Growth rates and the prevalence and progression of scoliosis in short-statured children on Australian growth hormone treatment programmes

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808441/figure/F2/

This is an Open Access article distributed under the terms of the Creative Commons Attribution License

User:Z3060621

2011-10-13T01:03:14Z

Z3060621: /* LAB ATTENDANCE */

Z3060621: /* Introduction */

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== Turner Syndrome ==

--[[User:S8600021|Mark Hill]] 10:44, 8 September 2011 (EST) Some of the existing sub-sections have appropriate content, but there are also empty sub-sections, a total lack of referencing/citation and no glossary.
* The referencing issue needs urgent progress.
* Existing figures/table are appropriate. Table appears to be directly used from an uncited source.
* There needs to be more images in this work.
* Where is the student drawn figure?
* Read http://embryology.med.unsw.edu.au/embryology/index.php?title=Help:Reference_Tutorial#Multiple%20Instances%20on%20Page

== Introduction ==

Turner Syndrome (TS), named after Henry Hubert Turner who first described the syndrome in his paper in 1938,<ref><pubmed>4557013</pubmed></ref> is one of the most commonly occuring chromosomal disorders. It is caused by a complete or partial X [[#Glossary19 | '''monosomy''']] in some or all cells and occurs in approximately 1 in 2000 live female births, however the morbidity rate of spontaneous abortions is 10% and only about 1% of fetuses survive to term.

During normal fetal development, each ovary contain as many as 7 million oocytes. The oocytes gradually reduce to 400,000 during menarche and during menopause fewer than 10,000 remains. However, in Turner syndrome, the ovaries develop normally during embryogenesis but the absence of the second X chromosome leads to an accelerated loss of oocytes, which is complete by the time the infant is 2 years of age. Genetically menopause occurs before menarche and the ovaries are reduced to atrophic fibrous strands, devoid of ova and follicles (streak ovaries). Development of somatic (nongonadal) tissues that reside on the missing/abnormal X chromosome are also severely affected. For example short stature is caused by a deletion of the Xp chromosome and the deletion of Xq causes gonadal dysfunction <ref>Pathologic Basis of Disease, 8th Ed. V. Kumar, R. Cotran & S Robbins (2007), Saunders & Co.</ref>.

[[File:Karyotype.jpg|200px|thumb|left|The arrow indicates the presence of only one X chromosome
in Karyotype <ref>www.ncbi.nlm.nih.gov/pmc/articles/PMC2910953/figure/F0002/</ref>.]]

The most frequent clinical feature is short stature and gonadal dysgenesis. Other features may include [[#Glossary4 | '''coarctation''']] of the aorta, renal anomalies, neck webbing, and lymphoedema. The affected organ systems and tissues may be effected to a lesser or greater extent. In most cases each person who has TS all vary in their clinical phenotype. In recent years there has been increased interest in TS due to the introduction of growth hormone treatment. There has been marked improvement in the understanding of this condition as advances in molecular genetic techniques occur. However, there still needs for further research. A multidisciplinary approach to treatment is important to improve the quality of life of girls with TS <ref name="PMID16544046"><pubmed>16544046</pubmed></ref>.

== Epidemiology ==

Turner Syndrome affects about 1 in 2000 live-born females. There are three types of karyotypic abnormalities but the most frequently seen is where the entire X chromosome is missing resulting in 45 X [[#Glossary17 | '''karyotype''']]. The remaining third have structural abnormalities of the X chromosomes and two thirds are mosaics. Whereby, the maternal X is retained in two-thirds of women and the paternal X in the remainder.
The phenotype of TS varies but involves anomalies of the sex chromosome. It could be caused by the limited amount of genetic material in these abnormal chromosomes. Turner Syndrome can be transmitted from mother to daughter, and thus could be described as a heredity linked syndrome <ref name="PMID16544046"/>.

The loss of one of the sex chromosomes of TS occurs after the zygote has formed or just after the fusion of the [[#Glossary10 | '''gametes''']]. In 70-80% of cases the retained X is from the mother. In such circumstances it has lead to the different phenotypic expression of the genes present on the X chromosome depending if it came from the mother or father.
The morphological differences from those retaining the maternal compared to retaining the paternal X have shown to have a greater incidence of cardiovascular anomalies and neck webbing.
The missing sex chromosome could be either an X or a Y. This has clinical implications because if the Y material is present there is a risk of up to 30% of [[#Glossary11 | '''gonadoblastoma''']] developing in the dysgenetic gonads. This is because the 'gonadoblastoma locus' is on the Y chromosome which is believed to be situated on the long arm of the Y just below the centromere.
Another factor affecting the phenotype in Turner syndrome is the inactivation of the abnormal X chromosomes. In a normal fetus there should be only one X chromosome that is active in each cell <ref>Wade, Nicholas (2009-09-15). '''"New Clues to Sex Anomalies in How Y Chromosomes Are Copied"'''. The New York Times. Retrieved 2010-05-26. http://www.nytimes.com/2009/09/15/science/15chrom.html?pagewanted=1&_r=1&hpw</ref>.

[[File:Stats abnormal.jpg]]

Abnormalities associated with Turner Syndrome <ref name="PMID16544046"/>.

== Etiology ==
[[File:nondisjunction.jpg|850px|thumb|right|alt text|This figure shows the progeny created from normal disjunction (A), and non-disjunction during both Meiosis I (B) and Meiosis II (C).]]

Causation of Turner Syndrome (TS) can be traced back to the stages of sex-cell development. When sex cells divide through a process called [[#Glossary18 | '''meiosis''']] to create gametes, either a [[#Glossary12 | '''haploid''']] egg (for females) or sperm (for males) two divisions occur, Meiosis I and Meiosis II. Meiosis is the main process which helps create the vast genetic diversity within all populations by allowing [[#Glossary25 | '''recombination''']] and [[#Glossary24 | '''random assortment''']]. During Meiosis I [[#Glossary14 | '''homologous chromosomes''']] are separated; following Meiosis I, [[#Glossary27 | '''sister chromatids''']] separate during Meiosis II. If during either stage of Meiosis I or II the homologous chromosomes or sister chromatids, respectively, do not fully separate, a phenomenon can occur called [[#Glossary21 | '''nondisjunction''']]. Nondisjunction causes an uneven distribution of genetic material to each daughter nuclei. When an uneven distribution is such that one of the gametes does not have any of a chromosome, it can combine with another normal gamete to create a fertilized egg with only one chromosome as opposed to the normal two that are found in human cells; this is called a monosomy. When this occurs in the sex chromosomes leaving only a single X chromosome (X0 genotype) Turner Syndrome is created, leaving only 45 chromosomes in the zygote rather than the normal 46.

[[File:22+23=45.jpg|350px|thumb|left|22 chromosomal egg + 23 chromosomal sperm = 45 chromsomes in zygote instead of normal 46.]]
Turner Syndrome can also be created by partial monosomy or disjunctions, meaning that although a whole X chromosome is not missing, portions of it are not present or are non-functional, rendering the chromosome useless. Any disjunction seems to be completely sporadic and have yet to be attributed to any genetic link. The only thing known for sure is that during conception a portion of or the whole second sex chromosome is not conveyed to the zygote.<ref><pubmed>7763055</pubmed></ref> Because at least one X chromosome is necessary for vital functions, this condition can only be found in females.

== Clinical Manifestations ==

The following are a list of characteristics and diseases which tend to accompany, be caused by, or be related to Turner Syndrome.

===Physical Attributes:===
*congenital malformations (heart, urinary system, face, neck, ears) <ref name="PMID16929365"><pubmed>16929365</pubmed></ref>
*gonadal dysgenesis (causes estrogen deficiencies, which can cause infertility) <ref name="PMID16544046"/>
*increased risk of fractures <ref name="PMID16624607"><pubmed>16624607</pubmed></ref>
*low cortical bone mineral density (BMD) <ref name="PMID16624607"/>
*middle ear infections <ref name="PMID16929365"/>
*premature ovarian failure <ref name="PMID16544046"/>
*short/reduced stature <ref name="PMID16544046"/>
*webbed neck <ref name="PMID17562588"><pubmed>17562588</pubmed></ref>

===Decreased Cognition:===
*emotion processing difficulties <ref name="PMID20014362"><pubmed>20014362</pubmed></ref>
*increased impulsivity <ref name="PMID19750135"><pubmed>19750135</pubmed></ref>
*low IQ score <ref name="PMID19750135"/>
*nonverbal learning disability (slow math calculations)<ref name="PMID20014362"/>
*social cognition difficulties <ref name="PMID20014362"/>
*visuoperception/visuoconstruction deficit (identifying and locating is difficult due to poor visual working memory) <ref name="PMID19750135"/>

