Turner Syndrome

Turner Syndrome is a condition that affects only girls or women. Most people are born with two chromosomes. While a boy inherits the X chromosome from his mother and Y chromosome from his father, a girl inherits one X chromosome from each parent. In case of Turner syndrome, one copy of the X chromosome is missing or partially missing or is significantly changed.

Named after Henry Turner, the first doctor who reported it in 1938, Turner Syndrome is one of the most common chromosomal disorders and likely the most common genetic disorder of females.

Genetic alterations that causes Turner Syndrome

Monosomy: Complete absence of X chromosome - caused due to an error of father's sperm or in the mother's egg.

Mosaicism: An error that occurs in cell division during early stages of fetal development.

Y chromosome: In a small percentage of Turner Syndrome patients, some cells have only one copy of X chromosome and other cells have one copy of the X chromosome and some Y chromosome material. Though these individuals develop biologically as girls, due to the presence of Y chromosome material increase, the risk of developing a type of cancer called gonadoblastoma is present.

Turner Syndrome can cause a variety of medical problems. Short height, puberty failure, infertility, heart defects and learning disabilities and social adjustment problems are some of the prominent signs of this syndrome. Family history is not a risk factor in this syndrome as it is quite unlikely that parents of one child with this syndrome will have another child with the same disorder.

Prenatal symptoms

Prenatal ultrasound of a baby with Turner Syndrome may reveal:

• Heart abnormalities,
  
• Large or abnormal fluid collection at the back of neck,
  
• Kidney abnormalities.

Physical features of Turner Syndrome at birth and during infancy

A wide neck, receding small lower jaw, high narrow roof of the mouth, low-set ears, low hairline behind neck, broad chest with widely spaced nipples, short fingers and toes, arms that turn outward at the elbows, narrow and upward turned fingernails and toes, swelling of hands and feet at birth, smaller than average height at birth and delayed growth.

Physical features noticeable in girls in teens/ young women

There could be occurrences when Turner Syndrome is not quite apparent. Some noticeable features are: No growth spurts, short stature – less than might be expected for a female member of the family, learning disabilities especially that involve spatial concepts or math, inability to understand other people's emotions and social situations, absence of sexual changes expected during puberty due to ovarian failure, early end to menstrual cycles but not due to pregnancy, lack of sexual development during teenage years, inability to conceive a child without fertility treatment.

Diagnosis

Sometimes even during fetal development, diagnosis of this syndrome can be made. While ultrasound screening may raise suspicion of Turner Syndrome in the baby; prenatal screening tests that evaluate the baby's DNA in the mother's blood could also indicate an increased risk of this syndrome. Other than the characteristic physical features described above, Turner Syndrome may be diagnosed prenatally, before birth, during infancy or in early childhood, although sometimes the diagnosis might be delayed. It is imperative that girls and women with this syndrome undergo ongoing medical care from a variety of specialists and regular checkups and appropriate care are taken.

Clinical testing

Karyotyping is a laboratory test that evaluates the chromosomes which is usually the determining factor for Turner Syndrome. In most cases a blood sample is taken to ascertain a person's karyotype. This syndrome is increasingly diagnosed before birth based on chromosomal analysis subsequent to amniocentesis or Chorionic Villus Sampling CVS. A sample of fluid that surrounds the developing fetus is removed and analyzed. In CVS, it involves the removal of tissue samples from a portion of the placenta. Accumulation of lymph fluid near the neck of a developing fetus can sometimes be seen on a routine fetal ultrasound.

MRI is performed in those affected for the presence of symptoms potentially associated with Turner Syndrome such as liver, kidney and heart abnormalities. Complete cardiac workup including echocardiogram is done to assess the structure and function of the heart. Thyroid and liver function tests, hypertension screening is done. Children and adults require periodic evaluation for hearing also.

Complications arising out of Turner syndrome

Some of the complications arising out of this syndrome include:

Heart defects or slight abnormality in the heart structure that could increase the risk of serious complications. This could be defects in the main blood vessel leading out of the heart or increased risk of a tear in the inner layer of the aorta.

Women with Turner Syndrome can have increased risk of diabetes and high blood pressure. Hearing loss is also common among girls and women with this syndrome. Gradual loss of nerve function could be the reason for hearing loss in some. Slight abnormalities in the shape of the skull could also increase the risk of frequent middle ear infections.

Kidney problems are seen in one-third of girls with Turner Syndrome who have malformation of kidneys. This could increase pressure and urinary tract infections, although they do not necessarily cause medical problems.

Increased risk of certain immune disorders such as hypothyroidism can be seen in some women with this syndrome. This disorder results in low production of hormones that is important for controlling heart rate, growth and metabolism.

