congenital heart disease were omitted from the sample of the study, the mortality from circulatory disorders was not significantly increased.
Cardiovascular malformations are a serious concern as it is the most common cause of death in adults with Turner syndrome. It takes an important part in the 3-fold increase in overall mortality and the reduced life expectancy (up to 13 years) associated with Turner syndrome.
Cause
According to Sybert, 1998 the data are inadequate to allow conclusions about phenotypePhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
-karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
correlations in regard to cardiovascular malformations in Turner syndrome because the number of individuals studied within the less common karyotype groups is too small. Other studies also suggest the presence of hidden mosaicisms that are not diagnosed on usual karyotypic analyses in some patients with 45,X karyotype.
In conclusion, the associations between karyotype and phenotypic characteristics, including cardiovascular malformations, remain questionable.
Prevalence of cardiovascular malformations
The prevalence of cardiovascular malformations among patients with Turner syndrome ranges from 17% (Landin-Wilhelmsen et al., 2001) to 45% (Dawson-Falk et al., 1992).The variations found in the different studies are mainly attributable to variations in non-invasive methods used for screening and the types of lesions that they can characterize (Ho et al., 2004). However Sybert, 1998 suggests that it could be simply attributable to the small number of subjects in most studies.
Different karyotypes may have differing prevalence of cardiovascular malformations. Two studies found a prevalence of cardiovascular malformations of 30% and 38% in a group of pure 45,X monosomy. But considering other karyotype groups, they reported a prevalence of 24.3% and 11% in patients with mosaic X monosomy, and a prevalence of 11% in patients with X chromosomal structural abnormalities.
The higher prevalence in the group of pure 45,X monosomy is primarily due to a significant difference in the prevalence of aortic valve
Aortic valve
The aortic valve is one of the valves of the heart. It is normally tricuspid , although in 1% of the population it is found to be congenitally bicuspid . It lies between the left ventricle and the aorta....
abnormalities and coarctation of the aorta, the two most common cardiovascular malformations.
Congenital heart disease
The most commonly observed are congenital obstructive lesions of the left side of the heart, leading to reduced flow on this side of the heart. This includes bicuspid aortic valveBicuspid aortic valve
A bicuspid aortic valve is most commonly a congenital condition of the aortic valve where two of the aortic valvular leaflets fuse during development resulting in a valve that is bicuspid instead of the normal tricuspid configuration. Normally the only cardiac valve that is bicuspid is the mitral...
and coarctation (narrowing) of the aorta. Sybert, 1998 found that more than 50% of the cardiovascular malformations observed in her study of individuals with Turner syndrome were bicuspid aortic valves or coarctation of the aorta, alone or in combination.
Other congenital cardiovascular malformations, such as partial anomalous venous drainage and aortic valve stenosis
Aortic valve stenosis
Aortic valve stenosis is a disease of the heart valves in which the opening of the aortic valve is narrowed. The aortic valve is the valve between the left ventricle of the heart and the aorta, which is the largest artery in the body and carries the entire output of blood.-Pathophysiology:The...
or aortic regurgitation, are also more common in Turner syndrome than in the general population. Hypoplastic left heart syndrome
Hypoplastic left heart syndrome
Hypoplastic left heart syndrome , is a rare congenital heart defect in which the left ventricle of the heart is severely underdeveloped.-Causes:...
represents the most severe reduction in left-sided structures
Bicuspid aortic valve
Up to 15% of adults with Turner syndrome have bicuspid aortic valves, meaning that there are only two, instead of three, parts to the valves in the main blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
leading from the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
. Since bicuspid valves are capable of regulating blood flow properly, this condition may go undetected without regular screening. However, bicuspid valves are more likely to deteriorate and later fail. Calcification
Calcification
Calcification is the process in which calcium salts build up in soft tissue, causing it to harden. Calcifications may be classified on whether there is mineral balance or not, and the location of the calcification.-Causes:...
also occurs in the valves, which may lead to a progressive valvular dysfunction as evidenced by aortic stenosis or regurgitation.
With a prevalence from 12.5% to 17.5% (Dawson-Falk et al., 1992), bicuspid aortic valve is the most common congenital malformation affecting the heart in this syndrome. It is usually isolated but it may be seen in combination with other anomalies, particularly coarctation of the aorta.
Coarctation of the aorta
Between 5% and 10% of those born with Turner syndrome have coarctation of the aorta, a congenital narrowing of the descending aorta, usually just distal to the origin of the left subclavian artery (the artery that branches off the arch of the aorta to the left arm) and opposite to the duct (and so termed "juxtaductal"). Estimates of the prevalence of this malformation in patients with Turner syndrome ranges from 6.9% to 12.5% (Dawson-Falk et al., 1992). A coarctation of the aorta in a female is suggestive of Turner syndrome, and suggests the need for further tests, such as a karyotype.
