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Turner syndrome

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Turner syndrome
   Classifications and external resources

     ICD- 10   Q 96.
     ICD- 9    758.6
   DiseasesDB  13461
   MedlinePlus 000379
    eMedicine  ped/2330

   Turner syndrome encompasses several chromosomal abnormalities, of which
   monosomy X, is the most common. It occurs in 1 out of every 2,500
   female births. Instead of the normal XX sex chromosomes for a female,
   only one X chromosome is present and fully functional. This is called
   45,X or 45,X0, although other genetic variants occur. In Turner
   syndrome, female sexual characteristics are present but underdeveloped.

Symptoms

   Common symptoms of Turner syndrome include:
     * Short stature
     * Lymphoedema (swelling) of the hands and feet
     * Broad chest (shield chest) and widely-spaced nipples
     * Low hairline
     * Low-set ears
     * Reproductive sterility
     * Amenorrhea, or the absence of a menstrual period

   Other symptoms may include a small lower jaw (micrognathia), cubitus
   valgus (turned-in elbows), a webbed neck, soft upturned nails, Simian
   crease and drooping eyelids. Less common are pigmented moles, 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.

Genetics

   Turner syndrome is characterized by the presence of a single complete
   functioning sex-determining chromosome, the X chromosome, instead of
   two, either XX or XY. This chromosomal arrangement normally occurs in
   four ways.
     * During meiosis in either parent, a nondisjunction event can occur
       that leaves the gamete, either oocyte or spermatocyte with neither
       X nor Y chromosome. When this gamete combines with a gamete from
       the other parent (with a normal X chromosome), the embryo lacks the
       normal two chromosomes. Normally, humans have 46 chromosomes, so
       this leaves the embryo with 45 chromosomes and a single X
       chromosome, denoted 45,X (or, sometimes 45,XO, where the "O" is
       used as a placeholder). This is found in 50% of individuals with
       Turner syndrome.

     * During development leading up to gametogenesis, an X chromosome
       loses a portion of the smaller arm, with the end of the long arm
       wrapping around — creating a ring-like structure. The chromosome is
       missing the short arm of the X chromosome. When combined with a
       normal X chromosome in an embryo, the individual has just a single
       copy of the information on the short arm of the X chromosome. This
       is denoted as 46, XrXp-, where rXp- means a ring chromosome missing
       the small (p) arm of the chromosome. Other chromosomal variants
       have two long arms of the X chromosomes attached, and are called
       isochromosomes. Variants of chromosomal structure occur in 30% of
       individuals with Turner syndrome.

     * During an early cell division of the zygote, a nondisjunction event
       occurs and creates a cell line that is missing the second X
       chromosome. In this case, individuals most likely have a mixture of
       46,XX cells and 45,X cells. This is called mosaicism. The exact
       mixture of those two cell types depends on when the nondisjunction
       occurred. It is possible for a very early nondisjunction from a
       46,XY zygote to be completely 45,X (and are indistinguishable from
       the first classification). If the nondisjunction occurs later, a
       45,X/46,XY individual will develop as a male, without Turner
       syndrome. Mosaicism is found in about 20% of individuals with
       Turner syndrome.

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

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

   Risk factors for Turner syndrome are not well known. Nondisjunctions
   increase with maternal age, such as for Down syndrome, but that effect
   is not clear for Turner syndrome.

Incidence

   Approximately 98% of all fetuses with Turner syndrome spontaneously
   abort. Fetuses with Turner syndrome make up about 10% of the total
   number of spontaneously aborted fetuses in the United States. The
   incidence of Turner syndrome in live births is believed to be 1 in
   2500.

History

   The syndrome is named after Henry Turner, an Oklahoma endocrinologist,
   who described it in 1938. In Europe, it is often called Ullrich-Turner
   syndrome or even Bonnevie-Ulrich-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.

Diagnosis

   Turner syndrome may be diagnosed by amniocentesis during pregnancy.
   Sometimes, fetuses with Turner syndrome are identified by abnormal
   ultrasound findings (i.e. heart defect, kidney abnormality, cystic
   hygroma, ascities). 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 blood test, called a karyotype, analyzes the chromosomal composition
   of the individual. This is the most commonly used blood test to
   diagnose Turner syndrome.

Prognosis

   While most of the symptoms of Turner syndrome are harmless, some can
   lead to significant medical problems.

