What Is Turner Syndrome? What Causes Turner Syndrome?

Turner syndrome, also known as Turners syndrome, Ullrich-Turner syndrome or Gonadal dysgenesis, is a chromosomal disorder that affects only females. It is characterized by the absence of part or all of a second sex chromosome in some or all cells. Approximately 1 in every 2,500 to 3,000 girls is born with the condition.

People without Turner syndrome have 46 chromosomes, of which 2 are sex chromosomes. Females have two X chromosomes. In people with Turner syndrome, one of those sex chromosomes is either missing or has other abnormalities - the chromosome may be missing in some cells but not in others (mosaicism or Turner mosaicism). In other words, there are two types of Turner syndromes:

Classical Turner syndrome - an X chromosome is completely missing.

Mosaic Turner syndrome (mosaicism or Turner mosaicism) - the abnormalities only occur in the X chromosome of some of the cells in the body.

Chromosomes are strands of DNA (deoxyribonucleic acid) that exist in all the cells of the human body. Chromosomes contain instructions that make a human's behavioral and physical characteristics.

The syndrome is named after Dr. Henry Turner (USA 1892-1970), an Oklahoma endocrinologist, who described it in 1938.

Turner syndrome can cause:

Physical disabilities
Emotional disabilities
Educational disabilities

According to Medilexicon's medical dictionary:

Turner syndrome is "a syndrome with chromosome count 45 and only one X chromosome; buccal and other cells are usually sex chromatin-negative; anomalies include dwarfism, webbed neck, valgus of elbows, pigeon chest, infantile sexual development, and amenorrhea; the ovary has no primordial follicles and may be represented only by a fibrous streak; some affected people are chromosomal mosaic, with two or more cell lines of different chromosome constitution; seen in many animal species, in the meadow vole it is the normal female state."

What are the signs and symptoms of Turner syndrome?

A symptom is something the patient feels and reports, while a sign is something other people, such as the doctor detect. For example, pain may be a symptom while a rash may be a sign.

The signs and symptoms of Turner syndrome vary considerably and may even appear before birth.

Signs and symptoms before birth

Unborn females with Turner syndrome (TS) may develop lymphedema - fluid is not properly transported around the organs of the body, excess fluid leaks into the surrounding tissue, resulting in swelling. It is not uncommon for babies born with TS to have swollen hands and feet. The unborn baby may also have:

• Thick neck tissue
• Cystic hygroma - swelling of the neck
• Lower than normal weight

The following signs and symptoms may be present at birth or during infancy

• Broad chest
• Cubitus valgus (arms turn outwards at the elbows)
• Eyelids that droop
• Fingernails that turn upward
• High, narrow palate (roof of mouth)
• Low hairline at the back of the head
• Low set ears
• Receding lower jaw
• Short hands
• Slower/delayed growth
• Small lower jaw
• Smaller height at birth
• Smaller weight at birth
• Swelling of the hands and feet
• Web-like neck
• Wide neck
• Widely spaced nipples

In some cases Turner syndrome may not become apparent until later on. The following signs and symptoms that appear later may indicate Turner syndrome:

• Growth spurts do not occur at expected childhood times. During the first three years of life the baby/toddler may be of normal height. However, by the age of three their growth rate will be lower than average.
  
  The person is much shorter than expected; about 8 inches (20 cms) shorter than expected for an adult female member of that family (without treatment).
• Learning difficulties - the majority of girls with TS have normal intelligence, as well as good verbal and reading skills. There may be some problems with math, spatial concepts, memory skills and fine finger movements.
• Social problems - the patient may find it hard to properly interpret other people's reactions or emotions.
• Non-functioning ovaries - during puberty a female's ovaries generally start producing estrogen and progesterone (sex hormones). The majority of girls with TS will not produce these sex hormones, resulting in:
  
  
  • No onset of menstrual periods
  • Poorly developed breasts
  • Possible infertility
  Although the TS female has non-functioning ovaries and is infertile, her vagina and uterus (womb) will generally be normal and she will usually be able to have a normal sex life. Approximately 30% of females with TS will undergo some physical changes during puberty. About 0.5% of girls with TS can become pregnant without fertility treatment.

