One evening, over drinks in a local pub, a close friend asked me how TS affects me and to my astonishment, I found it difficult to give a clear and concise response. First, there is the fact that I look about half my age, stemming from a combination of both my short stature and, I hope, good genetics. This has enormous social implications. To this day, I still get mistaken for someone who is under Only two years ago, I was at a Turner Syndrome conference in a Manchester hotel.
Needless to say, bar staff and management received a serious education on Turners Syndrome that night. Over the years, people have treated me differently as well because they believed I was much younger than my years.
Second on the list of concerns is the matter of infertility. In TS women, the ovaries do not develop, meaning absolute certain infertility. I consider myself fortunate on this front as my maternal instincts have never reached stratospheric heights anyway. I have never really harboured any great desire to have children of my own, never had this grand plan.
From an early age, my parents raised me with the knowledge that I would never have children of my own and so I have never known any different.
I realise that this may become problematic if I ever do meet a partner and he desires children but, for now, I have accepted my fate. In the last few years, some friends of mine have had children of their own and, of course, it does hit me like a tidal wave from time to time that this is a life I will never lead, but I have learned to make my peace with that.
There are alternative options available to me in the form of IVF and adoption but both are emotionally draining, costly and lengthy processes. To add to that, pregnancy carries serious risk of medical complications, in particular high blood pressure and TS women are in fact advised to avoid this option, and is therefore not an avenue I would ever wish to explore. Of all the trials and tribulations that come with a life living with TS, personally, I have found my social inadequacies the most difficult to accept.
TS women suffer from crippling self-esteem issues largely arising from short stature and a feminine inferiority. This has a profound impact on social skills and ability to make and maintain new friends. Couple that with significant hearing impairment, a lack of spontaneity and a short attention span — all elements of the syndrome. Making conversation, engaging with people in a really meaningful way is something I find extremely difficult.
One of the most notable social inadequacies in TS women is a distinct inability to read and interpret a situation, stemming from poor observation. Socially, this comes with many disadvantages. I know I personally have completely misinterpreted a situation or completely misinterpreted something someone said on countless occasions. And unfortunately that does lead to some inevitable hairy moments.
It makes simple everyday tasks particularly challenging. These might all be characteristic of your average person, but they are certainly more pronounced in TS women. They were forced to learn to cope on their own. A family perspective on TS is essential. After leaving school, I studied General Nursing in Cork and I was convinced it was the career for me.
I made some lifelong friends throughout this programme and I spent four happy years working hard pursuing a career I loved. Unfortunately life intervened: I fell down on the clinical practice element of the programme on issues such as problem solving, critical analysis and thinking on the spot. Common problems for people with TS. Open journalism No news is bad news Support The Journal Your contributions will help us continue to deliver the stories that are important to you.
After repeating the clinical practice component of the final year, it was time to hang up my nursing dreams. This was by far the lowest point in my life. Had it not affected me enough with all the medical complications, the lack of friends, the lack of feeling normal?
I was sick of it seeping into every aspect of my life — socially, medically, academically, practically. I vividly remember breaking down one morning shortly afterwards while attending mass with my parents. It was like I was only fully processing everything that had happened to me over the past few months that morning, with that song.
Everything hit me at once. How had I ended up in this mess? How had my life fallen to pieces so fast? As a child I was always the studious one, I had always imagined myself following a blossoming career, not sitting idle at 24 wondering what I was going to do with the rest of my life!
It was only afterwards I learned that many TS women pursued a career in nursing but fell short on the clinical front. Spurned on by this knowledge, I felt compelled to help other TS women and prepare them for the exceptionally difficult transition into adulthood.
Currently, I am working towards establishing a friendship group here in Ireland, where TS women can get together, develop strong friendships and share their experiences. Many TS women feel so alone in their fight against their short-comings, often all it takes is to meet with others in a similar position to counteract those feelings of isolation.
I am also highly passionate about the need for education; there exists a large cohort of girls going undiagnosed until 12 or 13 years of age, only receiving a diagnosis with the absence of puberty. All potential to gain maximum adult height is lost with a diagnosis as late as this and doubles the difficulties experienced by the TS sufferer. I personally experienced a significant cutback in the level of care when I transferred from paediatric to adult specialists.