Partial anomalous venous drainage
This abnormality is a relatively rare congenital heart disease in the general population. The prevalence of this abnormality also is low (around 2.9%) in Turner syndrome. However, its relative risk is 320 in comparison with the general population. Strangely, Turner syndrome seems to be associated with unusual forms of partial anomalous venous drainage.
In the management of a patient with Turner syndrome it is essential to keep in mind that these left-sided cardiovascular malformations in Turner syndrome result in an increased susceptibility to bacterial endocarditis. Therefore prophylactic antibiotics should be considered when procedures with high risk endocarditis are performed, such as dental cleaning.
Turner syndrome is often associated with persistent hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, sometimes in childhood. In the majority of Turner syndrome patients with hypertension, there is no specific cause. In the remainder, it is usually associated with cardiovascular or kidney abnormalities, including coarctation of the aorta.
Aortic dilation, dissection, and rupture
Two studies have suggested aortic dilatation in Turner syndrome, typically involving the root of the ascending aorta and occasionally extending through the aortic arch to the descending aorta, or at the site of previous coarctation of the aorta repair.- Allen et al., 1986 who evaluated 28 girls with Turner syndrome, found a significantly greater mean aortic root diameter in patients with Turner syndrome than in the control group (matched for body surface area). Nonetheless, the aortic root diameter found in Turner syndrome patients were still well within the limits.
- This has been confirmed by the study of Dawson-Falk et al., 1992 who evaluated 40 patients with Turner syndrome. They presented basically the same findings: a greater mean aortic root diameter, which nevertheless remains within the normal range for body surface area.
Sybert, 1998 points out that it remains unproven that aortic root diameters that are relatively large for body surface area but still well within normal limits imply a risk for progressive dilatation.
Prevalence of aortic abnormalities
The prevalence of aortic root dilatation ranges from 8.8% to 42% in patients with Turner syndrome. Even if not every aortic root dilatation necessarily goes on to an aortic dissection
Aortic dissection
Aortic dissection occurs when a tear in the inner wall of the aorta causes blood to flow between the layers of the wall of the aorta and force the layers apart. The dissection typically extends anterograde, but can extend retrograde from the site of the intimal tear. Aortic dissection is a medical...
(circumferential or transverse tear of the intima), complications such as dissection, aortic rupture resulting in death may occur. The natural history of aortic root dilatation is still unknown, but it is a fact that it is linked to aortic dissection and rupture, which has a high mortality rate.
Aortic dissection affects 1% to 2% of patients with Turner syndrome. As a result any aortic root dilatation should be seriously taken into account as it could become a fatal aortic dissection. Routine surveillance is highly recommended.
Risk factors for aortic rupture
It is well established that cardiovascular malformations (typically bicuspid aortic valve, coarctation of the aorta and some other left-sided cardiac malformations) and hypertension predispose to aortic dilatation and dissection in the general population. At the same time it has been shown that these risk factors are common in Turner syndrome. Indeed these same risk factors are found in more than 90% of patients with Turner syndrome who develop aortic dilatation. Only a small number of patients (around 10%) have no apparent predisposing risk factors. It is important to note that the risk of hypertension is increased 3-fold in patients with Turner syndrome. Because of its relation to aortic dissection blood pressure needs to be regularly monitored and hypertension should be treated aggressively with an aim to keep blood pressure below 140/80 mmHg. It has to be noted that as with the other cardiovascular malformations, complications of aortic dilatation is commonly associated with 45,X karyotype.
Pathogenesis of aortic dissection and rupture
The exact role that all these risk factors play in the process leading to such fatal complications is still quite unclear. Aortic root dilatation is thought to be due to a mesenchymal defect as pathological evidence of cystic medial necrosis has been found by several studies. The association between a similar defect and aortic dilatation is well established in such conditions such as Marfan syndrome
Marfan syndrome
Marfan syndrome is a genetic disorder of the connective tissue. People with Marfan's tend to be unusually tall, with long limbs and long, thin fingers....
. Also, abnormalities in other mesenchymal
Mesenchymal stem cell
Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types, including: osteoblasts , chondrocytes and adipocytes...
tissues (bone matrix and lymphatic vessels) suggests a similar primary mesenchymal defect in patients with Turner syndrome. However there is no evidence to suggest that patients with Turner syndrome have a significantly higher risk of aortic dilatation and dissection in absence of predisposing factors. So the risk of aortic dissection in Turner syndrome appears to be a consequence of structural cardiovascular malformations and hemodynamic risk factors rather than a reflection of an inherent abnormality in connective tissue (Sybert, 1998). The natural history of aortic root dilatation is unknown, but because of its lethal potential, this aortic abnormality needs to be carefully followed.
