Turner syndrome or Ullrich syndrome also known as gonadal dysgenesis actually encompasses many alterations of which the absence of the entire X chromosome is very common. This condition of loss of whole X chromosome is also known as monosomic condition. Turner syndrome is a chromosomal abnormality where all or few parts of the sex chromosome are missing. In general females carry two X chromosomes but in this syndrome either one of these precious chromosomes is missing or some other abnormalities are there. In some cases the chromosomes are missing in some cells but not in others then this condition is recognized as mosaicism or Turner mosaicism. The probability of occurrence of this syndrome is 1 in 2000 to 1 in 5000 phenotypic females and the syndrome is able to show its presence in a number of ways. A number of physical abnormalities are associated with this syndrome for example, short stature, swelling, broad chest, low hairline, low set-ears and webbed necks. Females suffering from this disease generally undergo gonadal dysfunction resulting in amenorrhea and sterility.
Many health problems apart from the gonadal function are also associated with Turner syndrome for example, congenital heart disease, hypothyroidism, diabetes, visual impairment, hearing aids and risk of occurrence of autoimmune diseases. Last but not the least a specific pattern of cognitive impairment has been noticed in such individuals that includes problems in visuospatial, mathematical and memory areas. The name of the disease is given after its discoverer Henry H. Turner who was an endocrinologist from Illinois and identified this disorder in 1938. The disease is also known as Ullrich-Turner syndrome in Europe as the doctors have also identified the syndrome independently. Dr. Charles Ford and his coworkers at Harwell, Oxfordshire and Guy’s Hospital in 1959 published the report of a female with 45, X karyotype for the first time. A 14-year old girl was found to be suffering from this disease.
In general about 99% of all the fetuses suffering from Turner syndrome undergo spontaneous termination during the first trimester of pregnancy. This disorder accounts for 10% spontaneous abortions in the United States. The chance of occurrence of this syndrome is 1 in 2000 live females. Researchers have yet not identified which of the genes are present on X chromosome whose alteration result in Turner syndrome. Scientists have however, succeeded in identifying one gene known as SHOX that is responsible for growth and development. Loss or absence of one copy of this gene results in short stature and skeletal abnormalities in females with Turner syndrome.
The actual risk factors associated with this syndrome are yet not known. Genetic mosaicism, non-disjunction and partial monosomy are the major factors that can be regarded responsible for this syndrome. The chances of non-disjunction generally increase with the maternal age same as that found in the Down syndrome but the effect is not very clear in case of Turner syndrome. In about 75% cases the inactivated X chromosome is the parental origin of this disease. Many theories have been put forward to explain the exact reason responsible for this disorder and the strong one suggests that during conception either a part or whole of the second X chromosome is not transferred to the developing fetus that results in Turner syndrome. Such females lack Barr bodies.
The girls suffering from Turner syndrome are short in height than average. They have a normal height for the very first three years of their life and then the growth becomes slow. At puberty the growth rate experiences further declination. The ovaries of such females are non-functional and they are unable to produce the sex hormones. They also do not develop breasts and menstrual cycle also does not start unless and until they are treated with hormones at the age of puberty. Although in some females yet they are infertile but their vagina and womb function normally. In the early childhood girls suffering from this disease experience very frequent ear infections. Recurring ear infections can result in severe hearing aids. Girls have normal intelligence and are even good in verbal and reading skills. Some girls even experience difficulty in solving mathematical problems, memory skills and fine-finger movements. Additional symptoms of this disorder include widened neck with low hairline, broad chest and widely spaced nipples, arms move slightly at the elbows. A heart murmur due to narrowing of the aorta is often noticed. High blood pressure also develops minor visual problems also crop up that can be solved by wearing glasses. Hypothyroidism and osteoporosis also make their appearance in later stages.
