Turner syndrome is a chromosomal disorder affecting the equivalent of one in 2,500 girls, producing a number of features including short stature, failure to enter puberty and infertility.
What is Turner syndrome?
Turner syndrome is a genetic disorder affecting one of the female sex chromosomes. Chromosomes contain a detailed plan of our genetics, inherited from both parents, and each cell in our body has 23 pairs. One pair is the sex chromosomes and determines the baby’s sex – boys have an X and a Y chromosome (XY) whilst girls have two X chromosomes (XX).
Abnormality in one of the two X chromosomes in girls causes Turner syndrome. In around 50% there is an entire X chromosome missing (see figure), or chromosome parts may be missing or rearranged. Sometimes the X chromosome is missing from only some cells. This is known as mosaicism and girls may show only mild features of Turner syndrome, depending on how many of the cells are affected.
What causes Turner syndrome?
The cause is unknown but occurs very early in pregnancy.
What are the signs and symptoms of Turner syndrome?
Although many signs and symptoms are described in Turner syndrome, these vary widely between individuals. Often the diagnosis is only made during investigations for short stature or delayed puberty.
In infancy, Turner syndrome girls can have puffy hands and feet (lymphoedema). Other features include short (webbed) neck, low hairline, a high arched palate and widely spaced nipples giving a shield-like chest appearance. There can also be an increased number of moles and abnormal fingernails.
The most serious problems involve the heart such as narrowing of the main artery (aorta) from the heart, known as coarctation, and heart valve defects. There can also be defects in the kidneys which appear at birth. However, these are not seen in every case. Repeated ear infections and glue ear are very common as are minor vision problems including squints, drooping eyelid (ptosis) and colour blindness. Learning difficulties are not a feature of Turner syndrome although problems with non-verbal skills are common. Affected girls are on average 20cm (eight inches) shorter than expected. Small size may be apparent from birth or in the first years of life.
Although ovaries are present at birth, these soon begin to fail, leading to ‘streak ovaries’. This causes underproduction of the female hormone oestrogen required for puberty, and also the failure to produce mature eggs, leading to infertility. A long-term lack of oestrogen may lead to brittle bones (osteoporosis).
How common is Turner syndrome?
Turner syndrome only affects girls. It is a genetic condition and therefore present at birth. Although Turner syndrome affects one in 30 female foetuses conceived, there is a very high miscarriage rate of affected pregnancies and Turner syndrome is found in one in 2,500 of live-born girls.
Is Turner syndrome inherited?
In the vast majority of girls, there are no other affected family members and it occurs only occasionally. One of each chromosome pair comes from either parent and in 80% of cases the missing X-chromosome comes from the father.
How is Turner syndrome diagnosed?
The diagnosis of Turner syndrome is made by chromosomal analysis or karyotyping, and involves a blood test. The results of this test can take up to six weeks. This, and follow-up testing, can be done as an outpatient.
Karyotyping can also be performed during pregnancy if there are significant concerns. This is done by analysing the fluid surrounding the foetus (amniocentesis) and is done as an inpatient. Associated complications are screened for at diagnosis and then from time to time afterwards as an outpatient.
How is Turner syndrome treated?
Treatment of Turner syndrome depends on the symptoms the child shows. Health professionals from different specialities deal with any disorders of the heart, kidney, ears and eyes. Some physical features of Turner syndrome are purely cosmetic and do not need treatment. Psychological support may assist with educational or social difficulties.
Patients are mainly treated as outpatients. Endocrinologists are involved in three main areas:
- Growth – Most girls require a daily injection of growth hormonewhich improves final height by an average of 7.5cm (three inches). This is usually given from diagnosis or within the first years of life and continues until final height is achieved. Girls who benefit most from this treatment are those who start growth hormone early or are very short to begin with. The results of growth hormone treatment can vary with some girls getting more benefit than others. Often a mild anabolic steroidcalled oxandrolone (taken by mouth) is added in from nine years of age to promote the effect of growth hormone.
- Puberty – Absent puberty is very common in girls with Turner syndrome. Treatment involves the female hormone oestrogen with gradually increasing doses over several years, given by mouth from 12 or 14 years of age. This helps in breast development and maturation of the uterus, leading to periods (menarche). Once the periods have started, they are usually maintained by hormone replacement of oestrogen and the other female hormone progesteroneusing either the oral contraceptive pill or hormone replacement therapy.
- Fertility– Because streak ovaries don’t produce eggs, women with Turner syndrome are infertile and require not only hormone therapy but also egg donation and IVF treatment to fall pregnant. This is carried out through a specialist fertility service.
Are there any side-effects to the treatment?
Growth hormone is generally well tolerated but needs to be given daily by injection and as any other medicine can have side-effects. Rare symptoms include headaches, visual disturbances, hip or knee pain and painful or enlarging moles. Growth hormone may also increase the higher risk of type 2 diabetes and lipid disturbances.
In low doses, oxandrolone has few side-effects. At higher doses, it can produce abnormal liver function and also deepening of the voice, but at usual doses, these are not often a problem.
Although the oral contraceptive pill is widely taken, it does have side-effects in a few individuals such as nausea, vomiting, weight gain, gallstones, high cholesterol, high blood pressure and increased risk of blood clots.
What are the longer-term implications of Turner syndrome?
All people with Turner syndrome should lead a healthy lifestyle throughout their life to reduce long-term risks. They should have regular check-ups during adult life, ideally in a specialist Turner syndrome clinic. Adult women with Turner syndrome are more likely to have a number of health issues including high blood pressure and diabetes. Repeated ear infections may lead to deafness, if not adequately treated.
Problems with non-verbal skills can give rise to difficulties with arithmetic, constructional tasks and a sense of direction. This may make it harder to learn to drive or read maps.
Whilst unassisted pregnancy is rare, women with Turner syndrome can become pregnant and have babies with IVF using eggs donated from other women. Success with fertility treatment is similar to other cases of ovarian failure.