Pregnancy
Turner syndrome is characterized by primary amenorrhea, premature ovarian failure, streak gonads and infertility. However, technology (especially oocyte donation) provides the opportunity of pregnancy in these patients.
As more women with Turner syndrome complete pregnancy thanks to modern techniques to treat infertility, it has to be noted that pregnancy may be a risk of cardiovascular complications for the mother. Indeed several studies had suggested an increased risk for aortic dissection in pregnancy. Three deaths have even been reported. The influence of estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
has been examined but remains unclear. It seems that the high risk of aortic dissection during pregnancy in women with Turner syndrome may be due to the increased hemodynamic load rather than the high estrogen rate. Of course these findings are important and need to be remembered while following a pregnant patient with Turner syndrome.
Cardiovascular malformations in Turner syndrome are also very serious, not only because of their high prevalence in that particular population but mainly because of their high lethal potential and their great implication in the increased mortality found in patients with Turner syndrome. Congenital heart disease needs to be explored in every female newly diagnosed with Turner syndrome. As adults are concerned close surveillance of blood pressure is needed to avoid a high risk of fatal complications due to aortic dissection and rupture.
Skeletal
Normal skeletal development is inhibited due to a large variety of factors, mostly hormonal. The average height of a woman with Turner syndrome, in the absence of growth hormone treatment, is (140 cm). Patients with Turner's mosaicism can reach normal average height.The fourth metacarpal bone (fourth toe and ring finger) may be unusually short, as may the fifth.
Due to inadequate production of estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
, many of those with Turner syndrome develop osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
. This can decrease height further, as well as exacerbate the curvature of the spine, possibly leading to scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
. It is also associated with an increased risk of bone fracture
Bone fracture
A bone fracture is a medical condition in which there is a break in the continuity of the bone...
s.
Kidney
Approximately one-third of all women with Turner syndrome have one of three kidney abnormalities:- A single, horseshoe-shaped kidney on one side of the body.
- An abnormal urine-collecting system.
- Poor blood flow to the kidneys.
Some of these conditions can be corrected surgically. Even with these abnormalities, the kidneys of most women with Turner syndrome function normally. However, as noted above, kidney problems may be associated with hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Thyroid
Approximately one-third of all women with Turner syndrome have a thyroid disorder. Usually it is hypothyroidismHypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, specifically Hashimoto's thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
. If detected, it can be easily treated with thyroid hormone supplements.
Diabetes
Women with Turner syndrome are at a moderately increased risk of developing type 1 diabetes in childhood and a substantially increased risk of developing type 2 diabetesDiabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
by adult years. The risk of developing type 2 diabetes can be substantially reduced by maintaining a normal weight.
Cognitive
Turner syndrome does not typically cause mental retardation 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 disorderNonverbal learning disorder
A nonverbal learning disorder or nonverbal learning disability is a condition characterized by a significant discrepancy between higher verbal and lower motor, visuo-spatial, and social skills on an IQ test...
. This may also manifest itself as a difficulty with motor control or with mathematics
Mathematics
Mathematics is the study of quantity, space, structure, and change. Mathematicians seek out patterns and formulate new conjectures. Mathematicians resolve the truth or falsity of conjectures by mathematical proofs, which are arguments sufficient to convince other mathematicians of their validity...
. While it is non-correctable, in most cases it does not cause difficulty in daily living. Most Turner Syndrome patients are employed as adults and lead productive lives.
There is also a rare variety of Turner Syndrome, known as "Ring-X Turner Syndrome", which has an approximate 60 percent association with mental retardation. This variety accounts for approximately 2–4% of all Turner Syndrome cases.
Reproductive
Women with Turner syndrome are almost universally infertileInfertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
. While some women with Turner syndrome have successfully become pregnant and carried their pregnancies to term, this is very rare and is generally limited to those women whose karyotypes are not 45,XO. Even when such pregnancies do occur, there is a higher than average risk of miscarriage
Miscarriage
Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...
or birth defects, including Turner Syndrome or Down Syndrome. Some women with Turner syndrome who are unable to conceive without medical intervention may be able to use IVF or other fertility treatments.
Usually estrogen replacement therapy is used to spur 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 oocytes).
Turner syndrome is a cause of primary amenorrhea, premature ovarian failure (hypergonadotropic hypogonadism), streak gonads and infertility. Failure to develop secondary sex characteristics (sexual infantilism) is typical.
Especially in mosaic cases of Turner syndrome that contains Y-chromosome (e.g. 45,X0/46,XY) due to the risk of development of ovarian malignancy (most common is gonadoblastoma) gonadectomy is recommended.