===Increased Risk of:===
*cirrhosis of the liver <ref name="PMID16929365"/>
*colon and rectal cancers <ref name="PMID16929365"/>
*hypothyroidism <ref name="PMID11844747"><pubmed>11844747</pubmed></ref>
*inflammatory bowel disease <ref name="PMID11844747"/>
*morbidity and mortality <ref name="PMID16544046"/>
*neurovascular disease <ref name="PMID16929365"/>
*osteoporosis <ref name="PMID16929365"/>
*ovarian failure <ref name="PMID17562588"/>
*renal and gastrointestinal disease <ref name="PMID11844747"/>

===Prone to Develop Autoimmune Conditions:===
*alopecia areata <ref name="PMID12602969"><pubmed>12602969</pubmed></ref>
*coeliac disease (CD) <ref><pubmed>12466343</pubmed></ref>
*psoriasis <ref name="PMID12602969"/>
*thyroiditis <ref name="PMID16544046"/>
*type 1 diabetes <ref name="PMID16544046"/>

===Cardiac Abnormalities:===
(most serious/life threatening medical problems created by Turner Syndrome)
*absence of portal vein <ref><pubmed>16612647</pubmed></ref>
*aortic dilatation and dissection <ref name="PMID16929365"/>
*arrhythmias <ref><pubmed>17015510</pubmed></ref>
*arteriosclerosis <ref name="PMID17562588"/>
*biscuspid aortic valves <ref name="PMID17562588"/>
*coarctation of the aorta <ref name="PMID17562588"/>
*hypertension <ref name="PMID17562588"/>
*ischemic heart disease <ref name="PMID16929365"/>
*mitral valve prolapsed <ref name="PMID17562588"/>

== Diagnostic Procedures ==

===Diagnostic Definition===

[[File:Turner Syndrome X Chromosome Variations.jpg|thumb|right|Variations of the Second X Chromosome in Turner Syndrome]]
Turner syndrome is diagnosed through both an evaluation of physical features and by analysis of the second sex chromosome. The two criteria must be met for classification of Turner syndrome, an abnormality in the second sex chromosome must be found and the abnormality must be found to be expressed somehow in the individual's traits. Hence if physical characteristics are not present even when the cytogenetic criterion is met the patient is not diagnosed as having Turner syndrome.<ref name="PMID11443168"><pubmed>11443168</pubmed></ref> In Turner syndrome the second sex chromosome is either:

*Completely absent (45,X)<ref name="PMID16714725"><pubmed>16714725</pubmed></ref><ref name="PMID1511250"><pubmed>1511250</pubmed></ref>
*Partially absent<ref name="PMID16714725"/><ref name="PMID1511250"/>
*Forms an isochromosome (isoXq), possessing a long arm duplication (q) and being devoid of a short arm (p)<ref name="PMID16714725"/>
*In a ring formation (rX)<ref name="PMID16714725"/><ref name="PMID1511250"/>
*Is devoid of the homeobox gene, [[#Glossary26 | '''SHOX''']] (short stature homeobox), the deletion being prior to the junction between Xp22.2 and Xp22.3<ref name="PMID21325865"><pubmed>21325865</pubmed></ref><ref name="PMID11443168"/>

Any of these variations of the second sex chromosome may occur with or without cell line [[#Glossary20 | '''mosaicism''']].
Turner syndrome may be diagnosed prenatally or postnatally, using this genetic diagnostic definition coupled with an appropriate phenotypic evaluation of the individual, as outlined below.<ref name="PMID11443168"/>

===Prenatal Diagnosis===

The prenatal diagnostic tool for Turner syndrome is karyotype screening and testing for phenotype abnormalities. If Turner syndrome is diagnosed prenatally, karyotype screening and an evaluation of the individual's traits should be conducted again postnatally for confirmation of this diagnosis. Turner syndrome is frequently diagnosed after karyotype screening during [[#Glossary5 | '''chorionic villous sampling''']] or [[#Glossary2 | '''amniocentesis''']].<ref name="PMID11443168"/>
The table below outlines various prenatal tests conducted and the indications that may be present in babies with Turner syndrome. Although these techniques and the indications they reveal may highlight Turner syndrome signs, they should not be used as sole diagnostic tools.<ref name="PMID11443168"/>

{|style= align="center" border="1"
|- bgcolor="#99CCCC"
| '''Technique'''
| '''Turner syndrome indications'''
| '''Image'''
|- bgcolor="#FFFFFF"
| '''Ultrasound'''
|
*Increased nuchal translucency <ref name="PMID11443168"/>
*[[#Glossary6 | '''Cystic hygroma''']] <ref name="PMID11443168"/>
*Coarctation of the aorta <ref name="PMID21527014"><pubmed>21527014</pubmed></ref>
*Left-sided cardiac defects <ref name="PMID21527014"/>
*[[#Glossary3 | '''Brachycephaly''']] <ref name="PMID11443168"/>
*Renal anomalies <ref name="PMID16544046"/>
*[[#Glossary23 | '''Polyhydramnios''']] <ref name="PMID16544046"/>
*[[#Glossary22 | '''Oligohydramnios''']] <ref name="PMID11443168"/>
*Growth retardation <ref><pubmed>10599686</pubmed></ref>
|[[File:Turner Syndrome Test Showing Nuchal Translucency.gif|none|thumb|400px|Figure 2: Ultrasound Test Showing Nuchal Translucency.]]
[[File:Turner Syndrome Test Showing Cystic Hygroma.gif|none|thumb|400px|Figure 3: Ultrasound Test Showing Cystic Hygroma.]]
|- bgcolor="#FFFFFF"
|'''Maternal serum screening'''
|
*Abnormal [[#Glossary1 | '''α-fetoprotein''']] levels <ref name="PMID16544046"/>
*Abnormal [[#Glossary16 | '''inhibin A''']] levels <ref name="PMID11443168"/>
*Abnormal [[#Glossary13 | '''hCG''']] levels <ref name="PMID11443168"/>
*Abnormal unconjugated [[#Glossary9 | '''estriol''']] levels <ref name="PMID11443168"/>
|[[File: TurnerSyndromeMaternalSerumSampling.jpg|none|thumb|400px|Figure 4: Maternal Serum Sampling.]]
|}

===Postnatal Diagnosis===

In postnatal diagnosis, karyotype investigation is undertaken for the individual. When a female presents with the following clinical findings, explained in table below, it is recommended that chromosomal analysis is undertaken, so that Turner syndrome may be eliminated<ref name="PMID11443168"/>:
{|sstyle= align="center" border="1"
|- bgcolor="#99CCCC"
| '''Age'''
| '''Phenotypic manifestations/indications'''
| '''Image'''
|- bgcolor="#FFFFFF"
| '''Baby/infant'''
|
*Oedema of the hands or feet<ref name="PMID6753342"/>
*Nuchal folds <ref name="PMID6753342"/>
*Cardiac abnormalities for example aortic dilation, bicuspid aortic valve and aortic coarctation <ref name="PMID21527014"/>
*Low hairline <ref name="PMID6753342"/>
*Low set ears <ref name="PMID6753342"/>
*Small mandible <ref name="PMID6753342"/>
*Gonadal dysgenesis <ref name="PMID21527014"/>
|
|- bgcolor="#FFFFFF"
|'''Child'''
|
*Short stature with low growth velocity <ref name="PMID16714725"/>
*Markedly elevated levels of follicle-stimulating hormone <ref name="PMID11443168"/>
*Turned in elbows <ref name="PMID11443168"/>
*Nail [[#Glossary15 | '''hypoplasia''']] <ref name="PMID11443168"/>
*Hyperconvex uplifted nails <ref name="PMID16714725"/>
*Multiple pigmented benign birthmarks/moles <ref name="PMID11443168"/>
*Characteristic faecies <ref name="PMID6753342"/>
*Short fourth metacarpal <ref name="PMID11443168"/>
*High arched palate <ref name="PMID11443168"/>
*Extensive and chronic inflammation/infection of the ear <ref name="PMID16714725"/>
*Hearing loss <ref name="PMID11443168"/>

|[[File: Turners syndrome 4 year old child.jpg|left|thumb|150px|Figure 5: Four-year-old girl with Turner's syndrome. Note somewhat broad chest, prominent ears and ptosis, but otherwise normal proportion. There is no pronounced neck webbing or edema.]]
|- bgcolor="#FFFFFF"
| '''Adolescent/Adult'''
|
*Absence of breast development by 13 yr of age <ref name="PMID11443168"/>
*Pubertal arrest <ref name="PMID21527014"/>
*Primary or secondary amenorrhoea<ref name="PMID6753342"/>
*Markedly elevated levels of follicle-stimulating hormone <ref name="PMID11443168"/>
*Unexplained short stature <ref name="PMID21527014"/>
*Renal abnormalities <ref name="PMID16714725"/>
*Immune disorders <ref name="PMID16714725"/>

|[[File: Turners syndrome 35 year old woman.jpg|none|thumb|150px|Figure 6: A Thirtyfive-year-old woman with Turner's syndrome. Note increased carrying angle of arms, broad flat chest and sexual infantilism, but the lack of pronounced neck webbing or peripheral edema.]]
|}

