Turner Syndrome

Ideogram of the human chromosome X.Source: Wikimedia Commons, National Institutes of Health.

Turner syndrome (TS) is a genetic disorder caused by a partially or completely missing X chromosome. The disorder causes short stature, infertility, and characteristic facial, head and neck features and may also cause cardiac, endocrine and kidney abnormalities. Turner syndrome only affects females.

Other Names

• Monosomy X
• Turner's Syndrome
• Ullrich-Turner syndrome
• 45,X
• Mosaic Turner syndrome

Types

About half of individuals with Turner syndrome have monosomy X, which means each cell in the individual's body has only one copy of the X chromosome instead of the usual two copies. In monosomy X, the chromosomal abnormality occurs as a random event during the formation of reproductive cells (eggs and sperm).

An error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have a single X chromosome in each cell and will be missing the other sex chromosome.

Some women with Turner syndrome have a chromosomal change in only some of their cells, which is known as mosaicism. Mosaic Turner syndrome is not inherited, but occurs as a random event during cell division in early fetal development. As a result, some of an affected person's cells have the usual two sex chromosomes (either two X chromosomes or one X chromosome and one Y chromosome), and other cells have only one copy of the X chromosome. Other sex chromosome abnormalities are also possible in females with X chromosome mosaicism.

Signs and Symptoms

Turner syndrome can present with a variety of signs and symptoms. These may include:

Structural abnormalities

• Flat, broad chest shaped like a shield
• Dry eyes
• Drooping eyelids
• Flat feet
• Narrowing of the aorta
• Low set ears
• Webbed neck
• Retrognathia (receding lower jaw)
• Narrow, high-arched palate (roof of the mouth)
• Cubitus valgus (arms that turn out slightly at the elbows)
• Scoliosis (curvature of the spine)

Reportuctive abnormalities

• Absent or incomplete development at puberty, including sparse pubic hair and small breasts
• Normal external vaginal organs
• Uterus and fallopian tubes are present
• Lack of ovaries
• Lack of testes
• Vaginal dryness, can lead to painful intercourse
• Infertility
• Lack of menstruation

Endocrine abnormalities

• Short stature
• Osteoporosis
• Diabetes (increased risk of Type II Diabetes)
• Thyroid (usually hypothyroidism or low thyroid function)

Other problems

• Some individuals with Turner syndrome have structural problems with the heart or major blood vessels. High blood pressure also affects about 20% of girls and 40% of adults with Turner syndrome.
• The kidneys may be structurally abnormal in Turner syndrome, although kidney function is usually normal.
• Although people with Turner syndrome have normal intelligence, some have problems with specific visual-spatial coordination tasks (such as mentally rotating objects in space) and may have trouble learning math (geometry and arithmetic).

Causes

Human beings typically have 46 chromosomes. These chromosomes contain genes and DNA, the blueprints of human development. Two of these chromosomes determine the person's sexual characteristics (the sex chromosomes). Females have two sex chromosomes that are the same. These two are labeled X and are written as XX. Males differ in that they have an X and a Y chromosome, which are written as XY.

In Turner syndrome, affected individuals have an abnormal X chromosome. The X chromosome may be either completely or partially absent. Because the alteration in genetic material occurs during fetal development, the features of Turner syndrome are present from birth.

Researchers have not determined which genes on the X chromosome are responsible for most of the features of Turner syndrome. They have, however, identified one gene called SHOX that is important for bone development and growth. Missing one copy of this gene likely causes the short stature and skeletal abnormalities in women with Turner syndrome.

The X chromosome abnormality may occur as a random event during the formation of reproductive cells (monosomy X) or may be inherited (nondisjunction or mosaicism).

Diagnosis

Turner Syndrome is often suspected because of the characteristic physical features associated with the syndrome (short stature, webbed neck, low hairline, low-set ears, swollen hands and feet), especially if cardiac or kidney problems are noted in addition to the physical characteristics.

Exams and tests

Once Turner syndrome is suspected, chromosomal karyotyping can make the final determination. Additional tests which may help with diagnosis and evaluation of Turner syndrome include MRI of the chest, echocardiogram of the heart, and blood tests which evaluate the levels of lutenizing hormone (LH) and follicle stimulating hormone (FSH). Ultrasound of the reproductive organs and kidneys as well as a pelvic examination may show abnormal development.

Turner's syndrome may also be diagnosed in utero through amniocentesis or chorionic villus sampling. The characteristic features may be seen on prenatal ultrasound, suggesting a diagnosis of Turner syndrome. ^[1]

Treatment

Although there is no cure for Turner syndrome, there are some treatments that can help minimize the symptoms.

• Human growth hormone (hGH) given in early childhood can often increase adult height by a few inches.
• Estrogen replacement therapy (ERT) can help start up secondary sexual development (such as breast development or developing wider hips) that normally begins at puberty for girls without Turner Syndrome. Health care providers may prescribe ERT to girls who haven’t started menstruating by age 15. ERT should also help prevent osteoporosis.

Holistic and alternative treatments

Currently there is no cure or treatment to reverse the genetic condition of Turner Syndrome. However the advent of a healthy diet and natural eating approach will help curtail some of the effects of Turner Syndrome. Both weight gain and diabetes are two negative impacts seen in Turner Syndrome patients. Holistic medicine and a healthy diet can help curtail the tendency to develop osteoporosis, diabetes, related problems seen in Turner syndrome.