I believe this is an ironic twist of fate as the transition into adulthood is when the greatest need for care arises. While adult medical services are based on a different ethos and premise compared to paediatrics, I found adult doctors woefully lacking in specific knowledge on TS-related health issues.
To think that even in the medical field TS is a little known condition gives me cause for great concern and I eventually hope to make a difference.
As with any medical condition or situation in life support is invaluable — it is central to survival. One of the most beautiful things to come out of hardship is that, to survive, you must look deep within yourself and find who you really are. It challenges you to examine yourself in a way that only hardship can and I certainly found a certain sense of empowerment arose out of this. Instead of looking at what was wrong with my life, I challenged myself with the glass-half-full motto.
I was surrounded by amazing family and friends; I was afforded the opportunity to do an extra essay which would allow me to achieve a level 8 honours degree. In turn, I could then look forward to postgraduate study in a topic of my choice. And that is exactly what I did! GH treatment for at least 1 yr improves bone mineral density 58 , 60 , 61 , although the bone mass remained below the normal value for age.
Early estrogen therapy has also been shown to improve, but not normalize, bone density 52 , Mora and colleagues 62 found that girls who had started sex steroids before the age of 12 yr had a higher bone mass than those who started treatment after the age of 12 yr. The combination of estrogen replacement therapy and GH treatment results in a greater gain in bone mass 60 , In girls with TS who enter puberty spontaneously, bone mass has been found to be within normal limits After adolescence, estrogen replacement therapy seems to be the single most important factor in maintaining peak bone mass.
Sylven and colleagues 57 looked at bone mineral density in 47 middle-aged women with TS and found that women with TS had a bone mass less than age-matched normal values. They also found that the duration of hormone replacement therapy HRT was the significant factor in maintaining bone mass. Finally, Davies et al. Since bone mass is improved but not normalized after hormonal therapy 65 , an intrinsic bone defect is likely. The cause of osteopenia in TS is probably a result of the combination of an intrinsic bone defect in addition to estrogen deficiency.
However, if this were the case, one would expect bone density to be higher in women with a mosaic karyotype compared with 45,X monosomy, but there are no data correlating bone density in TS with karyotype 52 , 53 , 56 , Further research is required to determine whether loss of genes on the X chromosome may predispose women with TS to osteopenia.
Additionally, further longitudinal studies are required to assess the prevalence of clinically significant osteoporosis and osteoporotic fractures in TS. Estrogen replacement should be optimized and lifestyle advice given with regards to exercise and adequate calcium intake. Weight-bearing exercise has been shown to improve bone mass in women with TS All women with TS should have a bone densitometry performed on transfer to an adult clinic, and bone mass should then be monitored, although the frequency of monitoring remains controversial.
The role of bisphosphonates in the treatment of osteoporosis in women with TS has yet to be clarified. Lymphedema, the result of obstruction at the level of the lymphatojugular connection, is a major defect in TS, which is present in affected fetuses, particularly those with 45,X monosomy. When severe, this results in fetal wastage as a consequence of severe generalized lymphedema, but spontaneous resolution can occur with subsequent live birth.
Milder lymphedema is responsible for some of the typical features of TS, such as a webbed neck, ptosis, and a low posterior hairline. Lymphedema of the hands and feet may be present at birth but often resolves.
It may recur, particularly after the initiation of estrogen therapy. Nail dysplasia pitting nails and lateral hyperconvexity pathognomonic of TS is also thought to be secondary to lymphedema. Fetal lymphedema may also be responsible for the development of aortic coarctation see Section VII. In a karyotypically normal fetus, the number of germ cells rises progressively to , by 2 months post conception to a maximum of 7,, at about 5 months gestation.
There is then a progressive germ cell degeneration up until the age of menopause The gonads in TS differentiate normally until the third month of gestation.
After this period, the absence of part, or the whole, X chromosome in the germ cells results in an accelerated degeneration of oocytes and an increase in ovarian stromal fibrosis Ovarian failure occurs within the first few months or years of life. Ultrasonic assessment of the pelvis in females with TS reveal the majority to have streak ovaries and, in many, the ovaries are too small to be identified In females with TS who have not had estrogen treatment, the uterus is hypoplastic and remains prepubertal in size.