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
   disease. 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.

   Often associated with webbing of the neck and coarctation of the aorta.

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% (Mazanti et al, 1998 …594 patients with Turner
   syndrome) and 38% (Gotzsche et al, 1994 …393 patients with Turner
   syndrome) in a group of pure 45X monosomy. But considering other
   karyotype groups, they reported a prevalence of 24.3% (Mazanti et al,
   1998) and 11% (Gotzsche et al, 1994) in patients with mosaic X monosomy
   , and Mazanti et al, 1998 found a prevalence of 11% in patients with X
   chromosomal structural abnormalities.

   The higher prevalence in the group of pure 45X monosomy is primarily
   due to a significant difference in the prevalence of aortic valve
   abnormalities and aortic coarctation, the two most common
   cardiovascular malformations.

   Though according to Sybert, 1998 there is inadequate data to allow
   conclusions for regarding phenotype- karyotype correlations in regard
   to cardiovascular malformations in Turner syndrome because the number
   of individuals with the less common karyotype groups that has been
   studied is too small. Other studies also suggest the presence of hidden
   mosaicisms that are not diagnosed on usual karyotypic analyses in some
   patients with 45X karyotype.

   In conclusion the associations between karyotype and phenotypic
   characteristics, including cardiovascular malformations, remain
   questionable.

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 mainly includes bicuspid aortic valve and coarctation of
   the aorta. Sybert, 1998 found that more than 50% of the cardiovascular
   malformations observed in her study were bicuspid aortic valve or
   coarctation of the aorta alone or in combination.

   Other congenital cardiovascular malformations such partial anomalous
   venous drainage and aortic stenosis or regurgitation are also more
   common in Turner syndrome compared with the general population.
   Hypoplastic left heart syndrome represents the most severe reduction in
   left-sided structures. Though rare in the population at large, this
   feature is quite common in those with Turner syndrome.

   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 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 must work harder than ordinary heart valves
   and are therefore more likely to deteriorate and later fail.

   With a prevalence from 12.5% (Mazanti et al, 1998) to 17.5%
   (Dawson-Falk et al, 1992), Bicuspid aortic valve is the most common
   congenital malformation affecting the heart. Hypotheses have been
   proposed to explain this abnormal aortic valve but the pathogenesis
   remains unknown. It is usually isolated but it may be seen in
   combination with other anomalies, particularly coarctation of the aorta
   (a quite common association). As this malformation calcifies it may
   lead to a progressive valvular dysfunction as evidenced by aortic
   stenosis or regurgitation (Elsheikh et al, 2002).

   Coarctation of the aorta. Between 5% and 10% of those born with Turner
   syndrome have coarctation of the aorta, a condition which if untreated
   causes blood to flow in a thin, fast stream against the side of the
   heart. This can lead to heart rupture (see below). Coarctation of the
   aorta can be corrected surgically as soon as it is detected.

   Coarctation of the aorta consists in a congenital narrowing of the
   descending aorta, usually just distal to the origin of the left
   subclavian artery and opposite to the duct (and so termed
   “juxtaductal”). While it's more common in boys, estimates of the
   prevalence of this malformation in patients with Turner syndrome ranges
   from 6.9% (Mazanti et al, 1998) to 12.5% (Dawson-Falk et al, 1992). A
   coarctation of the aorta in a female might be quite suggestive of
   Turner syndrome. It has to be noted the important relative risk of 160
   found by the Mazanti et al, 1998 study.

   Partial anomalous venous drainage. This abnormality is a relatively
   rare congenital heart disease in the general population. The prevalence
   of this abnormality is low (around 2.9%) in Turner syndrome. However,
   it is interesting to note that with a relative risk of 320 it is the
   highest risk, in comparison with the general population. Strangely,
   Turner syndrome seems to be associated with quite unusual forms of
   partial anomalous venous drainage. (Mazanti et al, 1998 and
   Prandstraller et al, 1999)

   For the management of a patient with Turner syndrome it is essential to
   keep in mind that all these left-sided cardiovascular malformations
   often found in Turner syndrome result in an increased susceptibility to
   infective endocarditis. Therefore prophylactic antibiotics should be
   considered when procedures with high risk of infection need to be
   performed (Elsheikh et al, 2002).

   Turner syndrome is often associated with persistent hypertension,
   sometimes even in childhood. In the majority of Turner syndrome
   patients with hypertension, there is no specific cause. In the
   remainder, it is usually associated with heart or kidney abnormalities.