Living with Turner Syndrome

Caring for someone with Turner Syndrome

Caring for Turner syndrome patients usually occurs during childhood as most people have no problems with the normal activities of daily living as they age.

Parents of children with Turner syndrome should be aware of the conditions associated with this genetic malformation. Feeding a healthy diet, helping to structure the education of children as they grow, and being aware of other concerns surrounding their development and health will yield greater success and happier, more productive lives for these children.

Chances of developing Turner syndrome

Turner syndrome occurs in about 1 out of 2,000 live births.

Heredity

While Turner syndrome is genetic in that it involves the complete or partial absence of X chromosome genes (see the Causes section), it is not usually hereditary in the conventional sense. That is, it does not typically "run in families."

The one rare exception is in families with an X chromosome deletion, which is stable enough to be passed down through the generations and which also allows fertility.

Related Problems

• Babies born with a heart murmur or narrowing of the aorta may need surgery to correct the problem. A heart expert (cardiologist) will assess and follow up any treatment necessary.
• Girls who have Turner syndrome are more likely to get middle ear infections. Repeated infections may lead to hearing loss and should be evaluated by the pediatrician. An ear, nose and throat specialist (ENT) may be involved in caring for this health issue.
• High blood pressure is quite common in women who have Turner syndrome. In some cases, the elevated blood pressure is due to narrowing of the aorta or a kidney abnormality. However, most of the time, no specific cause for the elevation is identified. Blood pressure should be checked routinely and, if necessary, treated with medication.
• Women who have Turner syndrome have a slightly higher risk of having an under active thyroid or developing diabetes. This should also be monitored during routine health maintenance visits and treated if necessary.
• Infertility is a very common complication of Turner syndrome. Assistive reproductive therapies, such as egg donation, may help some women with Turner Syndrome get pregnant.

Regular health checks are very important. Special clinics for the care of girls and women who have Turner syndrome are available in some areas, with access to a variety of specialists. Early preventive care and treatment is very important. Having appropriate medical treatment and support allows a woman with Turner syndrome to lead a normal, healthy and happy life.

Clinical Trials

A list of ongoing clinical trials is available at: Turner syndrome trials

Research

Current Research

• A study is underway to determine whether the frequency of venous thrombosis is higher in patients with Turner Syndrome versus the general population. ^[2]
• The efficacy of oxandrolone (an anabolic steroid) on the rate of growth when the drug is given to Turner syndrome patients who are also given growth hormone. ^[3]
• An ongoing study is evaluating the dimensions of the aorta and risk of conditions such as aortic dilation in girls with Turner syndrome. ^[4]
• The effect of an androgen type hormone on growth and visual spatial problems is evaluated in patients with Turner syndrome. ^[5]

Recent discoveries

• Guidelines for the use of estrogen replacement therapy (transdermal) are provided. ^[6]
• The risk factors for aortic dilation (which increases the risk for aortic dissection) in Turner syndrome are discussed. The syndrome itself is a risk factor for aortic dilation as is growth hormone use and the presence of a bicuspid aortic valve. ^[7]
• The need for focused screening of the aortic valve and aortic root in patients with Turner syndrome and the benefits of early diagnosis of abnormal valve structure and aortic root dilation are discussed. ^[8]

History

Turner syndrome was named for Dr. Henry H. Turner, an endocrinologist who described, in 1938, similarities between a number patients between the ages of 15 and 23, who were referred for dwarfism and lack of sexual development. The X chromosomal abnormality was not described until thirty years later.

Social Issues

Although the intelligence of people with Turner syndrome is usually normal (within the same range of the general population), they may struggle with nonverbal memory and are challenged by spatial processing (seeing objects in relation to each other). These issues may cause difficulty in math, directions, and problem solving. These deficiencies vary in degree in each person with Turner syndrome but usually have some impact on social relationships in the day to day environment.

References

1. ↑ Papp C, Beke A, Mezei G, Szigeti Z, Bán Z, Papp Z. Prenatal diagnosis of Turner syndrome: report on 69 cases. J Ultrasound Med. 2006 Jun;25(6):711-7; quiz 718-20. Abstract
2. ↑ ClinicalTrials.gov. Venous Thrombosis in Turner Syndrome
3. ↑ ClinicalTrials.gov. Oxandrolone Compared With a Placebo on Growth Rate in Girls With Growth Hormone-Treated Turner's Syndrome
4. ↑ ClinicalTrials.gov. Aortic Dimensions in Turner Syndrome
5. ↑ ClinicalTrials.gov. The Effect of Androgen and Growth Hormone on Height and Learning in Girls With Turner Syndrome
6. ↑ Davenport ML. Moving Toward an Understanding of Hormone Replacement Therapy in Adolescent Girls: Looking through the Lens of Turner Syndrome. Ann N Y Acad Sci. 2008 Jun;1135:126-37. Abstract
7. ↑ Lopez L, Arheart KL, Colan SD, et al. Turner syndrome is an independent risk factor for aortic dilation in the young. Pediatrics. 2008 Jun;121(6):e1622-7. Epub 2008 May 26. Abstract | Full Text
8. ↑ Sachdev V, Matura LA, Sidenko S, et al. Aortic valve disease in Turner syndrome. J Am Coll Cardiol. 2008 May 13;51(19):1904-9. Abstract

External Links

The Magic Foundation

The Human Growth Foundation

National Organization for Rare Disorders