Other possible signs and symptoms - as well as those listed above, the following may also be present:

• Eyes that slant downwards
• Prominent earlobes
• Mouth abnormalities which can cause dental problems
• Narrowing of the aorta which may result in heart murmur
• Hypothyroidism - an underactive thyroid gland. This can be treated with thyroxine tablets.
• Hypertension - females with TS are more likely to suffer from high blood pressure
• Brittle bones (osteoporosis) - caused by insufficient estrogen
• Otitis media (middle ear infection, glue ear) - very common among young girls with TS
• Hearing loss in adulthood - usually caused by otitis media during childhood
• Diabetes - older and overweight females with TS have a higher risk of developing diabetes compared to other women of the same age or weight
• Moles - females with TS may have a large number of moles
• Small spoon-shaped nails
• A shorter than normal fourth finger or toe

What are the causes of Turner syndrome?

Experts say that the loss or abnormality of the X chromosome occurs spontaneously. If somebody has a child with TS, this does not mean there is a higher risk of any subsequent children having the condition.

TS occurs when the baby is conceived, when the sperm enters the egg (ovum) and the egg is fertilized.

Only females are affected.

TS occurs when the second X chromosome is either incomplete or missing completely.

According to the National Health Service (NHS), UK, about 1 in every 2,500 baby girls is born with the condition. If a baby is conceived with a missing X chromosome the pregnancy usually miscarries (aborts naturally).

Approximately 10% of all miscarriages during the first trimester of pregnancy are caused by TS.

Most of us are born with two sex chromosomes. Males inherit the X chromosome for their mothers and the Y chromosome from their fathers. Females inherit one X chromosome from each parent. When a female has Turner syndrome one X chromosome copy is either absent or significantly altered. The following genetic alterations of Turner syndrome are possible:

• Monosomy - one X chromosome is completely missing. Experts believe this is caused by an error either in the father's sperm or the mother's ovum (egg). Every cell in the offspring's body has one X chromosome missing.
• Mosaic Turner syndrome (mosaicism or Turner mosaicism) - during the early stages of fetal development an error may have occurred in cell division, resulting in some cells having two X chromosome copies, while others only have one. In some cases there may be some cells with both X chromosome copies, and others with one altered copy.
• Y chromosome material - a small number of patients with TS have some cells with just one X chromosome copy and other cells with just one X chromosome copy as well as some Y chromosome material. The individual develops as a female, but has a higher risk of developing gonadoblastoma (a type of cancer).

The missing or altered X chromosome causes errors during fetal development, as well as subsequent development after birth.

What are the risk factors for Turner syndrome?

A risk factor is something which increases the likelihood of developing a condition or disease. For example, obesity significantly raises the risk of developing diabetes type 2. Therefore, obesity is a risk factor for diabetes type 2.

Experts say that the risk of having TS is the same for females in all regions of the world, races, nationalities and socioeconomic groups. The condition occurs randomly and is not associated with the age of the mother or father.

There are no known toxins or environmental factors that appear to alter the risk of developing TS.

How is Turner syndrome diagnosed?

Diagnosis during pregnancy and birth - during an ultrasound test, for example, TS may be suspected. Amniocentesis or Chorionic villus sampling, both antenatal tests that detect chromosomal abnormalities, are possible ways to confirm a diagnosis. Diagnosis may also eventually be made if heart or kidney problems, or swelling of the hands and feet are present at birth.

Diagnosis during childhood - if the child has a wide or webbed neck, a broad chest and widely spaced nipples TS may be suspected.

If the girl eventually has a short stature and undeveloped ovaries, TS may be suspected.

Sometimes diagnosis is not made until later, for example, when puberty does not occur.

Karotype - this blood test can be used to detect extra or missing chromosomes, chromosomal rearrangements, or chromosomal breaks. This may be done either by taking a sample of the amniotic fluid while the baby is still in the uterus, or taking a blood sample from a child/baby. If one of the X chromosomes is missing or incomplete, TS is confirmed.