Since an absence of the physical signs of puberty and/or growth failure are often seen as normal variations in the population, these possible indications/symptoms of Turner syndrome may not be further investigated by many clinicians.<ref><pubmed>20361125</pubmed></ref> When karyotyping in order to exclude natural cell variation, a sufficient number of cells should be assessed. Whilst a sample of blood will often reveal Turner syndrome, an evaluation of a second tissue sample like the skin is recommend.<ref name="PMID1511250"/>
[[#Glossary7 | '''DNA hybridisation''']] or fluorescent in situ hybridisation should be conducted using a Y centromeric or short arm probe to detect for any additional Y or X chromosomal material.
If there is any of the Y chromosome present, this may initiate gonadoblastoma development, another primary indicator of Turner syndrome. Hence the individual should have both a vaginal [[#Glossary28 | '''ultrasonograph''']] and colour [[#Glossary8 | '''Doppler sonograph''']] of their gonads to detect whether any Y chromosome fragments are present. These tests should be repeated regularly to monitor the patient for any malignancy, if a gonadectomy is not undertaken.<ref name="PMID16714725"/><ref name="PMID11443168"/>

== Treatment ==

=== Cardiac Treatment ===

When patients are confirmed with Turner Syndrome, it is necessary to have a full cardiac evaulation including a physical exam and a echocardiogram. If cardiac abnormalities are found, monitoring by a cardiologist is recommended including regular blood pressure checks<ref name="PMID11443168"/>. Coarctation of the aorta and hypoplastic left heart are quite often very serious issues are need to be dealt with surgically<ref name="Hall">Hall JG, Sybert VP, Williamson RA, et al: Turner's syndrome-Clinical Genetics Conference, Children's Orthopedic Hospital and Medical Center, Seattle, and University of Washington (Specialty Conference). West J Med 1982 Jul; 137:32-44http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1273980/?page=3</ref>.

If no abnormalities are found, blood pressure in Turner Syndrome patients is still routinely checked and a follow up cardiac evaulation is recommended for girls around the age of puberty (12-15)<ref name="PMID11443168"/>.

=== Speech ===

Many Turner Syndrome patients have trouble with their speech. It is necessary for them to be refered to an Ear, Nose and Throat specialist and to a speech therapist to work on improve any speech problems<ref name="PMID11443168"/>.

=== Management of Puberty and Growth ===
The main treatment for growth and pubertal development is Hormone Replacement Therapy. Growth Hormone is adminstered to girls with abnormal growth, resulting in postive growth that is consistent with the expected height of the patient. It is adminstered as early as 2 years of age, but more often in the age group of 9-12 which is in line with the growth spurt that occurs during puberty<ref name="PMID11443168"/>.

Natural estrogen and progesterone are administered to girls when they reach the age of puberty in early adolescence. The age at which this treatment commences varies between individuals, as does the dosage. The adminsteration of estrogen will begin the process of puberty in girls affected by Turner Syndrome and it is important that this begins around the same time as her peers<ref name="Hall"/>. The use of estrogen is often held off if the patient is also undergoing GH treatment so that maximum growth can be achieved, as estrogen will induce the fusion of the epiphyses and limit longitudinal bone growth<ref name="PMID11443168"/>.

Around 10% of nonmosaic and 20% of mosaic women with Turner’s will have spontaneous menses (periods) and may not need to undergo Hormone Replacement to initiate puberty. Around 2-5% of these women will have the potential to fall pregnant naturally<ref name="Hall"/>.

=== Appearance ===

Extreme neck webbing maybe worrying or uncomfortable to women with Turner’s and in some cases plastic surgery is undertaken to fix this problem. Also if convex gorwth of toenails occurs, surgery is conducted so that the woman can wear normal shoes<ref name="Hall"/>.

=== Ongoing Adult Treatment ===

Closely monitoring the health of Turner Syndrome adults is vital in the reduction of morbidity and mortality. An annual physical evalution should be undertaken which includes, blood pressure, heart auscultation, thyroid function, breast exam, and pap smear<ref name="PMID11443168"/>.

Particular attention needs to be taken in the area of weight and obesity in Turner Syndrome women due to their high risk of developing diabetes, osteoporosis and hypertension. Patients are to be encouraged to have a healthy lifestyle including healthy eating and exercise<ref name="PMID11443168"/>.

== Research ==

===Current research===

Since there is no preventative or cure, currently mainly research is being conducted into the areas of symptoms, possible treatments and risks involved with Turner syndrome.

'''Growth hormone therapy in Turner syndrome: its affect on height, weight and stature.'''
*'''Growth hormone effect on body composition in Turner syndrome.(2011)'''<ref><pubmed>21720878</pubmed></ref>: The research findings from this paper conclude that people with Turner syndrome have lower height, higher BMI and higher proportional sitting height and leg length than that of the normal population, no matter whether they undergo hormone replacement therapy or not.
*'''Health-related quality of life of young adults with Turner syndrome following a long-term randomized controlled trial of recombinant human growth hormone.(2011)'''<ref><pubmed>21619701</pubmed></ref>: This study has concluded that all adults with Turner syndrome had a similar quality of life regardless of whether they have a higher stature due to undergoing growth hormone replacement therapy or not. It was hypothesised that height differences did not affect quality of life as the individuals seemed to adapt to their own life challenges.
*'''Growth hormone treatment for Turner syndrome in Australia reveals that younger age and increased dose interact to improve response.(2011)'''<ref><pubmed>21375553</pubmed></ref>: The research from this study found that growth hormone therapy works most optimally if given earlier in life and at a high dose in the first year of treatment.
*'''Growth hormone treatment before the age of 4 years prevents short stature in young girls with Turner syndrome.(2011)'''<ref><pubmed>21398400</pubmed></ref>: Another study which confers that the early introduction of growth hormone therapy is most efficacious. However the individual's glucose metabolism should be monitored as the hormones may affect glucose tolerance transiently.

'''Oestrogen hormone replacement therapy in Turner syndrome: the adequate dosage and its effect on uterine development, breast development, bone mineral density and sexual characteristics.'''
*'''Growth hormone plus childhood low-dose estrogen in Turner's syndrome.(2011)'''<ref><pubmed>21449786</pubmed></ref>: This study indicates that undergoing both growth hormone and oestrogen therapy together may help increase the efficacy of each (increasing growth in height and pubertal development) more than when they act alone.
*'''Estrogen requirements in girls with Turner syndrome; how low is enough for initiating puberty and uterine development?(2011)'''<ref><pubmed>21793702</pubmed></ref>: This study assessed the minimal dosage of estrogen that is required to bring about desired pubertal development in girls with Turner syndrome.
*'''Puberty induction in Turner syndrome: results of oestrogen treatment on development of secondary sexual characteristics, uterine dimensions and serum hormone levels.(2009)'''<ref><pubmed>19200215</pubmed></ref>: It was found that uterus of women with Turner syndrome who had undergone oestrogen was underdeveloped, however the exact cause of this needs to be further researched.

'''Pregnancy and Turner syndrome: evaluation and treatment of risks involved with pregnancy for: the mothers of Turner syndrome babies, for individuals with Turner syndrome and for the babies of individuals with Turner syndrome.'''
*'''Familial occurrence of Turner syndrome: casual event or increased risk?(2011)'''<ref><pubmed>21648298</pubmed></ref>: This research examined whether there is a higher probability of having a second child with Turner syndrome and concluded that there is evidence in the small cohort that they used of a greater probability. It is suggested that a larger study be conducted to look further into these findings.that
*'''Obstetric Outcomes in Women with Turner Karyotype.(2011)'''<ref><pubmed>21865365</pubmed></ref>: In this study it was found that women with Turner syndrome had shorter pregnancies than that of a control group, but no other marked difference was observed between the groups.
*'''Outcomes of spontaneous and assisted pregnancies in Turner syndrome: the U.S. National Institutes of Health experience.(2011)'''<ref><pubmed>21496813</pubmed></ref>: This paper examined a number of pregnant women with Turner syndrome, some who incidentally went through puberty even though they had no hormone replacement therapy and another group that had undertaken hormone replacement therapy. Though there were not many complications in either group, the groups were small in number and one mother did have cardiovascular difficulties later on in life. Hence a thorough examination of pregnant Turner syndrome women should be conducted prior to conception.
*'''Turner's syndrome and pregnancy: has the 45,X/47,XXX mosaicism a different prognosis? Own clinical experience and literature review.(2011)'''<ref><pubmed>20923275</pubmed></ref>: This article assessed the prognosis of pregnant women with Turner syndrome. They concluded that spontaneous pregnancy increases the risk of the baby having phenotypic and chromosomal abnormalities compared with women having assisted reproductive therapies.

===Future research===

Future research needs to be conducted in the following areas: to follow up on the suggestions given in the conclusions of current research papers as outlined in the prior section and also into how the care system is functioning for Turner syndrome individuals as outlined below.