Most females with TS do not enter puberty spontaneously because of the early gonadal failure and subsequent estrogen deficiency. Spontaneous breast development is either minimal or does not occur, and primary amenorrhea is usual. However, few women with TS will maintain ovarian function with resultant fertility. Additionally, the outcome of these pregnancies is often poor Table 3. However, it may be that these figures are affected by publication bias and that prospective monitoring of adult cohorts could reveal a more favorable spontaneous pregnancy outcome.
Data taken from the following references: Refs. The majority of women with TS require long-term estrogen replacement therapy. After the induction of puberty and the completion of growth, females with TS should be maintained on cyclical estrogen-progestagen therapy. Estrogen replacement therapy in adults with TS is important in the prevention of osteoporosis 57 and in reducing risk factors for atherosclerosis , In addition, it has been shown recently that estrogen replacement may improve aspects of cognitive function in women with TS The role of estrogens in the protection against colonic cancer remains tentative, but studies have shown that rates of colon cancer can be halved in postmenopausal women by estrogen replacement therapy , This protection is extremely relevant in females with TS, as they have been shown to have an increased risk of colorectal neoplasms 59 , The estrogen dose and route of administration should be individualized taking into account patient preference and coexisting illness Table 4.
The oral route is the most popular, but transdermal estrogen patches avoid first-pass hepatic metabolism and are therefore ideal in women with liver disease or hypertriglyceridemia.
Natural estrogen preparations such as conjugated estrogens or E2 valerate have a benefit over oral contraceptive preparations in that they nearly all offer continuous estrogen for 28 d without a pill-free week.
A proportion of women with TS using the oral contraceptive will be symptomatic of estrogen in the pill-free week. In addition, the presence of ethinyl E2 in the oral contraceptive pill has been associated with an increased incidence of liver disease in women with normal karyotypes as well as in women with TS It may also have an adverse effect on lipid metabolism through its effect on hepatic metabolism, and it may exacerbate hypertension, a common problem in TS.
Alternatively, a continuous combined regimen, with the advantage of no menstrual bleeding after the first year of therapy, might be considered, although the long-term outcome of its use in young women is lacking. The risk of breast cancer in women with TS is not thought to be higher than in the general population 59 , , and the use of physiological doses of estrogens should not contribute to an excess risk.
The duration of HRT after the age of 50 yr should be made on an individual basis, weighing the risks and benefits for each woman. Chromosomal and congenital abnormalities are present in almost half of surviving babies.
Fertile women with TS should therefore be counseled with regard to these increased risks and be offered prenatal diagnostic testing. Moreover, they should be advised to consider the high risk of early ovarian failure when planning pregnancies. The majority of women with TS, however, will be infertile. Pregnancy may be achieved by oocyte donation and in vitro fertilization.
Oocyte donation has been available over the past 15 yr to treat women with premature ovarian failure of any cause Best results are achieved once the endometrial thickness is greater than 6. This is thought to be due to uterine hypoplasia in TS and possibly relative uterine ischemia during pregnancy Most women with TS require cesarean section for delivery because of cephalopelvic disproportion resulting from their body habitus.
Women with TS who do become pregnant may be at increased risk from cardiovascular complications, particularly aortic root dissection Section VII. At least three deaths have been reported in pregnant women with TS from aortic dissection , All women should therefore undergo a full cardiological assessment before seeking to become pregnant, including echocardiography or magnetic resonance imaging MRI of the aortic root, cardiac valves, and left ventricular function.
Hypertension is more common in young women with TS, and this should be monitored and treated aggressively. However, preeclampsia does not seem to occur with increased frequency in TS. There is currently much research into the removal of functioning ovarian tissue followed by its cryopreservation with the aim of reimplantation at a later stage when fertility is required , Its clinical application has centered mainly on women who are scheduled to begin cancer chemotherapy; however, it may also be suitable for the few women with TS who exhibit early evidence of ovarian function but are at high risk of later ovarian failure.
Research into this technique is still in its infancy. There have been no cases to date of successful human ovarian autotransplantation. If this technique is considered, subjects and their families must be counseled about the uncertainty of future success rates associated with this ovarian cryopreservation.
The optimum age for ovarian biopsy in females with TS with normal gonadotropins is unknown and should be individualized, possibly based on serum inihibin levels, a more sensitive indicator of ovarian function. However, it is likely that ovarian cryopreservation should be considered in childhood or early adolescence. Furthermore, because of the high risk of fetal abnormalities associated with spontaneous pregnancies in females with TS, donor oocyte donation may be more appropriate.