What are the treatment options for Turner syndrome?

Turner syndrome is a genetic condition for which there is no current cure. However, several treatments may help with short stature, sexual development and learning difficulties.

Early preventative care - it is important that the child is checked regularly so that the risk of complications can be minimized. Blood pressure and the thyroid gland need to be monitored frequently, and any necessary treatment given immediately.

Treatment with medical specialists - as girls with TS are more likely to develop otitis media (inner ear infections, glue ear) they need to be treated promptly to minimize the risk of hearing difficulties later in life. Treatment should be carried out by an ENT (ear, nose and throat) specialist.

Hormone therapy, which may include estrogen, progesterone and growth hormones, may be required. These treatments will be done with an endocrinologist, or pediatric endocrinologist.

Growth hormone therapy - as soon as it is established that the girl with TS is not growing properly growth hormone should be administered. Effective therapy may prevent short stature later in life. Treatment may start as early as the age of one or two years. A daily injection is given. Growth hormone therapy may add an extra 10cm (4 inches) to the girl's eventual stature.

Estrogen and progesterone replacement therapy - the girl needs these two hormones to develop sexually. Estrogen will also stop her bones from becoming brittle (osteoporosis). The ovaries of a girl with TS do not produce sufficient quantities of these hormones. How much the patient is producing herself can be determined with blood tests.

Estrogen replacement therapy will start at the onset of puberty (11 years of age). The patient will initially receive low doses, which are slowly increased. Progesterone therapy is generally given later to trigger menstrual periods. TS patients require sexual hormone treatment for the rest of their lives. Treatment may be given as tablets, injections or patches.

IVF (in vitro fertilization) - the majority of patients with TS are unable to become pregnant without help. If a woman with TS wants to become pregnant she will probably require assistance, for example, IVF. If the patient manages to become pregnant she will need to be monitored closely, because of the extra strain on her heart and blood vessels.

Counseling and psychological therapy - some patients may develop psychological problems and will benefit from psychological therapy.

Learning assistance - although girls with TS generally have normal levels of IQ, there may be problems with numeracy, spatial concepts, memory skills and fine finger movements. Educational support will help the child.

What are the possible complications related to Turner syndrome?

Heart problems - some girls with TS are born with either heart defects or very slight heart abnormalities which may raise their risk of complications later in life. Defects in the aorta, the main blood vessel leading out of the heart raises the risk of aortic dissection (a tear in the inner layer of the aorta). If there is a defect in the valve between the aorta and the heart there is an increased risk of an aortic valve stenosis (narrowing of the valve).

High blood pressure - people with TS are much more prone to suffer from high blood pressure (hypertension) compared to others.

Diabetes - overweight or older women with TS have a higher risk of developing diabetes compared to other women of the same age and weight.

Hearing - gradual loss of nerve function can cause hearing loss. Girls with TS are much more likely to develop glue ear (otitis media, inner ear infection), which can lead to hearing loss.

Kidney problems - approximately 30% of TS patients have some kind of kidney malformation, raising the risk of hypertension and urinary tract infections.

Hypothyroidism - having an underactive thyroid gland is more likely among patients with TS.

Tooth loss - patients with TS have a higher risk of having poor or abnormal tooth development, resulting in more tooth loss. Also, because of the shape of the mouth and palate, the patient is more likely to suffer from crowded and poorly aligned teeth.

Vision - strabismus is more common among girls with Turner syndrome (eyes to not work in parallel and appear to be looking in different directions). Hyperopia (farsightedness, long-sightedness) is more common among girls with TS.

Bones - women with TS have a significantly higher risk of developing osteoporosis. Sometimes there may be problems with the curvature of the spine, leading to scoliosis. There is also a risk of kyphosis (forward rounding of the upper back).

Pregnancy - a woman with TS who becomes pregnant has a significantly higher risk of developing complications, including gestational diabetes, high blood pressure and aortic dissection.

Psychology - there is a greater risk of problems with self-esteem, anxiety, depression, ADHD (attention deficit hyperactivity disorder). There may also be difficulties in social situations.