The diagnosis of Turner syndrome can be made on the basis of a number of physical features like webbed neck, broad chest and widely spaced nipples. Sometimes diagnosis can be made at birth due to the presence of critical heart problems and unusual swelling of hands and neck. Price and coworkers in 1986 have clearly indicated that majority of deaths in case of this disorder are due to diseases of circulatory system particularly due to congenital heart defects and postductal coarctation of aorta. The chances of death due to cardiovascular disease in this disorder increases by three fold. The exact relationship between karyotype-phenotype characteristics that result in severe cardiovascular problems remains unclear till now. The chances of incidence of cardiovascular disease in individuals with this disease vary from 17-45%. Different karyotypes have shown different types of malformations associated with the cardiovascular disease. A study has indicated that the prevalence of cardiovascular disease is about 30-38% in individuals with pure 45 X, monosomy. Studies carried out with other karyotypes have shown that the risk of prevalence is about 23.4% and 11% in individuals with mosaic X monosomy and other X chromosomal structural abnormalities.
Congenital obstructive lesions of the left side of the heart are very commonly observed in Turner syndrome and this defect results in reduced blood flow in the left part of the heart. The congenital heart disease includes bicuspid aortic valve and coarctation of aorta. Sybert in 1998 have observed that 50% of the cardiovascular diseases that are associated with Turner syndrome are either due to bicuspid valve or coarctation of aorta in combination or alone. Other malformations include venous drainage and aortic regurgitation. Hypoplastic left heart syndrome is also observed in this disorder that results in severe damage of the left side structures of heart. About 15% of the individuals suffering from this disease have bicuspid aortic valves which mean that out of three only two valves are functional. As these valves are capable of maintaining normal blood flow this condition can only be detected if careful screening is done. Calcification also occurs later in these valves that results in progressive valvular dysfunction. The chances of occurrence of the bicuspid aortic valve defect in such individuals are about 12.5-17.5%.
About 5-10% of individuals with Turner syndrome suffer from coarctation of aorta which is actually descending of aorta just distal to the origin of the left subclavian artery and opposite to the duct also known as juxtaductal. The incidence of occurrence of this congenital heart disease varies from 6.9-12.5%. Karyotype test is recommended in such instances. Partial anomalous venous drainage is another relatively rare congenital heart defect found in individuals with Turner syndrome. While dealing with patients of Turner syndrome that suffer from such congenital heart disease special attention must be taken as these individuals are at risk of getting infected with bacterial endocarditis. Dental cleaning is recommended in such conditions. This disorder is often associated with persistent hypertension, sometimes in childhood also. The specific reason behind hypertension is not known.
Two studies have indicated that aortic dilation also makes its appearance in Turner syndrome. Allen and coworkers have carried out a study on 28 girls with this syndrome in 1986 and have reported that the mean aortic root diameter was greater in such girls. Another study carried out by Dawson-Falk and coworkers in 1992 reveals that mean aortic root diameter was greater in patients of this syndrome in comparison with the normal individuals. Sybert (1998) points out that this increased mean aortic root diameter increase the risk of progressive dilatation. The chances of occurrence of aortic root dilatation in individuals with Turner syndrome varies from 8.8-42%. Aortic root dilatation generally results in complications identified as dissection, aortic rupture and even death. Aortic dissection affects about 1-2% of individuals suffering from Turner syndrome. Routine surveillance is highly recommended in such situations.
It is well known that cardiovascular malformations and hypertension result in aortic dissection and dilatation in normal population and at the same time these defects are very common among individuals with Turner syndrome. Blood pressure of such individuals should be monitored regularly. It has been found out that individuals with the karyotype 45, X are at major risk of suffering from congenital heart diseases. The exact role of all these factors that crop up in fatal complications is still unclear. Pathological evidence has revealed that aortic root dilatation is due to mesenchymal defect. Similar findings have been found in the Marfan syndrome. Other mesenchymal defects have also been noticed in individuals with Turner syndrome.
Turner syndrome is characterized by primary amenorrhea, premature ovarian failure, streak gonads and infertility. However, with the advancement of technology the individuals with this disorder have an opportunity to conceive. Although the females can become pregnant but the risk of congenital heart disease in the developing fetus is at peak. The risk of aortic dissection in the fetus also increases in a pregnant female with Turner syndrome. Three deaths with this situation have been reported. Estrogen plays an important role but the exact function in such situations is unclear. It appears that the higher risk of aortic dissection in pregnant female with this syndrome is due to increased hemodynamic load rather than the increased estrogen rate.