The increased mortality in TS is primarily a result of its cardiovascular complications 8 , 9. It has long been known that left-sided congenital cardiac abnormalities are more prevalent in women with TS, but recently, other cardiovascular risk factors have come to light, particularly the increased risk of aortic dissection and ischemic heart disease.
These studies also indicate that structural cardiac anomalies are most prevalent in women with pure 45,X monosomy and tend to be less common in those with an isochromosome Xq karyotype.
Bicuspid aortic valve is the most common congenital malformation affecting the heart — It is usually an isolated abnormality. However, it may occur in combination with other anomalies, particularly aortic coarctation, and, as it calcifies, may result in progressive valvular dysfunction, as evidenced by aortic stenosis or regurgitation. The cause of the abnormal aortic valve is unknown. It is particularly common in females with webbing of the neck 5 , This association, in addition to the high incidence of aortic coarctation in 45,X aborted fetuses with severe lymphedema , has led to the theory that aortic coarctation is a result of the abnormal lymphatic flow in TS altering intracardiac blood flow by compressing the ascending aorta 5 , , Aortic coarctation, providing it is the only cardiac abnormality, is usually surgically corrected in childhood with excellent results.
Untreated, it may be complicated by aortic rupture, congestive cardiac failure, and persistent hypertension. Seirafi and colleagues , who studied the outcome of surgery in patients with aortic coarctation, found that surgical repair before the first year of life was less likely to be associated with persistent hypertension 4.
Other cardiac anomalies, such as partial anomalous venous drainage and mitral valve prolapse, are also more common in TS compared with the general population — All left-sided cardiac anomalies associated with TS result in an increased susceptibility to infective endocarditis, and therefore prophylactic antibiotics before dental or surgical procedures are essential.
Patients with cardiovascular anomalies require long-term cardiological follow-up. In the last decade the association of aortic dissection and TS has been increasingly recognized Table 6 , with several reports of sudden death. As with other structural cardiac anomalies, it is most commonly associated with 45,X karyotype. Elsheikh et al. Aortic dilatation or dissection may occur at any age, and in the published literature just under half the patients were diagnosed before the age of 21 yr Aortic root dilatation is thought to be due to a mesenchymal defect , as pathological evidence of cystic medial necrosis has been found by several investigators.
Additional research is needed to determine whether an abnormality of the X chromosome may affect collagen synthesis and be responsible for the connective tissue abnormalities seen in TS. The influence of estrogens on the natural history of aortic dilatation is unknown. Aortic root dilatation often develops before the administration of exogenous estrogens, and there have been no reports to suggest any deterioration after HRT.
However, pregnancy certainly increases the risk of progression to aortic dissection , , , although this may be due to the increased hemodynamic load rather than the high estrogen state. Echocardiography is the mainstay of diagnosis of aortic dilatation; however, studies have shown that magnetic resonance imaging MRI can detect dilatation missed on echocardiography MRI should be used if aortic root dilatation is detected to examine the severity and provide more precise measurements relevant to follow-up.
The current difficulty in the interpretation of images is the lack of normal values for aortic dimensions relevant to females with TS.
The normal aortic root diameter correlates with height; therefore, use of the normal range for karyotypically normal women may produce falsely reassuring results.
To obviate this problem, normal ranges based on age and body surface area should be used , Alternatively, some investigators suggest using a ratio between the aortic root diameter and descending aorta A ratio of greater than 1. Their efficacy in females with TS has not been examined. It is essential, however, that hypertension is treated aggressively and that elective surgical intervention should be considered for patients with critical or progressive dilatation. Until more is known about the natural history of aortic root dilatation, it is currently recommended that females with normal echocardiograms are imaged every 5 yr and those with abnormal echocardiograms are followed up annually by a cardiologist MRI of the aorta in a woman with TS showing a dilated aortic root highlighted with paired arrows.
The ratio of diameter of the aortic root a to the descending aorta b is greater than 1. The risk of hypertension is increased 3-fold in women with TS Furthermore, even girls with TS who are normotensive have been shown to have an abnormal circadian blood pressure rhythm, with loss of nocturnal reduction in blood pressure, increasing the risk of end-organ hypertensive damage , Failure to recognize hypertension may contribute to the excess cardiovascular mortality in women with TS.