*'''Medical Care of Girls with Turner Syndrome: Where are we Lacking?(2011)'''<ref><pubmed>21454226</pubmed></ref>: This research found that a large proportion (>50%) of people with Turner syndrome are not given adequate information upon diagnosis or screenings for complications and symptoms. Therefore it is suggested in order to rectify this issue that more education should be given to physicians on the syndrome
*'''Standardized multidisciplinary evaluation yields significant previously undiagnosed morbidity in adult women with turner syndrome.(2011)'''<ref><pubmed>21752892</pubmed></ref> and '''Turner's syndrome requires multidisciplinary approach.(2009)'''<ref><pubmed>19514616</pubmed></ref>: These article evaluate the need for a multidisciplinary approach to treatment of Turner syndrome. Since the symptoms can be wide ranging and severe, it is difficult but necessary for all of them to be examined in each individual. Hence a greater care plan for individuals should be implemented upon diagnosis.

== Glossary ==

*<div id="Glossary1"></div>'''Alpha-fetoprotein''' is a protein with an unknown function. It makes up, up to one third of the protein serum levels found in the second trimester of pregnancy and in neural tube defects, these alpha-fetoprotein levels are elevated. <ref name="McPherson">McPherson, R 2011, ''McPherson: Henry's Clinical Diagnosis and Management by Laboratory Methods, 22nd ed.'', ebook, accessed 15 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-1-4377-0974-2..C2009-0-45915-4--TOP&isbn=978-1-4377-0974-2&uniqId=282556246-14 </ref>

*<div id="Glossary2"></div>'''Amniocentesis''' is a prenatal diagnostic tool. The procedure involves the sampling of amniotic fluid from the amniotic sac using a syringe, that is then tested for a number of abnormalities. <ref name="Moore">Moore, K & Persaud, T 2007, ''Moore & Persaud: Before We Are Born, 7th ed.'', ebook, accessed 15 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?eid=4-u1.0-B978-1-4160-3705-7..X5001-3--TOP&isbn=978-1-4160-3705-7&about=true&uniqId=282556246-15</ref>

*<div id="Glossary3"></div>'''Brachycephaly''' is a condition where the coronal suture of the skull fuses prematurely. Since the skull is unable to expand any further in the anterior-posterior directions due to this closure, it grows to an abnormal size in in the lateral dimension.<ref>Flint, P 2010, ''Flint: Cummings Otolaryngology: Head & Neck Surgery, 5th ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-0-323-05283-2..00186-5--s0045&isbn=978-0-323-05283-2&uniqId=282726024-5</ref>

*<div id="Glossary4"></div>'''Coarctation''' of the aorta is an abnormality where the aorta is constricted at one or various sections. This can be caused by genetic and/or environmental factors.<ref name="Moore"/>

*<div id="Glossary5"></div>'''Chorionic villous sampling''' is a prenatal diagnostic tool which can be used from 7 weeks after fertilisation. It is used to test for a number of chromosomal abnormalities including X-linked and metabolic disorders.<ref name="Moore"/>

*<div id="Glossary6"></div>'''Cystic hygroma''' is a prenatal abnormality where fluid builds up in the posterior portion of the neck. The body may or may not relieve itself naturally of this accumulation of fluid after birth. <ref>Gabbe, S 2007, ''Gabbe: Obstetrics: Normal and Problem Pregnancies, 5th ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-0-443-06930-7..50011-6--cesec51&isbn=978-0-443-06930-7&uniqId=282726024-10</ref>

*<div id="Glossary7"></div>'''DNA-DNA hybridisation''' is a technique used to compare the similarities and differences between two sets of genes.<ref>Long, S 2009, ''Bradley: Neurology in Clinical Practice, 5th ed.Long: Principles and Practice of Pediatric Infectious Diseases Revised Reprint, 3rd ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-7020-3468-8..C2009-0-41479-X&isbn=978-0-7020-3468-8&uniqId=282726024-19#4-u1.0-B978-0-7020-3468-8..C2009-0-41479-X--TOP</ref>

*<div id="Glossary8"></div>'''Doppler sonography''' uses the doppler effect to help image and measure blood flow pattern in the patient.<ref name="Bradley">Bradley, W 2008, ''Bradley: Neurology in Clinical Practice, 5th ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-7506-7525-3..X5001-8&isbn=978-0-7506-7525-3&uniqId=282726024-17#4-u1.0-B978-0-7506-7525-3..X5001-8--TOP</ref>

*<div id="Glossary9"></div>'''Estriol''' is a hormone that is produced in greater amounts during pregnancy especially in the second and third trimester. One of its main functions is to assist with blood flow in the placenta and uterus.<ref name="McPherson"/>

*<div id="Glossary10"></div>'''Gametes''' are reproductive (sex) cells (ie: eggs and sperm) that can unite to form a new cell called a zygote. <ref name="Schoenwolf">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H 2009 “Larsen’s Human Embryology”, 4th ed.'', ebook, accessed 22 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-443-06811-9..10001-6&isbn=978-0-443-06811-9&uniqId=283289096-4#4-u1.0-B978-0-443-06811-9..10001-6--b0020</ref>

*<div id="Glossary11"></div>'''Gonadoblastoma''' is an abnormal proliferation of gonadal cells, that may or may not be malignant.<ref name="Wein">Wein, A 2011, ''Wein: Campbell-Walsh Urology, 10th. ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-1-4160-6911-9..00156-0--s0040&isbn=978-1-4160-6911-9&uniqId=282726024-29 </ref>

*<div id="Glossary12"></div>'''Haploid''' is the status of a cell having only a single set of unpaired chromosomes, or half the number of chromosomes contained in typical body cells. <ref name="Schoenwolf"/>

*<div id="Glossary13"></div>'''hCG''' is the abbreviation for human chorionic gonadotropin. It is a hormone that functions in the early stage of pregnancy to maintain the blood supply to the corpus luteum.<ref name="McPherson"/>

*<div id="Glossary14"></div>'''Homologous chromosomes''' are pairs of chromosomes, one each obtained from maternal and paternal gametes. 46 total chromosome complements are within an organism, 22 pairs of which are homologous chromosomes (called autosomes); the other 2 chromosomes are the sex chromosomes. <ref name="Schoenwolf"/>

*<div id="Glossary15"></div>'''Hypoplasia''' is when an organ or tissue is not completely developed.<ref name="Wein"/>

*<div id="Glossary16"></div>'''Inhibin A''' is a peptide produced by the ovaries and acts to restrain the production of follicle-stimulating hormone.<ref>Melmed, S 2011, ''Melmed: Williams Textbook of Endocrinology, 12th ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-1-4377-0324-5..00045-6&isbn=978-1-4377-0324-5&uniqId=282726024-25 </ref>

*<div id="Glossary17"></div>'''Karyotype''' is an individual's set of chromosomes, both their number and appearance.<ref name="McPherson"/>

*<div id="Glossary18"></div>'''Meiosis''' is the specific process of cell division within sex cells which halves the number of chromosomes in the cells through via two cell divisions; this is specific to germ cells only, creating haploid gametes (sex cells) from diploid cells. <ref name="Moore2">Moore, K & Persaud, T 2007, ''Moore & Persaud: The Developing Human, 8th ed.'', ebook, accessed 22 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-3706-4..50005-0--cesec2&isbn=978-1-4160-3706-4&uniqId=283289096-2#4-u1.0-B978-1-4160-3706-4..50005-0--cesec2</ref>

*<div id="Glossary19"></div>'''Monosomy''' is a condition wherein a specific chromosome is completely missing within one gamete that combines with a normal gamete to form a zygote; a chromosome has no homologue, or matching chromosome, to pair with. <ref name="Schoenwolf"/>

*<div id="Glossary20"></div>'''Mosaicism''' is when a particular type or all cells of an individual do not have the same genetic makeup. This is caused by a mutation during embryonic cell division.<ref name="PMID11443168"/>

*<div id="Glossary21"></div>'''Nondisjunction''' is the failure of chromosome pairs to separate entirely during either stage of Meiosis. <ref name="Moore2"/>

*<div id="Glossary22"></div>'''Oligohydramnios''' is a prenatal condition, where there is an insufficient amount of amniotic fluid.<ref name="Moore"/>

*<div id="Glossary23"></div>'''Polyhydramnios''' is a prenatal condition, where there is an excessive amount of amniotic fluid.<ref name="Moore"/>

*<div id="Glossary24"></div>'''Random assortment'''

*<div id="Glossary25"></div>'''Recombination''' is the process which by genetic material is crossed over and switched between two segments of DNA which adds to the genetic diversity of the genome.