Aortic dilation, dissection and rupture

   Two studies had 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 (Lin et al, 1998).
     * Firstly 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 that of the control group
       (matched for body surface area). Nonetheless it is important to add
       that 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, that means a greater mean aortic root
       diameter which however remains in the normal range for body surface
       area.

   Sybert, 1998 points out the fact that it however remains unproven that
   aortic root diameters, relatively large for body surface area but still
   well within normal limits, imply a risk for progressive dilatation.

   Prevalence
          The prevalence of aortic root dilatation ranges from 8,8% (Lin
          et al, 1986) to 42% (Elsheikh et al, 2001) in patients with
          Turner syndrome.
          Even if not every aortic root dilatation necessarily goes on to
          dissect, complications such as dissection (circumferential or
          transverse tear of the intima), rupture and possibly death often
          occur. Indeed even if the natural history of aortic root
          dilatation is still unknown, the risk of aortic dissection or
          rupture could be as high as 60% according to some studies.
          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 abnormality.
          Routine surveillance is highly recommended (Elsheikh et al,
          2002).

   Risk factors
          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
          highly present 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 45X karyotype (Elsheikh et al, 2002).

   Pathogenesis
          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 (Lin et al, 1986).
          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).
          As no studies have been able to clearly expose the natural
          history of aortic root dilatation and because of its lethal
          potential, this aortic abnormality needs to be carefully
          followed-up.

   Pregnancy
          As more women with Turner syndrome complete pregnancy thanks to
          the new modern techniques to treat infertility, it has to be
          noted that pregnancy may be at risk for cardiovascular
          complications.
          Indeed several studies had suggested an increased risk for
          aortic dissection in pregnancy (Lin et al, 1998). 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 oestrogen rate (Elsheikh et al, 2002).
          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 closed
   surveillance of blood pressure is highly needed to avoid a higher risk
   of fatal complications in aortic root dilatation.

   A greater knowledge of the natural history and pathogenesis is needed
   in order to propose a better management and prevention of these
   malformations. It would therefore be interesting to examine the
   different causes mentioned by some studies in order to explain why
   patients with Turner syndrome are more susceptible to cardiovascular
   malformations that the general population.

Skeletal

   Normal skeletal development is inhibited due to a large variety of
   factors, mostly hormonal. The head, neck, and chest of women with
   Turner syndrome are usually of normal size, but the arms and legs are
   unusually short. The average height of a woman with Turner syndrome is
   4'7", or about 140cm.

   The fourth metacarpal bone (fourth toe and ring finger) may be
   unusually short.

   Due to inadequate circulation 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
   fractures.

Kidney

   Approximately one-third of all women with Turner syndrome have one of
   three kidney abnormalities:
    1. A single, horseshoe-shaped kidney on one side of the body, and no
       kidney on the other side.
    2. An abnormal urine-collecting system.
    3. 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.

Thyroid

   Approximately one-third of all women with Turner syndrome have a
   thyroid disorder. Usually it is hypothyroidism, specifically
   Hashimoto's thyroiditis. 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 diabetes by adult years.

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 Non-Verbal Learning Disorder. 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.

Reproductive

   Women with Turner syndrome are almost universally infertile. 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 45X0. Even when such
   pregnancies do occur, there is a higher than average risk of
   miscarriage or birth defects. Some women with Turner syndrome who are
   unable to conceive without medical intervention may be able to benefit
   from the use of IVF or other fertility treatments.

   Usually hormone replacement is used to spur growth of secondary sexual
   characteristics at the time when puberty should onset. This generally
   induces menstruation, though the vast majority of women with Turner
   syndrome will still be infertile.

Treatment

   As a chromosomal condition, there is no "cure" for Turner syndrome.
   However much can be done to minimize the symptoms. For example:
     * Growth hormone, either alone or with a low dose of androgen, will
       improve growth and probably final adult height. Growth hormone is
       approved by the Food and Drug Administration for treatment of
       Turner syndrome and is covered by many insurance plans.

     * Estrogen replacement therapy has been used since the condition was
       described in 1938 to promote development of secondary sexual
       characteristics. Estrogens are also important for maintaining good
       tissue and bone integrity.

     * 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.

   Retrieved from " http://en.wikipedia.org/wiki/Turner_syndrome"
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