What is Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)?
Turner syndrome, sometimes known as ‘congenital ovarian hypoplasia syndrome’, was first identified by a doctor called Henri Turner from Oklahoma in 1938. It is the most frequently occurring abnormality in females that’s related to sex chromosomes. This syndrome develops when one of a female’s X chromosomes is either partially or completely missing.
What Causes Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)?
Turner syndrome happens when one copy of the female X chromosome is either missing or not working properly. About half of people with Turner syndrome have only one fully functioning X chromosome (a condition called monosomy X). The other half have a mix of normal cells and cells with only one X chromosome (a condition known as mosaicism).
There are several ways an X chromosome can become non-functional, including:
* Isochromosome Xq: This is when the chromosome has two copies of its long section, connected at the tips.
* Ring chromosome: In this case, parts of the chromosome’s short and long sections are missing.
* Xp or Xq deletion: This happens when a part of the short part of the X chromosome is missing.
Some people with Turner syndrome might also have a mix of cells with a Y chromosome. Even though this isn’t a cause of Turner syndrome, it can still happen.
A gene called SHOX (short stature homeobox-containing gene on the X- chromosome) is linked to the shorter height often seen in people with Turner syndrome.
It’s important to note that Turner syndrome isn’t usually inherited. It’s a random occurrence that happens during reproduction.
Risk Factors and Frequency for Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)
Turner syndrome occurs in approximately 1 in 2000 to 1 in 2500 live female births, according to medical literature. However, the actual figure might be higher because the condition often goes unnoticed, particularly in mild cases. This can lead to delayed diagnosis until adulthood. It’s worth noting that Turner syndrome is almost equally prevalent across various ethnicities and countries. Interestingly, due to increased use of prenatal ultrasound scans, fewer babies are being born with Turner syndrome, as some pregnancies where the baby has the syndrome are terminated.
Signs and Symptoms of Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)
Turner syndrome is a condition that primarily affects females. It can be identified before birth through ultrasound findings like the swelling at the back of the neck, heart problems, kidney abnormalities, and excessive or decreased amniotic fluid. After birth, girls with Turner syndrome might have swelling of the hands and feet, a web-like appearance of the neck due to extra folds of skin, atypical nail growth, a very small indentation at the roof of the mouth, and unusually short fingers or toes.
As these girls grow, they often have shorter height, chest shaped like a shield with widely spaced nipples, more skin folds on the neck, low hairline at the back of the neck, an inward bend of the elbow, and a wrist and forearm condition called Madelung deformity.
Although people with Turner syndrome generally have average intelligence, they might have certain cognitive impairments like issues with comprehension of spatial and numerical information. This can lead to learning difficulties, particularly in math, memory, and attention. During their teenage years, they may experience puberty delay or absence of menstrual periods due to premature failure of the ovaries. The ‘streak gonads’, a feature of Turner syndrome, are essentially underdeveloped ovaries consisting mostly of connective tissue and no egg-producing follicles.
People with Turner syndrome have a greater likelihood of developing heart defects, which increases their risk of early mortality. Such heart defects include a defective aortic valve, elongated aortic arch, and anomalies in the pulmonary veins. Aortic dissection, a serious condition where the large blood vessel branching off the heart tears, further amplifies the death risk in these individuals.
Frequent ear infections leading to hearing loss are common in Turner syndrome, either due to problems with the middle ear or due to defects in the cells in the inner ear that help to transmit sound. These individuals are also susceptible to kidney-related abnormalities.
Eye-related abnormalities associated with Turner syndrome include being nearsighted or farsighted, misalignment of the eyes, lazy eye, fold of the skin at the inner corner of the eye, drooping eyelids, wide set eyes, and red-green color blindness. People with Turner syndrome are more likely to have autoimmune disorders, including underactive thyroid, celiac disease, and inflammatory bowel disease. Females with Turner syndrome, due to their underdeveloped gonads, have a raised risk of developing a type of tumor called gonadoblastoma.
Testing for Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)
Turner syndrome can be detected before a baby is born through tests like sampling of the chorionic villus or amniocentesis. These methods are recommended if a pregnancy ultrasound reveals signs such as unusual fluid buildup in the fetus, a cyst-like growth in the neck, or heart defects. To confirm the diagnosis after the baby is born, a karyotype test is done. A karyotype test looks at the number and structure of a person’s chromosomes. Sometimes, the karyotype might appear normal, especially in cases of mosaicism where not all cells have the same genetic makeup. If this happens, but the doctor strongly suspects Turner syndrome, a FISH study which is a type of genetic test, might be done along with the karyotype test.
During teenage years, girls with Turner syndrome will likely have puberty delays or an absence of menstruation. High levels of a hormone called follicle-stimulating hormone (FSH) could hint towards Turner syndrome. Hormone called anti-Mullerian hormone (AMH) might be an even better indicator for predicting if a girl will fail to develop ovaries normally. If Turner syndrome is suspected but the initial karyotype is normal, a second karyotype can be done using different body tissues like skin, cheek cells, or cells lining the bladder.
Once Turner syndrome has been diagnosed, there will be assessments for other possible abnormalities, like issues with the heart, kidney, and learning disabilities that might be associated with Turner syndrome. Screenings will be scheduled initially and then performed after regular durations. At the time of diagnosis, patients might have to undergo tests to image the kidney and ascertain heart health, including echocardiography (a type of ultrasound) in infants and children, and MRI in older girls and women.
Below is a list of some of the routine tests for Turner syndrome:
At four years of age or older: TSH blood test to check for autoimmune thyroiditis, a condition where the immune system attacks the thyroid gland, and a tissue transglutaminase with total IgA test to check for celiac disease, a disorder that damages the small intestine.
