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Placenta praevia?(placenta previa?AE) is an?obstetric?complication in which the?placenta?is inserted partially or wholly in lower uterine segment.[1]It can sometimes occur in the later part of the first trimester, but usually during the second or third. It is a leading cause of?antepartum haemorrhage(vaginal?bleeding). It affects approximately 0.4-0.5% of all?labours.[2]In the last trimester of pregnancy the?isthmus?of the?uterus?unfolds and forms the lower segment. In a normal pregnancy the placenta does not overlie. If the placenta does overlie the lower segment, as is the case with placenta praevia, it may shear off and a small section may bleed.EtiopathogenesisExact etiology of placenta praevia is unknown. It is hypothesized to be related to abnormal?vascularisation?of the?endometrium?caused by scarring or?atrophy?from previous trauma, surgery, or infection. These factors may reduce differential growth of lower segment, resulting in less upward shift in placental position as pregnancy advances.[3]GradesTraditionally, four grades of placenta praevia are defined:GradeDescriptionIPlacenta is in lower segment, but the lower edge does not reach?internal osIILower edge of placenta reaches internal os, but does not cover itIIIPlacenta covers internal os partiallyIVPlacenta covers internal os completelyRisk factorsRisk factors with their odds ratioRisk factorOdds ratioMaternal age ≥ 40 (vs. < 20)9.1Illicit drugs2.8≥ 1 previous Cesarean section2.7Parity?≥ 5 (vs. para 0)2.3Parity 2–4 (vs. para 0)1.9Prior abortion1.9Smoking1.6Congenital anomalies1.7Male fetus (vs. female)1.1Pregnancy-induced hypertension0.4The following have been identified as risk factors for placenta praevia:Previous placenta previa (recurrence rate 4-8%),[5]?caesarean delivery,[6]?myomectomy[7]?or endometrium damage caused by?D&C.[5]Alcohol use during pregnancy.[8]Women who have had previous pregnancies, especially a large number of closely spaced pregnancies, are at higher risk due to uterine damage.[7]Smoking during pregnancy;[1]?cocaine use during pregnancy[9][10]Women who are younger than 20 are at higher risk and women older than 35 are at increasing risk as they get older.Women with a large placentae from?twins?or? HYPERLINK "" \o "Erythroblastosis" erythroblastosis?are at higher risk.Race?is a controversial risk factor, with some studies finding that people from Asia and Africa are at higher risk and others finding no difference.Placental pathology ( HYPERLINK "" \o "Velamentous cord insertion" Vellamentous insertion, succinturiate lobes, bipartite i.e. bilobed placenta etc.)[5]Placenta previa is itself a risk factor of?placenta accreta.DiagnosisClinicalHistory may reveal antepartum hemorrhage. Abdominal examination and usually finds the uterus non-tender, soft and relaxed.?Leopold's Maneuvers?may find the fetus in an oblique or breech position or lying transverse as a result of the abnormal position of the placenta. Malpresentation is found in about 35% cases.[12]?Vaginal examinaton is avoided in known cases of placenta praevia.[1]ConfirmatoryPrevia can be confirmed with an?ultrasound.[13]?Transvaginal ultrasound has superior accuracy as compared to transabdominal one, thus allowing measurement of distance between placenta and cervical os. This has rendered traditional classification of placenta praevia obsolete.[14][15][16][17]False positives may be due to following reasons: HYPERLINK "" \l "cite_note-sutton-18" [18]Overfilled bladder compressing lower uterine segmentMyometrial contraction simulating placental tissue in abnormally low locationEarly pregnancy low position, which in third trimester may be entirely normal due to differential growth of the uterus.In such cases, repeat scanning is done after an interval of 15–30 minutes.In parts of the world where ultrasound is unavailable, it is not uncommon to confirm the diagnosis with an examination in the surgical theatre. The proper timing of an examination in theatre is important. If the woman is not bleeding severely she can be managed non-operatively until the 36th week. By this time the baby's chance of survival is as good as at full term.ManagementAn initial assessment to determine the status of the mother and fetus is required. Although mothers used to be treated in the hospital from the first bleeding episode until birth, it is now considered safe to treat placenta praevia on an outpatient basis if the fetus is at less than 30 weeks of gestation, and neither the mother nor the fetus are in distress. Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother are in distress. Blood volume replacement (to maintain blood pressure) and blood plasma replacement (to maintain fibrinogen levels) may be necessary.Mode of deliveryThe mode of delivery is determined by clinical state of the mother, fetus and ultrasound findings. In minor degrees (traditional grade I and II), vaginal delivery is possible.?RCOG?recommends that placenta should be at least 2?cm away from internal os for an attempted vaginal delivery.