*<div id="Glossary26"></div>'''SHOX gene''' is the short stature homeobox gene, that when deficient frequently results in short stature.<ref name="PMID21325865"/>

*<div id="Glossary27"></div>'''Sister chromatids'''

*<div id="Glossary28"></div>'''Ultrasonography''' is a medical technique that employs ultrasound frequencies to visualise a patient's internal bodily structure.<ref name="Bradley"/>

== References ==

<references/>

----
{{2011Projects}}

2011 Group Project 1

2011-10-05T12:08:11Z

Z3060621: /* Introduction */

{{2011ProjectsMH}}
----

== Turner Syndrome ==

--[[User:S8600021|Mark Hill]] 10:44, 8 September 2011 (EST) Some of the existing sub-sections have appropriate content, but there are also empty sub-sections, a total lack of referencing/citation and no glossary.
* The referencing issue needs urgent progress.
* Existing figures/table are appropriate. Table appears to be directly used from an uncited source.
* There needs to be more images in this work.
* Where is the student drawn figure?
* Read http://embryology.med.unsw.edu.au/embryology/index.php?title=Help:Reference_Tutorial#Multiple%20Instances%20on%20Page

== Introduction ==

Turner Syndrome (TS), named after Henry Hubert Turner who first described the syndrome in his paper in 1938,<ref><pubmed>4557013</pubmed></ref> is one of the most commonly occuring chromosomal disorders. It is caused by a complete or partial X [[#Glossary19 | '''monosomy''']] in some or all cells and occurs in approximately 1 in 2000 live female births, however the morbidity rate of spontaneous abortions is 10% and only about 1% of fetuses survive to term.

During normal fetal development, each ovary contain as many as 7 million oocytes. The oocytes gradually reduce to 400,000 during menarche and during menopause fewer than 10,000 remains. However, in Turner syndrome, the ovaries develop normally during embryogenesis but the absence of the second X chromosome leads to an accelerated loss of oocytes, which is complete by the time the infant is 2 years of age. Genetically menopause occurs before menarche and the ovaries are reduced to atrophic fibrous strands, devoid of ova and follicles (streak ovaries). Development of somatic (nongonadal) tissues that reside on the missing/abnormal X chromosome are also severely affected. For example short stature is caused by a deletion of the Xp chromosome and the deletion of Xq causes gonadal dysfunction <ref>Pathologic Basis of Disease, 8th Ed. V. Kumar, R. Cotran & S Robbins (2007), Saunders & Co.</ref>.

[[File:Karyotype.jpg|350px|thumb|left|The arrow indicates the presence of only one X chromosome
in Karyotype <ref>www.ncbi.nlm.nih.gov/pmc/articles/PMC2910953/figure/F0002/</ref>.]]

The most frequent clinical feature is short stature and gonadal dysgenesis. Other features may include [[#Glossary4 | '''coarctation''']] of the aorta, renal anomalies, neck webbing, and lymphoedema. The affected organ systems and tissues may be effected to a lesser or greater extent. In most cases each person who has TS all vary in their clinical phenotype. In recent years there has been increased interest in TS due to the introduction of growth hormone treatment. There has been marked improvement in the understanding of this condition as advances in molecular genetic techniques occur. However, there still needs for further research. A multidisciplinary approach to treatment is important to improve the quality of life of girls with TS <ref name="PMID16544046"><pubmed>16544046</pubmed></ref>.

== Epidemiology ==

Turner Syndrome affects about 1 in 2000 live-born females. There are three types of karyotypic abnormalities but the most frequently seen is where the entire X chromosome is missing resulting in 45 X [[#Glossary17 | '''karyotype''']]. The remaining third have structural abnormalities of the X chromosomes and two thirds are mosaics. Whereby, the maternal X is retained in two-thirds of women and the paternal X in the remainder.
The phenotype of TS varies but involves anomalies of the sex chromosome. It could be caused by the limited amount of genetic material in these abnormal chromosomes. Turner Syndrome can be transmitted from mother to daughter, and thus could be described as a heredity linked syndrome <ref name="PMID16544046"/>.

The loss of one of the sex chromosomes of TS occurs after the zygote has formed or just after the fusion of the [[#Glossary10 | '''gametes''']]. In 70-80% of cases the retained X is from the mother. In such circumstances it has lead to the different phenotypic expression of the genes present on the X chromosome depending if it came from the mother or father.
The morphological differences from those retaining the maternal compared to retaining the paternal X have shown to have a greater incidence of cardiovascular anomalies and neck webbing.
The missing sex chromosome could be either an X or a Y. This has clinical implications because if the Y material is present there is a risk of up to 30% of [[#Glossary11 | '''gonadoblastoma''']] developing in the dysgenetic gonads. This is because the 'gonadoblastoma locus' is on the Y chromosome which is believed to be situated on the long arm of the Y just below the centromere.
Another factor affecting the phenotype in Turner syndrome is the inactivation of the abnormal X chromosomes. In a normal fetus there should be only one X chromosome that is active in each cell <ref>Wade, Nicholas (2009-09-15). '''"New Clues to Sex Anomalies in How Y Chromosomes Are Copied"'''. The New York Times. Retrieved 2010-05-26. http://www.nytimes.com/2009/09/15/science/15chrom.html?pagewanted=1&_r=1&hpw</ref>.

[[File:Stats abnormal.jpg]]

Abnormalities associated with Turner Syndrome <ref name="PMID16544046"/>.

== Etiology ==
[[File:nondisjunction.jpg|850px|thumb|right|alt text|This figure shows the progeny created from normal disjunction (A), and non-disjunction during both Meiosis I (B) and Meiosis II (C).]]

Causation of Turner Syndrome (TS) can be traced back to the stages of sex-cell development. When sex cells divide through a process called [[#Glossary18 | '''meiosis''']] to create gametes, either a [[#Glossary12 | '''haploid''']] egg (for females) or sperm (for males) two divisions occur, Meiosis I and Meiosis II. Meiosis is the main process which helps create the vast genetic diversity within all populations by allowing [[#Glossary25 | '''recombination''']] and [[#Glossary24 | '''random assortment''']]. During Meiosis I [[#Glossary14 | '''homologous chromosomes''']] are separated; following Meiosis I, [[#Glossary27 | '''sister chromatids''']] separate during Meiosis II. If during either stage of Meiosis I or II the homologous chromosomes or sister chromatids, respectively, do not fully separate, a phenomenon can occur called [[#Glossary21 | '''nondisjunction''']]. Nondisjunction causes an uneven distribution of genetic material to each daughter nuclei. When an uneven distribution is such that one of the gametes does not have any of a chromosome, it can combine with another normal gamete to create a fertilized egg with only one chromosome as opposed to the normal two that are found in human cells; this is called a monosomy. When this occurs in the sex chromosomes leaving only a single X chromosome (X0 genotype) Turner Syndrome is created, leaving only 45 chromosomes in the zygote rather than the normal 46.

[[File:22+23=45.jpg|350px|thumb|left|22 chromosomal egg + 23 chromosomal sperm = 45 chromsomes in zygote instead of normal 46.]]
Turner Syndrome can also be created by partial monosomy or disjunctions, meaning that although a whole X chromosome is not missing, portions of it are not present or are non-functional, rendering the chromosome useless. Any disjunction seems to be completely sporadic and have yet to be attributed to any genetic link. The only thing known for sure is that during conception a portion of or the whole second sex chromosome is not conveyed to the zygote.<ref><pubmed>7763055</pubmed></ref> Because at least one X chromosome is necessary for vital functions, this condition can only be found in females.

== Clinical Manifestations ==

The following are a list of characteristics and diseases which tend to accompany, be caused by, or be related to Turner Syndrome.

===Physical Attributes:===
*congenital malformations (heart, urinary system, face, neck, ears) <ref name="PMID16929365"><pubmed>16929365</pubmed></ref>
*gonadal dysgenesis (causes estrogen deficiencies, which can cause infertility) <ref name="PMID16544046"/>
*increased risk of fractures <ref name="PMID16624607"><pubmed>16624607</pubmed></ref>
*low cortical bone mineral density (BMD) <ref name="PMID16624607"/>
*middle ear infections <ref name="PMID16929365"/>
*premature ovarian failure <ref name="PMID16544046"/>
*short/reduced stature <ref name="PMID16544046"/>
*webbed neck <ref name="PMID17562588"><pubmed>17562588</pubmed></ref>

===Decreased Cognition:===
*emotion processing difficulties <ref name="PMID20014362"><pubmed>20014362</pubmed></ref>
*increased impulsivity <ref name="PMID19750135"><pubmed>19750135</pubmed></ref>
*low IQ score <ref name="PMID19750135"/>
*nonverbal learning disability (slow math calculations)<ref name="PMID20014362"/>
*social cognition difficulties <ref name="PMID20014362"/>
*visuoperception/visuoconstruction deficit (identifying and locating is difficult due to poor visual working memory) <ref name="PMID19750135"/>

===Increased Risk of:===
*cirrhosis of the liver <ref name="PMID16929365"/>
*colon and rectal cancers <ref name="PMID16929365"/>
*hypothyroidism <ref name="PMID11844747"><pubmed>11844747</pubmed></ref>
*inflammatory bowel disease <ref name="PMID11844747"/>
*morbidity and mortality <ref name="PMID16544046"/>
*neurovascular disease <ref name="PMID16929365"/>
*osteoporosis <ref name="PMID16929365"/>
*ovarian failure <ref name="PMID17562588"/>
*renal and gastrointestinal disease <ref name="PMID11844747"/>