Thus, the majority of women have no obvious secondary cause for hypertension despite the young age of onset. There does not appear to be an association with karyotype, and it is hypothesized that hypertension is secondary to small vessel renovascular disease 5 , as elevated renin activity has been shown in hypertensive girls with TS before estrogen therapy is initiated The use of ethinyl E2 as estrogen replacement therapy may exacerbate hypertension, but the use of natural estrogens and GH therapy does not seem to influence blood pressure , , The incidence of ischemic heart disease in adults with TS is unknown, but a recent epidemiological study from Denmark 59 indicates that women with TS may be twice as likely to develop coronary artery disease compared with the general population.
Women with TS have several risk factors for ischemic heart disease and atherosclerosis that include, in addition to hypertension, insulin resistance and hyperlipidemia.
Type 2 diabetes mellitus DM is 2—4 times more common in women with TS compared with the general population 59 , and tends to develop at a younger age. Karyotype does not seem to influence glucose tolerance. Cicognani et al. Caprio and colleagues have demonstrated an early metabolic defect in glucose uptake resulting in reduced insulin sensitivity and hyperinsulinemia, and this may explain the high incidence of carbohydrate intolerance in TS. They also showed that this was independent of body mass index, although obesity, a common problem in TS , — , will aggravate the insulin resistance.
The cause of obesity in females with TS is unknown, but may be related, in part, to estrogen deficiency. Certainly the introduction of HRT improves fat-free mass and waist-hip ratio in women with TS without affecting body mass index , Gravholt and colleagues also showed that women with TS had reduced physical fitness as evidenced by a reduction in maximal oxygen uptake, which is only partially improved by sex hormone replacement.
Further research into the pathogenesis of obesity in females with TS is warranted. Hyperinsulinemia may be present in childhood, before hormone treatment. GH therapy has been shown to further aggravate hyperinsulinemia , , , but not glucose intolerance, as the effects are reversed 6—12 months after therapy is discontinued.
Whether sex hormone replacement therapy aggravates glucose intolerance in women with TS remains unclear. Gravholt and colleagues demonstrated a deterioration in glucose tolerance as assessed by an oral glucose tolerance test after 6 months of estrogen therapy, with an impaired insulin response.
In contrast, we have demonstrated an improvement in insulin sensitivity in women with TS by the administration of HRT , which is consistent with several randomized studies in karyotypically normal postmenopausal women, showing a reduction in insulin levels with HRT , Gravholt and colleagues 59 also showed an fold increase in the frequency of type 1 DM in their study population. This may, however, be due to misclassification of insulin requiring type 2 DM, as this has not been the experience of other groups 5 , Additionally, islet cell antibodies are not present to excess in females with TS , Hypercholesterolemia has been demonstrated in Turner girls as young as 11 yr and does not seem to be influenced by karyotype.
Ross and colleagues studied girls with TS, all under 14 yr of age, and showed that girls above the age of 11 yr had significantly higher total, high-density lipoprotein, and low-density lipoprotein cholesterols compared with karyotypically normal controls, irrespective of body mass index. However, other investigators have not confirmed that cholesterol values differ from those of karyotypically normal women , , , Hypertriglyceridemia occurs with increased frequency in TS and may be a direct consequence of obesity and hyperinsulinemia GH therapy has been shown to reduce total and low-density lipoprotein cholesterol and increase high-density lipoprotein cholesterol in adolescent girls with TS , although it is unlikely that this effect is sustained once treatment is discontinued.
Short-term studies looking at the effect of estrogen replacement therapy on metabolic parameters in TS have failed to show an effect on lipids , , HRT has been shown to have a favorable effect on cholesterol concentrations in postmenopausal women , , and it may be that longer term trials are required to definitively assess the effect of HRT on lipids in females with TS. Premature ovarian failure of any cause has been demonstrated to increase cardiovascular mortality , and the use of HRT in postmenopausal women is likely to reduce the risk of ischemic heart disease , Women with TS should therefore have an annual cardiovascular evaluation.
Endocarditis prophylaxis should be given to those with known cardiac anomalies. All adults with TS should have at least annual blood pressure measurements. However, more than one drug may be required to control blood pressure. Women with TS should have an annual fasting blood glucose and lipid profile, and weight loss in obese patients should be encouraged. The effect of aggressive lipid lowering on the risk of ischemic heart disease in women with TS has not been studied.