[19]?When a vaginal delivery is attempted, consultant obstetrician and anesthetists are present in delivery suite. In cases of fetal distress and major degrees (traditional grade III and IV) a caesarean section is indicated. Caesarian section is contraindicated in cases of?disseminated intravascular coagulation. Obstetrician may need to divide the anterior lying placenta. In such cases, blood loss is expected to be high and thus blood and blood products are always kept ready. In rare cases, hysterectomy may be required.[20]ComplicationsMaternalAntepartum hemorrhageMalpresentationAbnormal?placentationPostpartum hemorrhagePlacenta praevia increases the risk of?puerperal sepsis?and?postpartum haemorrhage?because the lower segment to which the placenta was attached contracts less well post-delivery.FetalIUGR (15% incidence)[5]Premature deliveryDeathEpidemiologyPlacenta previa occurs approximately one of every 250 births. One third of all?antepartum hemorrhage?occurs due to placenta previa.[ HYPERLINK "" \o "Wikipedia:Citation needed" citation needed]?It has been suggested that incidence of placenta praevia is increasing due to increased rate of Caesarian section.[21]Perinatal mortality rate of placenta praevia is 3-4 times higher than normal pregnancies.[22]HistoryIn places where a Caesarean section could not be performed due to the lack of a surgeon or equipment, infant could be delivered vaginally. There were two ways of doing this with a placenta praevia:The baby's head can be brought down to the placental site (if necessary with?Willet's forceps?or a? HYPERLINK "" \o "Vulsellum" vulsellum) and a weight attached to his scalpA leg can be brought down and the baby's buttocks used to compress the placental siteThe goal of this type of delivery is to save the mother, and both methods will often kill the baby. These methods were used for many years before Caesarean section and saved the lives of both mothers and babies with this condition.Placental abruption?(also known as?abruptio placentae) is a?complication of pregnancy, wherein the?placental?lining has separated from theuterus?of the?mother. It is the most common pathological cause of late pregnancy bleeding. In humans, it refers to the abnormal separation after 20 weeks of gestation and prior to birth. It occurs in 1% of?pregnancies?worldwide. Placental abruption is a significant contributor to maternal mortality worldwide; early and skilled medical intervention is needed to ensure a good outcome, and this is not available in many parts of the world. Treatment depends on how serious the abruption is and how far along the woman is in her pregnancy.[1]Placental abruption has effects on both mother and fetus. The effects on the mother depend primarily on the severity of the abruption, while the effects on the fetus depend on both its severity and the gestational age at which it occurs.[2]?The heart rate of the fetus can be associated with the severity.[3]Lasting effectsOn the mother:A large loss of blood or hemorrhage may require blood transfusions and intensive care after delivery. 'APH?weakens for?PPH?to kill'.The uterus may not contract properly after delivery so the mother may need medication to help her uterus contract.The mother may have problems with blood clotting for a few days.If the mother's blood does not clot (particularly during a?caesarean section) and too many transfusions could put the mother into?disseminated intravascular coagulation?(DIC) due to increased? HYPERLINK "" \o "Thromboplastin" thromboplastin, the doctor may consider a?hysterectomy.A severe case of shock may affect other organs, such as the liver, kidney, and pituitary gland. Diffuse cortical necrosis in the kidney is a serious and often fatal complication.In some cases where the abruption is high up in the uterus, or is slight, there is no bleeding, though extreme pain is felt and reported.On the baby:If a large amount of the placenta separates from the uterus, the baby will probably be in distress until delivery and may die?in utero, thus resulting in a stillbirth.The baby may be premature and need to be placed in the newborn intensive care unit. He or she might have problems with breathing and feeding.If the baby is in distress in the uterus, he or she may have a low level of oxygen in the blood after birth.The newborn may have low blood pressure or a low blood count.If the separation is severe enough, the baby could suffer brain damage or die before or shortly after birth.The newborn may have learning issues at later development stages, often requiring professional pedagogical aid.Symptomscontractions that don't stop (and may follow one another so rapidly as to seem continuous)pain in the uterustenderness in the abdomenvaginal bleeding (sometimes)uterus may be disproportionately enlargedpallorClinical ManifestationClass 0:?asymptomatic. Diagnosis is made retrospectively by finding an organized blood clot or a depressed area on a delivered placenta.Class 1:?mild and represents approximately 48% of all cases. Characteristics include the following:No vaginal bleeding to mild vaginal bleedingSlightly tender uterusNormal maternal BP and heart rateNo?coagulopathyNo? HYPERLINK "" \o "Fetal distress" fetal distressClass 2:?moderate and represents approximately 27% of all cases. Characteristics include the following:No vaginal bleeding to moderate vaginal bleedingModerate-to-severe uterine tenderness with possible tetanic contractionsMaternal tachycardia with orthostatic changes in BP and heart rateFetal distressHypofibrinogenemia (i.e., 50–250?mg/dL)Class 3:?severe and represents approximately 24% of all cases. Characteristics include the following:No vaginal bleeding to heavy vaginal bleedingVery painful tetanic uterusMaternal shockHypofibrinogenemia?