===Prone to Develop Autoimmune Conditions:===
*alopecia areata <ref name="PMID12602969"><pubmed>12602969</pubmed></ref>
*coeliac disease (CD) <ref><pubmed>12466343</pubmed></ref>
*psoriasis <ref name="PMID12602969"/>
*thyroiditis <ref name="PMID16544046"/>
*type 1 diabetes <ref name="PMID16544046"/>

===Cardiac Abnormalities:===
(most serious/life threatening medical problems created by Turner Syndrome)
*absence of portal vein <ref><pubmed>16612647</pubmed></ref>
*aortic dilatation and dissection <ref name="PMID16929365"/>
*arrhythmias <ref><pubmed>17015510</pubmed></ref>
*arteriosclerosis <ref name="PMID17562588"/>
*biscuspid aortic valves <ref name="PMID17562588"/>
*coarctation of the aorta <ref name="PMID17562588"/>
*hypertension <ref name="PMID17562588"/>
*ischemic heart disease <ref name="PMID16929365"/>
*mitral valve prolapsed <ref name="PMID17562588"/>

== Diagnostic Procedures ==

===Diagnostic Definition===

[[File:Turner Syndrome X Chromosome Variations.jpg|thumb|right|Variations of the Second X Chromosome in Turner Syndrome]]
Turner syndrome is diagnosed through both an evaluation of physical features and by analysis of the second sex chromosome. The two criteria must be met for classification of Turner syndrome, an abnormality in the second sex chromosome must be found and the abnormality must be found to be expressed somehow in the individual's traits. Hence if physical characteristics are not present even when the cytogenetic criterion is met the patient is not diagnosed as having Turner syndrome.<ref name="PMID11443168"><pubmed>11443168</pubmed></ref> In Turner syndrome the second sex chromosome is either:

*Completely absent (45,X)<ref name="PMID16714725"><pubmed>16714725</pubmed></ref><ref name="PMID1511250"><pubmed>1511250</pubmed></ref>
*Partially absent<ref name="PMID16714725"/><ref name="PMID1511250"/>
*Forms an isochromosome (isoXq), possessing a long arm duplication (q) and being devoid of a short arm (p)<ref name="PMID16714725"/>
*In a ring formation (rX)<ref name="PMID16714725"/><ref name="PMID1511250"/>
*Is devoid of the homeobox gene, [[#Glossary26 | '''SHOX''']] (short stature homeobox), the deletion being prior to the junction between Xp22.2 and Xp22.3<ref name="PMID21325865"><pubmed>21325865</pubmed></ref><ref name="PMID11443168"/>

Any of these variations of the second sex chromosome may occur with or without cell line [[#Glossary20 | '''mosaicism''']].
Turner syndrome may be diagnosed prenatally or postnatally, using this genetic diagnostic definition coupled with an appropriate phenotypic evaluation of the individual, as outlined below.<ref name="PMID11443168"/>

===Prenatal Diagnosis===

The prenatal diagnostic tool for Turner syndrome is karyotype screening and testing for phenotype abnormalities. If Turner syndrome is diagnosed prenatally, karyotype screening and an evaluation of the individual's traits should be conducted again postnatally for confirmation of this diagnosis. Turner syndrome is frequently diagnosed after karyotype screening during [[#Glossary5 | '''chorionic villous sampling''']] or [[#Glossary2 | '''amniocentesis''']].<ref name="PMID11443168"/>
The table below outlines various prenatal tests conducted and the indications that may be present in babies with Turner syndrome. Although these techniques and the indications they reveal may highlight Turner syndrome signs, they should not be used as sole diagnostic tools.<ref name="PMID11443168"/>

{|style= align="center" border="1"
|- bgcolor="#99CCCC"
| '''Technique'''
| '''Turner syndrome indications'''
| '''Image'''
|- bgcolor="#FFFFFF"
| '''Ultrasound'''
|
*Increased nuchal translucency <ref name="PMID11443168"/>
*[[#Glossary6 | '''Cystic hygroma''']] <ref name="PMID11443168"/>
*Coarctation of the aorta <ref name="PMID21527014"><pubmed>21527014</pubmed></ref>
*Left-sided cardiac defects <ref name="PMID21527014"/>
*[[#Glossary3 | '''Brachycephaly''']] <ref name="PMID11443168"/>
*Renal anomalies <ref name="PMID16544046"/>
*[[#Glossary23 | '''Polyhydramnios''']] <ref name="PMID16544046"/>
*[[#Glossary22 | '''Oligohydramnios''']] <ref name="PMID11443168"/>
*Growth retardation <ref><pubmed>10599686</pubmed></ref>
|[[File:Turner Syndrome Test Showing Nuchal Translucency.gif|none|thumb|400px|Figure 2: Ultrasound Test Showing Nuchal Translucency.]]
[[File:Turner Syndrome Test Showing Cystic Hygroma.gif|none|thumb|400px|Figure 3: Ultrasound Test Showing Cystic Hygroma.]]
|- bgcolor="#FFFFFF"
|'''Maternal serum screening'''
|
*Abnormal [[#Glossary1 | '''α-fetoprotein''']] levels <ref name="PMID16544046"/>
*Abnormal [[#Glossary16 | '''inhibin A''']] levels <ref name="PMID11443168"/>
*Abnormal [[#Glossary13 | '''hCG''']] levels <ref name="PMID11443168"/>
*Abnormal unconjugated [[#Glossary9 | '''estriol''']] levels <ref name="PMID11443168"/>
|[[File: TurnerSyndromeMaternalSerumSampling.jpg|none|thumb|400px|Figure 4: Maternal Serum Sampling.]]
|}

===Postnatal Diagnosis===

In postnatal diagnosis, karyotype investigation is undertaken for the individual. When a female presents with the following clinical findings, explained in table below, it is recommended that chromosomal analysis is undertaken, so that Turner syndrome may be eliminated<ref name="PMID11443168"/>:
{|sstyle= align="center" border="1"
|- bgcolor="#99CCCC"
| '''Age'''
| '''Phenotypic manifestations/indications'''
| '''Image'''
|- bgcolor="#FFFFFF"
| '''Baby/infant'''
|
*Oedema of the hands or feet<ref name="PMID6753342"/>
*Nuchal folds <ref name="PMID6753342"/>
*Cardiac abnormalities for example aortic dilation, bicuspid aortic valve and aortic coarctation <ref name="PMID21527014"/>
*Low hairline <ref name="PMID6753342"/>
*Low set ears <ref name="PMID6753342"/>
*Small mandible <ref name="PMID6753342"/>
*Gonadal dysgenesis <ref name="PMID21527014"/>
|
|- bgcolor="#FFFFFF"
|'''Child'''
|
*Short stature with low growth velocity <ref name="PMID16714725"/>
*Markedly elevated levels of follicle-stimulating hormone <ref name="PMID11443168"/>
*Turned in elbows <ref name="PMID11443168"/>
*Nail [[#Glossary15 | '''hypoplasia''']] <ref name="PMID11443168"/>
*Hyperconvex uplifted nails <ref name="PMID16714725"/>
*Multiple pigmented benign birthmarks/moles <ref name="PMID11443168"/>
*Characteristic faecies <ref name="PMID6753342"/>
*Short fourth metacarpal <ref name="PMID11443168"/>
*High arched palate <ref name="PMID11443168"/>
*Extensive and chronic inflammation/infection of the ear <ref name="PMID16714725"/>
*Hearing loss <ref name="PMID11443168"/>

|[[File: Turners syndrome 4 year old child.jpg|left|thumb|150px|Figure 5: Four-year-old girl with Turner's syndrome. Note somewhat broad chest, prominent ears and ptosis, but otherwise normal proportion. There is no pronounced neck webbing or edema.]]
|- bgcolor="#FFFFFF"
| '''Adolescent/Adult'''
|
*Absence of breast development by 13 yr of age <ref name="PMID11443168"/>
*Pubertal arrest <ref name="PMID21527014"/>
*Primary or secondary amenorrhoea<ref name="PMID6753342"/>
*Markedly elevated levels of follicle-stimulating hormone <ref name="PMID11443168"/>
*Unexplained short stature <ref name="PMID21527014"/>
*Renal abnormalities <ref name="PMID16714725"/>
*Immune disorders <ref name="PMID16714725"/>

|[[File: Turners syndrome 35 year old woman.jpg|none|thumb|150px|Figure 6: A Thirtyfive-year-old woman with Turner's syndrome. Note increased carrying angle of arms, broad flat chest and sexual infantilism, but the lack of pronounced neck webbing or peripheral edema.]]
|}

