Definition of Turner Syndrome
Turner syndrome or Ullrich–Turner syndrome (also known as “Gonadal dysgenesis”, 45,X, encompasses several conditions in human females, of which monosomy X (absence of an entire sex chromosome, the Barr body) is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent (unaffected humans have 46 chromosomes, of which two are sex chromosomes). Normal females have two X chromosomes, but in Turner syndrome, one of those sex chromosomes is missing or has other abnormalities. In some cases, the chromosome is missing in some cells but not others, a condition referred to as mosaicism or “Turner mosaicism”.
Occurring in 1 in 2000 – 1 in 5000 phenotypic females, 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 autoimmune diseases.Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and memory areas.
Cause of Turner Syndrome
Turner’s syndrome is caused by the absence of two complete copies of the X chromosome in some, or all the cells. The abnormal cells may have only one X (monosomy) (45,X) or they may be affected by one of several types of partial monosomy like a deletion of the short p arm of one X chromosome (46,XdelXp) or the presence of an isochromosome with two q arms (46XiXq) In mosaic individuals, cells with X monosomy (45,X) may occur along with cells that are normal (46,XX), cells that have partial monosomies, or cells that have a Y chromosome (46,XY). The presence of mosaicism is estimated to be relatively common in affected individuals (67-90%).
In the majority of cases where monosomy occurs, the X chromosome comes from the mother. This may be due to a nondisjunction in the father. Meiotic errors that lead to the production of X with p arm deletions or abnormal Y chromosomes are also mostly found in the father. Isochromosome X or ring chromosome X on the other hand are formed equally often by both parents. Overall, the functional X chromosome mostly comes from the mother.
Signs and Symptoms Turner Syndrome
The following is a list of common symptoms of Turner syndrome. It is important to note that an individual may have any combination of symptoms and would unlikely have all symptoms.
- Short stature
- Lymphedema (swelling) of the hands and feet
- Broad chest (shield chest) and widely spaced nipples
- Low hairline
- Low-set ears
- Reproductive sterility
- Rudimentary ovaries gonadal streak (underdeveloped gonadal structures that later become fibrosed)
- Amenorrhoea, or the absence of a menstrual period
- Increased weight, obesity
- Shield shaped thorax of heart
- Shortened metacarpal IV
- Small fingernails
- Characteristic facial features
- Webbed neck from cystic hygroma in infancy
- Coarctation of the aorta
- Bicuspid aortic valve
- Horseshoe kidney
- Visual impairments sclera, cornea, glaucoma, etc.
- Ear infections and hearing loss
- High waist-to-hip ratio (the hips are not much bigger than the waist)
- Attention Deficit/Hyperactivity Disorder or ADHD (problems with concentration, memory, attention with hyperactivity seen mostly in childhood and adolescence)
- Nonverbal Learning Disability (problems with math, social skills and spatial relations)
Other features may include a small lower jaw (micrognathia), cubitus valgus, 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, therefore, no two individuals will share the same features.
Risk Factors for Turner Syndrome
In the majority of cases where monosomy occurs, the X chromosome comes from the mother. This may be due to a nondisjunctionin the father. Meiotic errors that lead to the production of X with p arm deletions or abnormal Y chromosomes are also mostly found in the father. Isochromosome X or ring chromosome X on the other hand are formed equally often by both parents. Overall, the functional X chromosome mostly comes from the mother.
Diagnosis of Turner Syndrome
Turner syndrome may be diagnosed by amniocentesis or chorionic villus sampling during pregnancy.
Often, fetuses with Turner syndrome can be identified by abnormal ultrasound findings (i.e., heart defect, kidney abnormality, cystic hygroma, ascites).
An increased risk of Turner syndrome may also be indicated by abnormal triple or quadruple maternal serum screen. The fetuses diagnosed through positive maternal serum screening are more often found to have a mosaic karyotype than those diagnosed based on ultrasonographic abnormalities, and conversely those with mosaic karyotypes are less likely to have associated ultrasound abnormalities.
Although the recurrence risk is not increased, genetic counseling is often recommended for families who have had a pregnancy or child with Turner syndrome.
Turner syndrome can be diagnosed postnatally at any age. Often, it is diagnosed at birth because of heart problems, an unusually wide neck or swelling of the hands and feet. However, it is also common for it to go undiagnosed for several years, typically until the girl reaches the age of puberty/adolescence and she fails to develop properly (the changes associated with puberty do not occur). In childhood, a short stature can be indicative of 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.
Prevention from Turner Syndrome
Treatment of Turner Syndrome
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 such as the birth control pill, 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, cardiovascular health and tissue health. Women with Turner Syndrome who do not have spontaneous puberty and who are not treated with estrogen are at high risk for osteoporosis and heart conditions.
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.
Uterine maturity is positively associated with years of estrogen use, history of spontaneous menarche, and negatively associated with the lack of current hormone replacement therapy.