Diabetes, inflammatory Bowel Disease and intolerance to wheat are conditions that can be caused by Turner Syndrome. Poor and abnormal tooth development and greater risk of tooth loss or crowded teeth and poorly aligned bite are complications of this syndrome.

Girls with Turner Syndrome pose risk of increased vision problems, due to weak muscle control of eye movements and farsightedness. Bones are bound to get affected by this syndrome, with increased risk of abnormal curvature of the spine and forward rounding of the upper back. Osteoporosis is another common risk of this syndrome.

Though most women with this syndrome are infertile, a small number do get pregnant spontaneously, and others become pregnant with fertility treatment. But, there are instances where women with this syndrome are likely to experience failure of the ovaries and subsequent infertility very early in adulthood. A cardiologist intervention is essential before pregnancy as they are at increased risk of aortic dissection during pregnancy. They are also at increased risk of high blood pressure and gestational diabetes during pregnancy.

Some girls and women do have psychological issues due to Turner Syndrome with disabilities in math and spatial concepts, difficulties in social situations and increased risk of attention-deficit/hyperactivity disorder.

Treatment and medication

Since chromosomal abnormality causes this syndrome, as such there is no specific cure. However, researchers have developed a number of treatments that can help with growth problems. Growth hormone therapy is recommended for most girls with this syndrome. This is done to increase height as much as possible at appropriate times during childhood and teen years. Growth hormone is given by way of injections several times a week and if the height is really short, doctors recommend androgens in addition to growth hormone.

Estrogen therapy is administered in order to begin puberty and achieve adult sexual development. Estrogen is also given along with growth hormone. Estrogen therapy usually continues throughout life until average age of menopause.

In case of some women with Turner Syndrome, they can become pregnant with donation of an egg or embryo. A specially designed hormone therapy is necessary to prepare the uterus for pregnancy. And pregnancy can be high-risk with Turner Syndrome.

Management of Turner syndrome

Those affected are advised regular checkups which can improve the quality and length of life. Periodic checkups for hearing loss, eye problems, high blood pressure and diabetes and osteoporosis are imperative. Follow-up with a heart specialist is essential as are regular ultrasounds of the heart. Healthy lifestyle habits such as maintaining proper weight and exercising regularly are important throughout life.

And, although girls with Turner syndrome exhibit learning disabilities, most can attend school regularly, write well, learn by hearing, can memorize and develop reasonably good language skills.

Tips for those with Turner syndrome

• Stay active in sports or hobbies.
  
• Consider some voluntary work. Helping others can boost your self-esteem.
  
• Talk to a professional therapist.
  
• Discuss your problems with your parents if you think they can help.
  
• Talk to your school counselor in case of any particular problem.
  
• Record your feelings in a journal or diary about the challenges you are coping with.

Monosomy

Monosomy is a rare chromosome anomaly. Human cells normally contain 23 pairs of chromosomes, with a total of 46 chromosomes in each cell. Monosomy refers to the loss of one chromosome in cells. Any such change of chromosomes shall cause problems pertaining to growth, development and function of the body's systems. Monosomy is a genetic defect caused by an incomplete set of chromosomes. The changes in chromosomes occur during the formation of reproductive cells in early fetal development.

Monosomy can be identified during prenatal testing, especially in women who are at high risk. Prenatal testing such as an amniocentesis can reveal monosomy. As the test results could be very complicated, it is important to receive genetic counseling before undertaking this test. While a negative result indicates that no abnormalities were detected, a positive result suggests that a problem may be present. Since false positives and negatives can also happen, follow up additional testing is also recommended.

Aneuploidy is the term used to refer to chromosomal defects, a gain or loss of chromosomes from the normal 46. In monosomy, which is a kind of anueploid, there is the loss of one chromosome in cells. Another common form of aneuploidy is trisomy where people have three copies of a particular chromosome 21 in each cell instead of the two copies. One common example of the condition caused by trisomy is Down Syndrome.

Turner syndrome is a known example of the condition caused by monosomy. In this syndrome, women typically have only one X chromosome instead of the usual two. Significantly, Turner syndrome is the only full monosomy that is found in human beings. In other full monosomy, the individual will not survive development.

Cri du chat syndrome and 1p36 Deletion Syndrome are instances of partial monosomy caused by deletion of the short p arm of chromosome 5 and chromosome 1 respectively.

Chi du chat syndrome is characterized by a number of symptoms and in particular a malformed larynx which causes the voice to sound strangely high pitched. Chromosome 1p36 deletion syndrome is considered one of the commonest chromosome deletion syndromes. It is characterized by features such as developmental delay, feeding difficulties, low muscle tone, distinctive facial features, hearing loss, heart problems, seizures, vision defects and a large fontanelle that is slow to close. The incidence of monosomy 1p36 has been estimated to be 1 in 5000 to 1 in 10000 live born children. Interestingly, more females than males have been reported.