Since an absence of the physical signs of puberty and/or growth failure are often seen as normal variations in the population, these possible indications/symptoms of Turner syndrome may not be further investigated by many clinicians.<ref><pubmed>20361125</pubmed></ref> When karyotyping in order to exclude natural cell variation, a sufficient number of cells should be assessed. Whilst a sample of blood will often reveal Turner syndrome, an evaluation of a second tissue sample like the skin is recommend.<ref name="PMID1511250"/>
[[#Glossary7 | '''DNA hybridisation''']] or fluorescent in situ hybridisation should be conducted using a Y centromeric or short arm probe to detect for any additional Y or X chromosomal material.
If there is any of the Y chromosome present, this may initiate gonadoblastoma development, another primary indicator of Turner syndrome. Hence the individual should have both a vaginal [[#Glossary28 | '''ultrasonograph''']] and colour [[#Glossary8 | '''Doppler sonograph''']] of their gonads to detect whether any Y chromosome fragments are present. These tests should be repeated regularly to monitor the patient for any malignancy, if a gonadectomy is not undertaken.<ref name="PMID16714725"/><ref name="PMID11443168"/>

== Treatment ==

=== Cardiac Treatment ===

When patients are confirmed with Turner Syndrome, it is necessary to have a full cardiac evaulation including a physical exam and a echocardiogram. If cardiac abnormalities are found, monitoring by a cardiologist is recommended including regular blood pressure checks<ref name="PMID11443168"/>. Coarctation of the aorta and hypoplastic left heart are quite often very serious issues are need to be dealt with surgically<ref name="Hall">Hall JG, Sybert VP, Williamson RA, et al: Turner's syndrome-Clinical Genetics Conference, Children's Orthopedic Hospital and Medical Center, Seattle, and University of Washington (Specialty Conference). West J Med 1982 Jul; 137:32-44http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1273980/?page=3</ref>.

If no abnormalities are found, blood pressure in Turner Syndrome patients is still routinely checked and a follow up cardiac evaulation is recommended for girls around the age of puberty (12-15)<ref name="PMID11443168"/>.

=== Speech ===

Many Turner Syndrome patients have trouble with their speech. It is necessary for them to be refered to an Ear, Nose and Throat specialist and to a speech therapist to work on improve any speech problems<ref name="PMID11443168"/>.

=== Management of Puberty and Growth ===
The main treatment for growth and pubertal development is Hormone Replacement Therapy. Growth Hormone is adminstered to girls with abnormal growth, resulting in postive growth that is consistent with the expected height of the patient. It is adminstered as early as 2 years of age, but more often in the age group of 9-12 which is in line with the growth spurt that occurs during puberty<ref name="PMID11443168"/>.

Natural estrogen and progesterone are administered to girls when they reach the age of puberty in early adolescence. The age at which this treatment commences varies between individuals, as does the dosage. The adminsteration of estrogen will begin the process of puberty in girls affected by Turner Syndrome and it is important that this begins around the same time as her peers<ref name="Hall"/>. The use of estrogen is often held off if the patient is also undergoing GH treatment so that maximum growth can be achieved, as estrogen will induce the fusion of the epiphyses and limit longitudinal bone growth<ref name="PMID11443168"/>.

Around 10% of nonmosaic and 20% of mosaic women with Turner’s will have spontaneous menses (periods) and may not need to undergo Hormone Replacement to initiate puberty. Around 2-5% of these women will have the potential to fall pregnant naturally<ref name="Hall"/>.

=== Appearance ===

Extreme neck webbing maybe worrying or uncomfortable to women with Turner’s and in some cases plastic surgery is undertaken to fix this problem. Also if convex gorwth of toenails occurs, surgery is conducted so that the woman can wear normal shoes<ref name="Hall"/>.

=== Ongoing Adult Treatment ===

Closely monitoring the health of Turner Syndrome adults is vital in the reduction of morbidity and mortality. An annual physical evalution should be undertaken which includes, blood pressure, heart auscultation, thyroid function, breast exam, and pap smear<ref name="PMID11443168"/>.

Particular attention needs to be taken in the area of weight and obesity in Turner Syndrome women due to their high risk of developing diabetes, osteoporosis and hypertension. Patients are to be encouraged to have a healthy lifestyle including healthy eating and exercise<ref name="PMID11443168"/>.

== Research ==

===Current research===

Since there is no preventative or cure, currently mainly research is being conducted into the areas of symptoms, possible treatments and risks involved with Turner syndrome.

'''Growth hormone therapy in Turner syndrome: its affect on height, weight and stature.'''
*'''Growth hormone effect on body composition in Turner syndrome.(2011)'''<ref><pubmed>21720878</pubmed></ref>: The research findings from this paper conclude that people with Turner syndrome have lower height, higher BMI and higher proportional sitting height and leg length than that of the normal population, no matter whether they undergo hormone replacement therapy or not.
*'''Health-related quality of life of young adults with Turner syndrome following a long-term randomized controlled trial of recombinant human growth hormone.(2011)'''<ref><pubmed>21619701</pubmed></ref>: This study has concluded that all adults with Turner syndrome had a similar quality of life regardless of whether they have a higher stature due to undergoing growth hormone replacement therapy or not. It was hypothesised that height differences did not affect quality of life as the individuals seemed to adapt to their own life challenges.
*'''Growth hormone treatment for Turner syndrome in Australia reveals that younger age and increased dose interact to improve response.(2011)'''<ref><pubmed>21375553</pubmed></ref>: The research from this study found that growth hormone therapy works most optimally if given earlier in life and at a high dose in the first year of treatment.
*'''Growth hormone treatment before the age of 4 years prevents short stature in young girls with Turner syndrome.(2011)'''<ref><pubmed>21398400</pubmed></ref>: Another study which confers that the early introduction of growth hormone therapy is most efficacious. However the individual's glucose metabolism should be monitored as the hormones may affect glucose tolerance transiently.

'''Oestrogen hormone replacement therapy in Turner syndrome: the adequate dosage and its effect on uterine development, breast development, bone mineral density and sexual characteristics.'''
*'''Growth hormone plus childhood low-dose estrogen in Turner's syndrome.(2011)'''<ref><pubmed>21449786</pubmed></ref>: This study indicates that undergoing both growth hormone and oestrogen therapy together may help increase the efficacy of each (increasing growth in height and pubertal development) more than when they act alone.
*'''Estrogen requirements in girls with Turner syndrome; how low is enough for initiating puberty and uterine development?(2011)'''<ref><pubmed>21793702</pubmed></ref>: This study assessed the minimal dosage of estrogen that is required to bring about desired pubertal development in girls with Turner syndrome.
*'''Puberty induction in Turner syndrome: results of oestrogen treatment on development of secondary sexual characteristics, uterine dimensions and serum hormone levels.(2009)'''<ref><pubmed>19200215</pubmed></ref>: It was found that uterus of women with Turner syndrome who had undergone oestrogen was underdeveloped, however the exact cause of this needs to be further researched.

'''Pregnancy and Turner syndrome: evaluation and treatment of risks involved with pregnancy for: the mothers of Turner syndrome babies, for individuals with Turner syndrome and for the babies of individuals with Turner syndrome.'''
*'''Familial occurrence of Turner syndrome: casual event or increased risk?(2011)'''<ref><pubmed>21648298</pubmed></ref>: This research examined whether there is a higher probability of having a second child with Turner syndrome and concluded that there is evidence in the small cohort that they used of a greater probability. It is suggested that a larger study be conducted to look further into these findings.that
*'''Obstetric Outcomes in Women with Turner Karyotype.(2011)'''<ref><pubmed>21865365</pubmed></ref>: In this study it was found that women with Turner syndrome had shorter pregnancies than that of a control group, but no other marked difference was observed between the groups.
*'''Outcomes of spontaneous and assisted pregnancies in Turner syndrome: the U.S. National Institutes of Health experience.(2011)'''<ref><pubmed>21496813</pubmed></ref>: This paper examined a number of pregnant women with Turner syndrome, some who incidentally went through puberty even though they had no hormone replacement therapy and another group that had undertaken hormone replacement therapy. Though there were not many complications in either group, the groups were small in number and one mother did have cardiovascular difficulties later on in life. Hence a thorough examination of pregnant Turner syndrome women should be conducted prior to conception.
*'''Turner's syndrome and pregnancy: has the 45,X/47,XXX mosaicism a different prognosis? Own clinical experience and literature review.(2011)'''<ref><pubmed>20923275</pubmed></ref>: This article assessed the prognosis of pregnant women with Turner syndrome. They concluded that spontaneous pregnancy increases the risk of the baby having phenotypic and chromosomal abnormalities compared with women having assisted reproductive therapies.

===Future research===

Future research needs to be conducted in the following areas: to follow up on the suggestions given in the conclusions of current research papers as outlined in the prior section and also into how the care system is functioning for Turner syndrome individuals as outlined below.

