What is Turner Syndrome?

Turner Syndrome

Turner syndrome or Ullrich-Turner syndrome (also known as "Gonadal dysgenesis") encompasses several conditions, of which monosomy X (absence of an entire sex chromosome) is most common. It is a chromosomal disorder in which all or part of one of the sex chromosomes is absent (unaffected humans have 46 chromosomes, of which 2 are sex chromosomes). Typical females have 2 X chromosomes, but in Turner syndrome, one of those sex chromosomes is missing or has other abnormalities. In some cases, the missing chromosome is present in some cells but not others, a condition referred to as mosaicism or 'Turner mosaicism'.

Occurring in 1 out of every 2500 girls, 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 necks. 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 other autoimmune diseases. Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and memory areas.

Turner Syndrome Symptoms

Common symptoms of Turner syndrome include:

Other symptoms may include a small lower jaw (micrognathia), cubitus valgus (turned-out elbows), soft upturned nails, palmar 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.

Turner Syndrome Risk Factors

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

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

Turner Syndrome Incidence

Approximately 98 percent of all fetuses with Turner syndrome result in miscarriage. 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 1 in 2500.

Turner Syndrome 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-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 and Guy's Hospital in London. It was found in a 14-year-old girl with signs of Turner syndrome.

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, 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.

Turner Syndrome Prognosis

While most of the physical findings in Turner syndrome 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 disease—mostly preductal 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 is inadequate to allow conclusions about phenotype-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.

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% in a group of pure 45,X monosomy. But considering other karyotype groups, they reported a prevalence of 24.3% 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 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%

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.

• 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%

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.

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 45,X. 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.

Turner Syndrome 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 increase growth and probably final adult height. Growth hormone is approved by the U.S. Food and Drug Administration for treatment of Turner syndrome and is covered by many insurance plans. There is evidence that this is effective, even in toddlers.

• Estrogen replacement 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.

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