Estrogen replacement should be individualized. Those women with no cardiovascular anomalies diagnosed in childhood should be echoed regularly to monitor aortic root diameter. It is still unclear as to how often this should be done, but the current recommendation is every 5 yr. If there is any doubt, MRI may be a useful adjunct in assessing aortic dilatation. Those women with a known cardiovascular anomaly should be followed up by a cardiologist.
Radetti et al. The incidence of autoimmune thyroid disease in females with TS increases with age. Chiovato and colleagues demonstrated a doubling in the prevalence of autoimmune thyroid disease from the first to the third decade of life.
There does not seem to be an increased frequency of positive thyroid autoantibodies or of hypothyroidism before the age of 10 yr — Germain and Plotnick demonstrated a peak incidence of thyroid dysfunction at the age of 15 yr and that the ability of positive thyroid autoantibodies to predict the development of thyroid dysfunction increases from the age of 13 yr.
This is perhaps surprising considering the similar pathogenetic mechanisms of autoimmune hypo- and hyperthyroidism. Autoimmune thyroid disease has been found to be particularly prevalent in women with the isochromosome [46,Xi Xq ] karyotype compared with other karyotypes , Other autoimmune diseases are also associated with the isochromosome X, suggesting that an abnormality of the X chromosome may be linked with autoimmunity.
The exact pathogenesis of thyroid and other autoimmune diseases in TS is unknown. The effect of GH therapy on the occurrence of positive thyroid autoantibodies has been studied by two groups with conflicting results. Nienhuis and associates suggested that GH therapy increased the risk of developing thyroid autoantibodies but not the risk of developing clinical disease.
However, this has been refuted by Ivarsson and colleagues , who found an increased prevalence of thyroid autoimmunity in 89 girls with TS compared with controls, but the prevalence did not rise after up to 5 yr of GH therapy.
It may be that the rise seen in thyroid autoantibodies in the first study was related to the increase in autoimmune thyroid disease with age, but further data are required.
We suggest that all females with TS should have thyroid autoantibodies and TSH checked annually beginning at the age of 10 yr. If the thyroid autoantibodies become positive, then repeat measurements are not required and the patient should be followed up with an annual TSH measurement. Hypothyroidism should be treated promptly to avoid associated morbidity, particularly obesity and hyper- cholesterolemia. Congenital renal anomalies are approximately 9 times more common in females with TS compared with the general population Renal abnormalities Table 8 occur through a number of mechanisms: an early defect in ureteric budding may give rise to a double collecting system or absent kidney, and an abnormality in migration of the kidney from the pelvis may result in a pelvic or a horseshoe kidney.
These abnormalities do not usually result in significant morbidity. However, the risk of pyelonephritis and pelvoureteric obstruction is increased, thus increasing the risk of chronic renal impairment.
Surgical intervention was required in 4 of the 49 girls 8. The frequency of renal malformations is higher in females with 45,X monosomy but the association is weak and renal disease may occur with any karyotype , Renovascular abnormalities are also more prevalent in TS and may be at least partially responsible for the increased incidence of hypertension in TS.
All females with TS should therefore have a renal ultrasound performed at the time of diagnosis. If significant abnormalities are detected, appropriate evaluation and therapy should be instituted. Urinary tract infections should be treated vigorously and renal obstruction relieved. Subsequent monitoring for progressive renal impairment, either as a consequence of obstructive uropathy or recurrent infections, and hypertension is essential.
However, other studies found the risk to be even greater. We looked at the prevalence of IBD in women with TS whose medical details are held on the adult Turner register database and found a similar prevalence of IBD of 2. The reason for this is unclear. Gastrointestinal symptoms often develop at a young age, the median age of onset being 16 yr range 9—40 yr.
Inflammatory bowel disease is often severe in women with TS and has been fatal in at least three cases. Death from IBD. IBD, like most immune-mediated diseases, is more common in women. Additionally, the increased risk of IBD in TS, particularly in the presence of an X isochromosome, would suggest that perhaps a gene on the long arm of the X chromosome Xq may be associated with immune dysfunction. There have been several reports suggesting that women with TS are also at increased risk of gastrointestinal bleeding from intestinal telangiectasia 5 , , This is thought to be a developmental defect, but does not seem to be associated with vascular malformations elsewhere.