(i.e., <150?mg/dL)CoagulopathyFetal deathPathophysiologyTrauma,?hypertension, or?coagulopathy?contributes to the avulsion of the anchoring placental villi from the expanding lower uterine segment, which in turn, leads to bleeding into the?decidua basalis. This can push the placenta away from the uterus and cause further bleeding. Bleeding through the vagina, called overt or external bleeding, occurs 80% of the time, though sometimes the blood will pool behind the placenta, known as concealed or internal placental abruption.Women may present with vaginal bleeding, abdominal or back pain, abnormal or premature contractions,? HYPERLINK "" \o "Fetal distress" fetal distress?or death.Abruptions are classified according to severity in the following manner:Grade 0: Asymptomatic and only diagnosed through post partum examination of the placenta.Grade 1: The mother may have vaginal bleeding with mild uterine tenderness or tetany, but there is no distress of mother or fetus.Grade 2: The mother is symptomatic but not in shock. There is some evidence of fetal distress can be found with fetal heart rate monitoring.Grade 3: Severe bleeding (which may be occult) leads to maternal shock and fetal death. There may be maternal?disseminated intravascular coagulation. Blood may force its way through the uterine wall into the serosa, a condition known as? HYPERLINK "" \o "Couvelaire uterus" Couvelaire uterus.Risk factorsPre-eclampsia?[2]Maternal smoking is associated with up to 90% increased risk.[4]See also:?Smoking and pregnancyMaternal trauma, such as?motor vehicle accidents,?assaults, falls or?nosocomial?infection.Short?umbilical cordProlonged rupture of membranes (>24 hours)Thrombophilia?[2]Retroplacental? HYPERLINK "" \o "Uterine fibroids" fibromyomaMultiparity?[2]Multiple pregnancy[2]Maternal age: pregnant women who are younger than 20 or older than 35 are at greater risk.Previous abruption: Women who have had an abruption in previous pregnancies are at greater risk.Previous Caesarean section[2]some infections are also diagnosed as a causecocaine intoxication[5]PreventionAlthough the risk of placental abruption cannot be eliminated, it can be reduced. Avoiding tobacco, alcohol and cocaine during pregnancy decreases the risk. Staying away from activities which have a high risk of physical trauma is also important. Women who have high blood pressure or who have had a previous placental abruption and want to conceive must be closely supervised by a doctor.[6]The risk of placental abruption can be reduced by maintaining a good?diet?including taking?folic acid, regular?sleep?patterns and correction of?pregnancy-induced hypertension.It is crucial for women to be made aware of the signs of placental abruption, such as vaginal bleeding, and that if they experience such symptoms they must get into contact with their health care provider/the hospital?without any delay.InterventionPlacental abruption is suspected when a pregnant mother has sudden localized abdominal pain with or without bleeding. The?fundus?may be monitored because a rising fundus can indicate bleeding. An ultrasound may be used to rule out?placenta praevia?but is not diagnostic for abruption. The mother may be given? HYPERLINK "" \o "Rhogam" Rhogam?if she is?Rh negative.Treatment depends on the amount of blood loss and the status of the fetus. If the fetus is less than 36 weeks and neither mother or fetus is in any distress, then they may simply be monitored in hospital until a change in condition or fetal maturity whichever comes first.Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother is in distress. Blood volume replacement to maintain blood pressure and?blood plasma?replacement to maintain fibrinogen levels may be needed. Vaginal birth is usually preferred over?caesarean section?unless there is fetal distress. Caesarean section is contraindicated in cases of disseminated intravascular coagulation. Patient should be monitored for 7 days for PPH. Excessive bleeding from uterus may necessitate hysterectomy.PrognosisThe prognosis of this complication depends on whether treatment is received by the patient, on the quality of treatment, and on the severity of the abruption.In the Western world, maternal deaths due to placental abruption are rare; for instance a study done in Finland found that, between 1972 and 2005 placental abruption had a maternal mortality rate of 0.4 per 1,000 cases (which means that 1 in 2,500 women who had placental abruption died); this was similar to other Western countries during that period.[7]?The prognosis on the fetus is worse, currently, in the UK, about 15% of fetuses die following this event.[2]Without any form of medical intervention, as often happens in many parts of the world, placental abruption has a high maternal mortality rate.Chromosome abnormalityA?chromosome anomaly,?abnormality,?aberration, or?mutation?is a missing, extra, or irregular portion of?chromosomal?DNA.