*'''Medical Care of Girls with Turner Syndrome: Where are we Lacking?(2011)'''<ref><pubmed>21454226</pubmed></ref>: This research found that a large proportion (>50%) of people with Turner syndrome are not given adequate information upon diagnosis or screenings for complications and symptoms. Therefore it is suggested in order to rectify this issue that more education should be given to physicians on the syndrome
*'''Standardized multidisciplinary evaluation yields significant previously undiagnosed morbidity in adult women with turner syndrome.(2011)'''<ref><pubmed>21752892</pubmed></ref> and '''Turner's syndrome requires multidisciplinary approach.(2009)'''<ref><pubmed>19514616</pubmed></ref>: These article evaluate the need for a multidisciplinary approach to treatment of Turner syndrome. Since the symptoms can be wide ranging and severe, it is difficult but necessary for all of them to be examined in each individual. Hence a greater care plan for individuals should be implemented upon diagnosis.

== Glossary ==

*<div id="Glossary1"></div>'''Alpha-fetoprotein''' is a protein with an unknown function. It makes up, up to one third of the protein serum levels found in the second trimester of pregnancy and in neural tube defects, these alpha-fetoprotein levels are elevated. <ref name="McPherson">McPherson, R 2011, ''McPherson: Henry's Clinical Diagnosis and Management by Laboratory Methods, 22nd ed.'', ebook, accessed 15 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-1-4377-0974-2..C2009-0-45915-4--TOP&isbn=978-1-4377-0974-2&uniqId=282556246-14 </ref>

*<div id="Glossary2"></div>'''Amniocentesis''' is a prenatal diagnostic tool. The procedure involves the sampling of amniotic fluid from the amniotic sac using a syringe, that is then tested for a number of abnormalities. <ref name="Moore">Moore, K & Persaud, T 2007, ''Moore & Persaud: Before We Are Born, 7th ed.'', ebook, accessed 15 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?eid=4-u1.0-B978-1-4160-3705-7..X5001-3--TOP&isbn=978-1-4160-3705-7&about=true&uniqId=282556246-15</ref>

*<div id="Glossary3"></div>'''Brachycephaly''' is a condition where the coronal suture of the skull fuses prematurely. Since the skull is unable to expand any further in the anterior-posterior directions due to this closure, it grows to an abnormal size in in the lateral dimension.<ref>Flint, P 2010, ''Flint: Cummings Otolaryngology: Head & Neck Surgery, 5th ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-0-323-05283-2..00186-5--s0045&isbn=978-0-323-05283-2&uniqId=282726024-5</ref>

*<div id="Glossary4"></div>'''Coarctation''' of the aorta is an abnormality where the aorta is constricted at one or various sections. This can be caused by genetic and/or environmental factors.<ref name="Moore"/>

*<div id="Glossary5"></div>'''Chorionic villous sampling''' is a prenatal diagnostic tool which can be used from 7 weeks after fertilisation. It is used to test for a number of chromosomal abnormalities including X-linked and metabolic disorders.<ref name="Moore"/>

*<div id="Glossary6"></div>'''Cystic hygroma''' is a prenatal abnormality where fluid builds up in the posterior portion of the neck. The body may or may not relieve itself naturally of this accumulation of fluid after birth. <ref>Gabbe, S 2007, ''Gabbe: Obstetrics: Normal and Problem Pregnancies, 5th ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-0-443-06930-7..50011-6--cesec51&isbn=978-0-443-06930-7&uniqId=282726024-10</ref>

*<div id="Glossary7"></div>'''DNA-DNA hybridisation''' is a technique used to compare the similarities and differences between two sets of genes.<ref>Long, S 2009, ''Bradley: Neurology in Clinical Practice, 5th ed.Long: Principles and Practice of Pediatric Infectious Diseases Revised Reprint, 3rd ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-7020-3468-8..C2009-0-41479-X&isbn=978-0-7020-3468-8&uniqId=282726024-19#4-u1.0-B978-0-7020-3468-8..C2009-0-41479-X--TOP</ref>

*<div id="Glossary8"></div>'''Doppler sonography''' uses the doppler effect to help image and measure blood flow pattern in the patient.<ref name="Bradley">Bradley, W 2008, ''Bradley: Neurology in Clinical Practice, 5th ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-7506-7525-3..X5001-8&isbn=978-0-7506-7525-3&uniqId=282726024-17#4-u1.0-B978-0-7506-7525-3..X5001-8--TOP</ref>

*<div id="Glossary9"></div>'''Estriol''' is a hormone that is produced in greater amounts during pregnancy especially in the second and third trimester. One of its main functions is to assist with blood flow in the placenta and uterus.<ref name="McPherson"/>

*<div id="Glossary10"></div>'''Gametes''' are reproductive (sex) cells (ie: eggs and sperm) that can unite to form a new cell called a zygote. <ref name="Schoenwolf">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H 2009 “Larsen’s Human Embryology”, 4th ed.'', ebook, accessed 22 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-443-06811-9..10001-6&isbn=978-0-443-06811-9&uniqId=283289096-4#4-u1.0-B978-0-443-06811-9..10001-6--b0020</ref>

*<div id="Glossary11"></div>'''Gonadoblastoma''' is an abnormal proliferation of gonadal cells, that may or may not be malignant.<ref name="Wein">Wein, A 2011, ''Wein: Campbell-Walsh Urology, 10th. ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-1-4160-6911-9..00156-0--s0040&isbn=978-1-4160-6911-9&uniqId=282726024-29 </ref>

*<div id="Glossary12"></div>'''Haploid''' is the status of a cell having only a single set of unpaired chromosomes, or half the number of chromosomes contained in typical body cells. <ref name="Schoenwolf"/>

*<div id="Glossary13"></div>'''hCG''' is the abbreviation for human chorionic gonadotropin. It is a hormone that functions in the early stage of pregnancy to maintain the blood supply to the corpus luteum.<ref name="McPherson"/>

*<div id="Glossary14"></div>'''Homologous chromosomes''' are pairs of chromosomes, one each obtained from maternal and paternal gametes. 46 total chromosome complements are within an organism, 22 pairs of which are homologous chromosomes (called autosomes); the other 2 chromosomes are the sex chromosomes. <ref name="Schoenwolf"/>

*<div id="Glossary15"></div>'''Hypoplasia''' is when an organ or tissue is not completely developed.<ref name="Wein"/>

*<div id="Glossary16"></div>'''Inhibin A''' is a peptide produced by the ovaries and acts to restrain the production of follicle-stimulating hormone.<ref>Melmed, S 2011, ''Melmed: Williams Textbook of Endocrinology, 12th ed.'', ebook, accessed 20 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/about.do?about=true&eid=4-u1.0-B978-1-4377-0324-5..00045-6&isbn=978-1-4377-0324-5&uniqId=282726024-25 </ref>

*<div id="Glossary17"></div>'''Karyotype''' is an individual's set of chromosomes, both their number and appearance.<ref name="McPherson"/>

*<div id="Glossary18"></div>'''Meiosis''' is the specific process of cell division within sex cells which halves the number of chromosomes in the cells through via two cell divisions; this is specific to germ cells only, creating haploid gametes (sex cells) from diploid cells. <ref name="Moore2">Moore, K & Persaud, T 2007, ''Moore & Persaud: The Developing Human, 8th ed.'', ebook, accessed 22 September 2011 from MD Consult Australia, http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-3706-4..50005-0--cesec2&isbn=978-1-4160-3706-4&uniqId=283289096-2#4-u1.0-B978-1-4160-3706-4..50005-0--cesec2</ref>

*<div id="Glossary19"></div>'''Monosomy''' is a condition wherein a specific chromosome is completely missing within one gamete that combines with a normal gamete to form a zygote; a chromosome has no homologue, or matching chromosome, to pair with. <ref name="Schoenwolf"/>

*<div id="Glossary20"></div>'''Mosaicism''' is when a particular type or all cells of an individual do not have the same genetic makeup. This is caused by a mutation during embryonic cell division.<ref name="PMID11443168"/>

*<div id="Glossary21"></div>'''Nondisjunction''' is the failure of chromosome pairs to separate entirely during either stage of Meiosis. <ref name="Moore2"/>

*<div id="Glossary22"></div>'''Oligohydramnios''' is a prenatal condition, where there is an insufficient amount of amniotic fluid.<ref name="Moore"/>

*<div id="Glossary23"></div>'''Polyhydramnios''' is a prenatal condition, where there is an excessive amount of amniotic fluid.<ref name="Moore"/>

*<div id="Glossary24"></div>'''Random assortment'''

*<div id="Glossary25"></div>'''Recombination''' is the process which by genetic material is crossed over and switched between two segments of DNA which adds to the genetic diversity of the genome.

*<div id="Glossary26"></div>'''SHOX gene''' is the short stature homeobox gene, that when deficient frequently results in short stature.<ref name="PMID21325865"/>

*<div id="Glossary27"></div>'''Sister chromatids'''

*<div id="Glossary28"></div>'''Ultrasonography''' is a medical technique that employs ultrasound frequencies to visualise a patient's internal bodily structure.<ref name="Bradley"/>

== References ==

<references/>

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