An iron deficiency anemia is a common presentation, in addition to intermittent gastrointestinal hemorrhage. Fortunately, severe hemorrhage is rare and most cases respond to conservative management. There have been reports of celiac disease developing in women with TS , , , but it is unlikely that it occurs with an increased frequency.
Recent evidence suggests that women with TS have an increased risk of developing chronic liver disease. Gravholt and colleagues 59 have shown the prevalence of liver cirrhosis in TS to be 5 times that of the general population.
There have been several cases reported in the literature associating TS with portal hypertension and either hepatic cirrhosis or fibrosis — We looked at liver function tests in our clinic population The cause of abnormal liver function in TS is unclear, but it does not seem to be related to alcohol excess or infectious hepatitis.
We did not show a correlation between abnormal liver function and karyotype, body mass index, or type or duration of HRT It remains unclear as to whether the abnormal liver function is related to an autoimmune process, and the risk of progression to hepatic cirrhosis is unknown. Liver biopsies have revealed a variety of abnormalities ranging from fatty infiltration to hepatic fibrosis and vascular abnormalities.
Some authors found liver morphology in women with TS to resemble that of a newborn liver and thus hypothesize that hepatic abnormalities in TS may be due to failure of normal development as a result of lifelong estrogen deficiency , We noted a significant improvement in liver function after E2 valerate therapy However, this has not been the experience of other investigators. Wemme and colleagues showed a rise of serum liver enzyme concentrations after therapy with conjugated estrogens, and Masters noted a similar deterioration in liver function in women taking ethinyl E2 Certainly, the use of the combined oral contraceptive pill has been associated with an increased incidence of liver disease but the use of natural estrogens such as E2 valerate has not been shown to adversely affect liver function , in women with normal karyotypes and hepatic function.
In TS, however, the effect of estrogens on liver function remains controversial. Until this issue is resolved, transdermal estrogens are recommended in those women with elevated liver enzymes, as these have less deleterious effects on hepatic metabolism The incidence of breast, ovarian, and endometrial cancers does not seem to differ from that of the general population 57 , There have been some case reports linking TS with endometrial carcinoma — ; however, these were associated with unopposed estrogen therapy.
The risk of developing breast or endometrial cancer may increase with the increasing use of sex HRT in women with TS. HRT has obvious benefits to women with TS, which far outweigh the risks, but to reduce the risk of breast or endometrial cancer it is very important that natural estrogens are prescribed in physiological doses and in combination with a progestin. Gonadoblastomas vary widely in size, but the larger tumors are more likely to harbor a malignancy They may produce androgens or estrogens, resulting in virilization or feminization, respectively.
Early prophylactic excision of the gonads is thus recommended in all Turner mosaics with Y chromosome material detected on routine karyotyping. The exact pathogenesis of gonadoblastoma is unknown. The sharp rise in its incidence after puberty suggests that sex hormones may play a facilitative role in the development of these tumors. Certainly, gonadectomy should ideally be performed before estrogen replacement therapy. Gravholt and colleagues 59 found that women with TS are 5 times more likely to develop cancer of the colon.
This is in keeping with an earlier report by Hasle et al. However, there has been a paucity of reports of colonic neoplasia in association with TS in the literature , It therefore remains unclear as to whether the association between colonic malignancy and TS is coincidental or whether a real association exists. Although women with TS are at increased risk of IBD, which itself predisposes to colon cancer, IBD did not precede the development of colon cancer in any of the reported cases.
The underlying mechanism for an increased risk of carcinoma is therefore speculative. Longstanding estrogen deficiency may play a role in the pathogenesis of colon cancer as ERs are normally found on the colonic mucosa, and epidemiological studies in postmenopausal women suggest that HRT reduces the risk of cancer of the colon , There have been a few cases reported in the literature of females with TS developing leukemia — However, the incidence of leukemia does not seem to be higher in females with TS.
Women with TS do not seem to be at increased risk of developing other malignancies. The congenital craniofacial malformations and consequent distortion of the eustachian tubes and impaired ventilation of the middle ear predispose girls with TS to middle ear infections. There was a relationship with karyotype: ear problems were least prevalent in women with mosaicism. Similar findings were demonstrated by other investigators , Conductive hearing loss consequent to recurrent otitis media is thus a problem in a significant proportion of women.