Treatment
As a chromosomal condition, there is no cure for Turner syndrome. However, much can be done to minimize the symptoms. For example:- Growth hormoneGrowth hormoneGrowth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
, either alone or with a low dose of androgenAndrogenAndrogen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
, will increase growth and probably final adult height. Growth hormone is approved by the U.S. Food and Drug AdministrationFood and Drug AdministrationThe Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
for treatment of Turner syndrome and is covered by many insurance plans. There is evidence that this is effective, even in toddlers.
- Estrogen replacement therapyHormone therapyHormone therapy, or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also referred to as hormonal therapy...
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 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.
- Modern reproductive technologiesReproductive technologyReproductive technology encompasses all current and anticipated uses of technology in human and animal reproduction, including assisted reproductive technology, contraception and others.-Assisted reproductive technology:...
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
Approximately 99 percent of all fetuses with Turner syndrome result in spontaneous termination during the first trimester. Turner syndrome accounts for about 10 percent of the total number of spontaneous abortions in the United States. The incidence of Turner syndrome in live female births is believed to be around 1 in 2000.History
The syndrome is named after Henry Hubert TurnerHenry Turner (endocrinologist)
Henry H. Turner was an American endocrinologist, noted for his published description of Turner Syndrome in 1938 at the Association for the Study of Internal Secretions. He served as chief of endocrinology and as associate dean of the University of Oklahoma College of Medicine.Turner was born in...
, an endocrinologist
Endocrinology
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
from Illinois, who described it in 1938. In Europe, it is often called Ullrich-Turner syndrome or even Bonnevie-Ullrich-Turner syndrome to acknowledge that earlier cases had also been described by European doctors.
The first published report of a female with a 45,X karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
was in 1959 by Dr. Charles Ford and colleagues in Harwell, Oxfordshire
Harwell, Oxfordshire
Harwell is a village and civil parish in the Vale of White Horse west of Didcot. It was part of Berkshire until the 1974 boundary changes transferred it to Oxfordshire.-Amenities:...
and Guy's Hospital
Guy's Hospital
Guy's Hospital is a large NHS hospital in the borough of Southwark in south east London, England. It is administratively a part of Guy's and St Thomas' NHS Foundation Trust. It is a large teaching hospital and is home to the King's College London School of Medicine...
in London
London
London is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...
. It was found in a 14-year-old girl with signs of Turner syndrome.
See also
- Gonadal dysgenesisGonadal dysgenesisGonadal dysgenesis is a term used to describe multiple reproductive system development disorders. They are conditions of genetic origin. It is characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo....
, for related abnormalities, - Other human sex chromosome aneuploidsAneuploidyAneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders . Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes do not separate...
:- XYY syndromeXYY syndromeXYY syndrome is an aneuploidy of the sex chromosomes in which a human male receives an extra Y-chromosome, giving a total of 47 chromosomes instead of the more usual 46. This produces a 47,XYY karyotype...
, - Klinefelter's syndromeKlinefelter's syndromeKlinefelter syndrome, 46/47, XXY, or XXY syndrome is a condition in which human males have an extra X chromosome. While females have an XX chromosomal makeup, and males an XY, affected individuals have at least two X chromosomes and at least one Y chromosome...
(XXY), - Triple X syndromeTriple X syndromeTriple X syndrome is a form of chromosomal variation characterized by the presence of an extra X chromosome in each cell of a human female. The condition always produces females, with an XX pair of chromosomes, as well as an additional chromosome, resulting in the formation of XXX. A mosaic form...
,
- XYY syndrome
- DermatoglyphicsDermatoglyphicsDermatoglyphics is the scientific study of fingerprints. The term was coined by Dr. Harold Cummins, the father of American fingerprint analysis, even though the process of fingerprint identification had already been in use for several hundred years. All primates have ridged skin...
, - Noonan syndromeNoonan syndromeNoonan Syndrome is a relatively common autosomal dominant congenital disorder considered to be a type of dwarfism, that affects both males and females equally. It used to be referred to as the male version of Turner's syndrome ; however, the genetic causes of Noonan syndrome and Turner syndrome...
, a disorder which is often confused with Turner syndrome because of several physical features that they have in common.
External links
- Turner Syndrome Society of the United States
- Turner Syndrome at the National Institute of Child Health and Human Development
- YourChild: Turner Syndrome: University of Michigan Health System
- Endocrine and Metabolic Diseases Information Service
- The Turner Syndrome Support Society is a national charity caring for the needs of those with Turner Syndrome throughout the United Kingdom.
- Turner Contact Group Ireland - TCGI - is a charity supporting those affected by Turner Syndrome in Ireland.
- New Zealand Turner Syndrome Support Group a New Zealand charity supporting people with Turner Syndrome