At ten years of age or older: Fasting blood glucose, glycated hemoglobin, ALT, AST, Serum creatinine, and urinalysis to check for conditions like diabetes, fatty liver, and kidney disease.
Treatment Options for Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)
Girls with a condition called Turner syndrome are usually quite short. While short stature isn’t caused by a lack of growth hormones in these individuals, treatment with growth hormones can be extremely beneficial. This can be started if a girl’s height falls below the lower 5% for her age. Without proper treatment, her adult height might be around 20cm less than the average height for adult women. The use of growth hormones should continue until the girl has reached her adult height and is not expected to grow anymore. However, growth hormone treatment can sometimes reveal an issue with the spine called scoliosis. Therefore, careful monitoring of the spine is necessary during this treatment. If scoliosis does emerge, referral to a specialist in bone and muscle conditions is recommended to explore possible brace or surgery options. There may be some side effects of growth hormone treatment such as increased pressure in the brain, slips at the femoral growth plates and inflammation of the pancreas. Furthermore, if a girl requires more help to grow in addition to growth hormones, other treatments like oxandrolone or late puberty induction can be considered.
Heart abnormalities are often seen in girls with Turner syndrome. Therefore, at diagnosis, heart health should be assessed by a heart specialist using an EKG to check for extended gaps between heartbeats (prolonged QT interval). It’s also important to compare blood pressure in the arms and legs and to use an echocardiogram (ECG) or cardiac MRI to look for other heart abnormalities. Certain medications can lengthen the QT interval and should be avoided in these patients. An issue with the main blood vessel that carries blood from the heart (the aorta) could require corrective surgery. These girls must have regular monitoring of the aorta for its dilation and blood pressure should be controlled using medications like beta-blockers or ACE inhibitors, if necessary.
Despite having a normal intelligence level, girls with Turner syndrome oftentimes have learning difficulties that may require special schooling and assessments. Frequent hearing checks, every three years in children and every five years in adults, should be performed because these girls are at a high risk of hearing loss. Moreover, Turner syndrome is often associated with kidney abnormalities such as misshapen kidney, fused kidneys and improper kidney rotation. In these cases, consultation with a kidney specialist will be required.
In Turner syndrome, the onset of periods and development during puberty may be delayed due to an early failure of the ovaries. This condition should be investigated beginning from the age of 10-11 years. While the majority of girls with Turner syndrome will require estrogen therapy, it’s important for them to stay in touch with their doctor and follow the provided guidelines. Turner syndrome patients also have the option for preserving ovarian tissues or eggs, though this treatment is typically recommended only for those with evidence of normal ovarian function and not recommended prior to the age of 12.
Bone health can be an issue for these girls due to an increased risk of low bone density and fractures. Their risk improves with estrogen therapy, along with vitamin D and calcium supplements. Turner syndrome also increases the risk of scoliosis, a spine curvature, so regular check-ups are recommended, especially during growth hormone therapy. Lastly, girls with Turner syndrome should be screened for several other potential health conditions like celiac disease, autoimmune thyroiditis, liver disease, metabolic syndrome, and vitamin D deficiency at regular intervals. Moreover, if the Y chromosome or signs of virilization (development of male physical characteristics) are seen, the gonads (organs that produce reproductive cells) should be removed due to an elevated risk of gonadoblastoma, a type of tumour.
What else can Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome) be?
Noonan syndrome and Turner syndrome are two conditions that can be quite tricky to tell apart because they display similar symptoms. These symptoms can include a short stature, a webbed neck, and issues with the heart and kidneys. However, there’s a significant difference between the two. While Turner syndrome, which only occurs in females, involves a missing or non-functioning X chromosome, Noonan syndrome doesn’t involve any chromosomal abnormalities. This factor means that both males and females can have Noonan syndrome. To correctly identify which of the two conditions a patient has, doctors need to perform genetic testing.
What to expect with Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)
People with Turner syndrome have a mortality rate three times higher than the average person. A leading cause of this increased mortality rate is cardiovascular disease, specifically coronary heart disease and stroke, particularly in older patients. Among heart-related diseases present at birth, an aortic aneurysm is the primary threat.
Patients are also at higher risk of death due to pneumonia, diabetes, epilepsy, liver disease, and kidney disease. Overall, Turner Syndrome significantly heightens the risk of various health complications.
Possible Complications When Diagnosed with Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)
Turner syndrome comes with several potential complications and health issues. These include:
- Hearing loss
- Underactive thyroid, also known as hypothyroidism
- Abnormalities in liver function
- Issues with cognitive function, which may require special education programs in school
- An increased risk of autoimmune diseases, where the immune system attacks the body
- The risk of tearing in the main artery of the body, known as aortic dissection
- For women with the Y chromosome, there is an increased risk of gonadoblastoma, a rare type of cancer
- Metabolic disorders which can lead to excessive fat around the waist (central obesity), increased resistance to the hormone insulin, development of type 2 diabetes, and abnormal lipid levels in the blood (dyslipidemia)
Preventing Turner Syndrome (Congenital Ovarian Hypoplasia Syndrome)
Turner syndrome is a condition that someone will have for their entire life, and it needs regular check-ups. This condition comes with several associated health issues. These include being shorter than average, having abnormalities in the heart and kidneys, premature failure of the ovaries (which can cause early menopause), and being more likely to become obese, develop diabetes, or have high blood pressure. As a lot of these issues are complex, multiple specialists will often need to work together to provide the best care possible.