This was again least frequent in girls with mosaicism. Hultcrantz, Sylven, and colleagues , showed a similar abnormality in adults with TS. The cause of sensorineural deafness is unknown, but it is postulated that it may be due to a premature ageing process.
Hearing loss due to both sensorineural and conductive deafness appears to be most severe in subjects who lack a short arm of an X chromosome, such as women with 45,X monosomy or isochromosome X, compared with those with mosaicism or partial deletions of Xp , Regular audiological evaluation should therefore be routine in view of the high risk of both sensorineural and conductive hearing loss, as deafness can be quite profound before the symptom is volunteered.
Strabismus is the most common abnormality, present in one third of women , Other defects that occur with increased frequency in TS include amblyopia and reduced color vision. These abnormalities, thought to occur as a result of fetal lymphedema, often require surgical correction.
GH therapy may cause a reversible increase in naevi growth , but the clinical significance of this is unclear. The etiology of naevi in TS is unclear but may be related to a neural cell crest defect. In contrast to pigmented naevi developing in karyotypically normal women, sun exposure is not a major determinant of naevi growth in TS There have been two reports of malignant melanoma developing in women with TS , , but the risk of malignant transformation of melanocytic naevi is not increased in TS Naevi should therefore be removed only if they are located in an area where they are likely to be rubbed by clothing or if malignant transformation is suspected.
Immune-related dermatological conditions such as psoriasis, alopecia, and vitiligo also occur with slightly increased frequency in TS. The prevalence of psoriasis in females with TS is twice that of the general population.
Additionally, alopecia areata is 3 times more common in women with TS 5 , No obvious correlation with karyotype has been noted, but the number of reported cases is small. Long-standing estrogen deficiency may result in fine facial wrinkling in untreated women with TS. Finally, women with TS are at increased risk of developing keloid scars after surgery, although the evidence remains anecdotal. They should therefore be counseled about the risk of keloid scars before surgery.
There have been several reports in the literature suggesting that it occurs with greater frequency in females with TS 90 , — The onset of symptoms often coincides with the onset of estrogen therapy — No correlation with karyotype has been observed. Females with TS have, in general, normal intelligence, the exception being in females with a mosaic karyotype that includes a small ring X chromosome.
Migeon and colleagues demonstrated the absence or an abnormality of the X-chromosome inactivation center in tiny ring X chromosomes in females with TS and severe intellectual impairment. Van Dyke et al. Zenger Hain and associates showed that in females with a similar karyotype, but in whom the r X chromosome was inactivated, intelligence was normal.
These results have also been demonstrated by other investigators , A significant number of females with TS have deficits in specific areas of intellectual performance. They usually have normal verbal abilities but impaired nonverbal skills such as visual-spatial processing , , motor coordination — , and perceptual abilities This may be reflected by poor arithmetic skills, difficulty with constructional tasks, poor sense of direction, and difficulty in learning to drive.
They may also have a reduction in short-term memory and attention span , Additionally, executive function the ability to plan and execute multistep tasks may be impaired in some women with TS , Create a plan for transitioning into adult care. There are treatment options to improve quality of life and treat complex health issues.
Learn what you need to know to manage your health. Understand Turner Syndrome throughout all stages of life. A well-informed caregiver will find what they need to know to advocate for their child to ensure the best possible future. Information for expectant parents, parents of newborns, early childhood, adolescents and transition to adult care is available.
Life Cycle. Coming to terms with a recent diagnosis is a different process for everyone. There is neither a right or wrong way of when you decide to share the information or who you share the information with. Always remember that TS does not define a person. Learn More. Establishing good relationships and ensuring the best possible care for your child starts with open communication.
Have confidence and use your communication skills to self-advocate. The impact of TS can create various cognitive issues, as well as social issues, for all different ages.
Our map is a user-friendly, growing resource that lists specialized centers of care in the United States. Use this tool to find care near you and submit the doctors you or your child see so it can be added to our list of resources. Mapped Resources. Discover answers to your frequently asked questions about TS. Independent living, traveling, off to college or camp, these are times when you must think of safety on the go. Workforce development is a government lead program to assist with helping people get back to work.
They are regionally located and will provide mentoring and training to assist with resume, interview skills and placement.
0コメント