Celiac Disease

Celiac disease is an inherited auto-immune disease that is characterized by diffused damage to the small intestinal mucosa leading to malabsorption of nutrients. The development of Celiac disease is attributed to a combination of genetic (HLA alleles) and environmental (gluten ingestion) factors. Celiac disease patients carry the gene identified as HLA DQ2 and/or HLA DQ8. Approximately 30% - 40% of the population in general carry one or both of these genes out of which about 1-5% are expected to develop Celiac disease. The incidence of disease is on the rise, and September 13 is observed as Celiac Awareness Day across the world.

The damage and the discomfort associated with Celiac disease is triggered by consumption of gluten. Gluten is a protein that is present in certain grains such as wheat, rye, barley but absent in rice, oats and corns. In a genetically susceptible host, gluten stimulates autoimmune responses wherein the body's immune system mounts an attack on its own tissues. Due to damage to the villi in the intestines, there is malabsorption of nutrients from food.

Celiac disease is not the same as gluten intolerance. Celiac disease involves autoimmune reaction to gluten and begins to target its own tissue, whereas gluten intolerance is when ingestion of gluten causes the body to have a stress response that does not involve the immune system. The symptoms of both the conditions may appear identical. However, Celiac disease has severe manifestations and may involve hives and rashes.

In case of Celiac disease, blood test shows the higher the levels of class IgA anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies. Gluten intolerance is marked by gastrointestinal symptoms and no specific immunological mechanisms or serological markers are identified for this condition.

Risk factors

Celiac disease is partly a genetic condition and hence tends to run in families. Individuals with Celiac patient in their immediate family have a higher chance of developing Celiac disease. People with other autoimmune conditions like Type 1 diabetes, Thyroid disorders, Addison's disease and Autoimmune hepatitis are more likely to develop Celiac disease. People with other genetic conditions like Down's syndrome, Williams syndrome and Turner's syndrome are also at higher risk of developing Celiac disease.

Signs and symptoms of Celiac disease

Symptoms range from mild to severe manifestations and vary from adult patients to children. Celiac disease presents itself with both gastrointestinal and extra-intestinal symptoms. Abdominal pain, Type I diabetes, chronic constipation, recurrent non-bloody diarrhea, anemia, delayed puberty are some of the prominent symptoms noticed in children with Celiac disease. Intussusceptions, mouth ulcers, osteoporosis, brain fog, neurological dysfunction, unexpected weight and hair loss, nausea, bloating, anemia, inability to retain the pregnancy, migraines are the signs and symptoms identified with adult Celiac patients.

Diagnosis

Diagnosis of Celiac disease is always a two step procedure - beginning with tTG-IgA and total serum IgA tests and conforming it with intestinal biopsy. The diagnosis is never based only on serology as anti tTG may be high in others diseases like inflammatory bowel disease and chronic liver disease. In addition, serology may be negative in patients with low IgA levels, or in children less than 2-3 years. Along with blood tests, genetic tests may also be ordered to check for the presence of the gene HLA DQ2 or HLA DQ8 in an individual. Almost all Celiac disease patients carry one of these genes. Finally the disease is confirmed by performing intestinal biopsy.

There have been recent guidelines by world renowned medical institutions that immediate family members should be screened for the disease as Celiac disease is genetic and other immediate blood relations in the family have a higher probability of developing Celiac disease than the general population. They should be screened at the time the index patient is diagnosed and thereafter, if they exhibit any symptoms, or at least annually. Early diagnosis can help prevent complications.

Treating Celiac disease

Right now, the only treatment for Celiac disease is to strictly adhere to lifelong gluten-free diet. Fruits, vegetables, dairy, fish and other seafood, beans, legumes can be safely consumed as all of these are gluten-free food groups. Grains such as rice, corn, quinoa, millet, teff, flax, chia and starchy roots like tapioca, potato are all gluten-free.

Avoiding gluten completely is not easy. Any occasional slip leads to a flare-up of symptoms instantly. Considering the fact that there are numerous cases of Celiac disease every year and the increasing numbers, there is serious research being conducted to come up with drug therapy. New drug treatments for Celiac disease are now being tested in clinical trials - some are designed to be taken alongside a gluten-free diet, whereas other set of medicines free the patient from all diet restrictions. Three main approaches have been proposed as new therapeutic modalities that include: gluten detoxification, inhibition of intestinal permeability and modulation of immune response.

Currently there are three drugs that are under clinical trails and seem to be successful in treating the condition.:

ALV003: It contains the enzymes that chop up gluten before it starts to activate the immune system.

AN-PEP: An enzyme that breaks down the residual gluten in the stomach.

Larazotide Acetate: May help inhibit immune reaction by blocking a protein that carries pieces of gluten across the gut.

However these drugs still require medical approval to be commercially available in the market.