The normal development of skeleton is also restricted in such individuals although a number of factors are responsible for this deformity but the major one is hormonal. The average height of a female with this disorder is about 140 cm in case when no hormonal treatment is applied. Patients suffering from Turner’s mosaicism may attain normal average heights. The fourth metacarpal bone is unusually short. Inadequate production of estrogen results in osteoporosis. The decreased height results in scoliosis in later stages. The risk of bone fractures also increases. Generally most of the females suffering from Turner syndrome suffer from three major abnormalities of the kidney. These embrace only a single horse-shoe shaped kidney on one side of the body, abnormal urine collecting system and poor blood flow to the kidneys. Some of these abnormalities can be cured with the help of surgery. Apart from these problems the kidneys in such individuals may function normally. These factors are generally associated with hypertension.
About one-third of the females suffering from Turner syndrome suffer from hypothyroidism particularly Hashimoto’s thyroiditis which can be treated with thyroid hormone supplements soon after diagnosis. Such females are also at risk of getting affected with type 1 diabetes in the early childhood and then with type 2 diabetes in the adulthood. The risk of developing type 2 diabetes can be prevented by the maintenance of normal weight. This syndrome generally does not result in mental impairment but nonverbal learning disorder is very frequent in such individuals. A very rare type of Turner syndrome known as Ring-X Turner syndrome is also found that results in 60% cognitive impairment. The incidence of this rare type of disorder is 2-4% in individuals suffering from Turner syndrome.
The females with this syndrome are almost infertile but some females especially those with the karyotype 45, XO can become pregnant. However, when such females conceive then the risk of miscarriage and chances of birth defects particularly Turner syndrome or Down syndrome in the child are at maximum risk. The females who are unable to conceive due to this disorder can be made to conceive by in-vitro fertilization (IVF) or by hormonal treatments. Estrogen replacement therapy is generally used for the development of secondary sexual characteristics. Very few females with this disorder menstruate regularly however, estrogen replacement therapy requires regular shedding of the uterine lining to in order to prevent its overgrowth. Withdrawal bleeding in such females can be induced in every three months if the patients are willing for it. This therapy does not make a female with nonfunctional ovaries fertile but it plays an important role in reproduction.
Turner syndrome can be detected during the pregnancy by ultrasound test. Chorionic villus sampling or amniocentesis is other techniques for its detection. After its confirmation the baby is treated soon after its birth. Diagnosis can be done by a blood test identified as karyotype. This test is used for the identification of chromosomal composition. During childhood and adolescence the girls must be taken to the pediatric endocrinologist who diagnoses the condition of hormones and their metabolism. Growth hormone injections are also beneficial as they help in attaining average height. Estrogen replacement therapy must be started at the age of 12 for the development of secondary sexual characteristics as well as for preventing osteoporosis. Help of cardiologist must be taken if the babies are identified with congenital heart problems. As the females with Turner syndrome are at risk of getting infected with middle ear infection so a regular help of ear, nose and throat specialist (ENT) must be taken. High blood pressure is another problem very common in such females so blood pressure must be checked regularly. Regular health checkups are very important in these individuals. The females can become pregnant but for that donor embryos are required. Proper and regular health checkups help such females to enjoy life normally.
Turner syndrome is generally not inherited in the families it occurs when one of the two X chromosomes in a normal female are missing or incomplete. The exact cause of this disorder is generally not known but it is believed that the disorder is due to a random error that occurs at the time of egg or sperm formation. Humans have 46 chromosomes that contain all the genes and DNA. Out these 46, two chromosomes are responsible for the identification of gender. Females have two X chromosomes while males have one X and one Y chromosomes. These two chromosomes help an individual to develop the characteristics specific for their gender. In females with this disorder usual two chromosomes are not found and in general they have one X chromosome. In some females incomplete X chromosome is present or both the X chromosomes are absent.
Love, care and family support coupled with proper treatment can help the females with Turner syndrome to live their lives joyfully. Researches are working tirelessly to reveal the hidden secrets of this syndrome so that the future generation may not suffer from problems.