[1]?It can be from an atypical number of chromosomes or a structural abnormality in one or more chromosomes. A?karyotype?refers to a full set of chromosomes from an individual which can be compared to a "normal" karyotype for the?species?via?genetic testing. A chromosome anomaly may be detected or confirmed in this manner. Chromosome anomalies usually occur when there is an error in?cell division?following?meiosis?or?mitosis. There are many types of chromosome anomalies. They can be organized into two basic groups, numerical and structural anomaliesNumerical disordersThis is called?aneuploidy?(an abnormal number of chromosomes), and occurs when an individual is missing either a chromosome from a pair (monosomy) or has more than two chromosomes of a pair (trisomy,? HYPERLINK "" \o "Tetrasomy" tetrasomy, etc.).In humans an example of a condition caused by a numerical anomaly is?Down Syndrome, also known as Trisomy 21 (an individual with Down Syndrome has three copies of chromosome 21, rather than two). Trisomy has been determined to be a function of?maternal age.An example of monosomy is?Turner Syndrome, where the individual is born with only one sex chromosome, an X.Structural abnormalitiesWhen the chromosome's structure is altered, this can take several forms:Deletions: A portion of the chromosome is missing or deleted. Known disorders in humans include?Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4; and?Jacobsen syndrome, also called the terminal 11q deletion disorder.Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material. Known human disorders include?Charcot-Marie-Tooth disease type 1A?which may be caused by duplication of the gene encoding?peripheral myelin protein 22?(PMP22) on chromosome 17.Translocations: A portion of one chromosome is transferred to another chromosome. There are two main types of translocations:Reciprocal translocation: Segments from two different chromosomes have been exchanged.Robertsonian translocation: An entire chromosome has attached to another at the centromere - in humans these only occur with chromosomes 13, 14, 15, 21 and 22.Inversions: A portion of the chromosome has broken off, turned upside down and reattached, therefore the genetic material is inverted.Insertions: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome.Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss of genetic material.Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere.Chromosome instability syndromes?are a group of disorders characterized by chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies.InheritanceMost chromosome abnormalities occur as an accident in the egg or sperm, and therefore the anomaly is present in every cell of the body. Some anomalies, however, can happen after conception, resulting in? HYPERLINK "" \o "Mosaicism" Mosaicism?(where some cells have the anomaly and some do not). Chromosome anomalies can be inherited from a parent or be "de novo". This is why chromosome studies are often performed on parents when a child is found to have an anomaly. If the parents do not possess the abnormality it was not initially?inherited; however it may be transmitted to subsequent generations.Cri du chatCri du chat syndrome, also known as?chromosome 5p deletion syndrome,?5p- (said minus) syndrome?or?Lejeune’s syndrome, is a rare genetic disorder due to a missing part (deletion) of?chromosome 5. Its name is a French term (cat-cry?or?call of the cat) referring to the characteristic cat-like?cry?of affected children. It was first described by? HYPERLINK "" \o "Jér?me Lejeune" Jér?me Lejeune?in 1963.[1]?The condition affects an estimated 1 in 50,000 live births, strikes all ethnicities, and is more common in females by a 4:3 ratio.[2]Signs and symptomsThe syndrome gets its name from the characteristic cry of affected infants, which is similar to that of a meowing kitten, due to problems with the larynx and nervous system. About 1/3 of children lose the cry by age 2. Other symptoms of cri du chat syndrome may include:feeding problems because of difficulty swallowing and sucking;low birth weight?and poor growth;severe cognitive, speech, and motor delays;behavioral problems such as hyperactivity, aggression, tantrums, and repetitive movements;unusual facial features which may change over time;excessive?drooling;small head and jaw;wide eyes;skin tags in front of eyes.Other common findings include? HYPERLINK "" \o "Hypotonia" hypotonia,?microcephaly,?growth retardation, a round face with full cheeks,? HYPERLINK "" \o "Hypertelorism" hypertelorism,? HYPERLINK "" \o "Epicanthal folds" epicanthal folds, down-slanting?palpebral fissures,?strabismus, flat nasal bridge, down-turned mouth,? HYPERLINK "" \o "Micrognathia" micrognathia, low-set ears, short fingers,?single palmar creases, and cardiac defects (e.g.,?ventricular septal defect?[VSD],?atrial septal defect?[ASD],?patent ductus arteriosus?[PDA],?tetralogy of Fallot). People with Cri du chat are fertile and can reproduce.It has also been observed that people with the condition have difficulties communicating. While levels of proficiency can range from a few words to short sentences, it is often recommended by medical professionals for the child to undergo some sort of speech therapy/aid with the help of a professional.Less frequently encountered findings include?cleft lip?and palate, preauricular tags and fistulas, thymic dysplasia,?intestinal malrotation,? HYPERLINK "" \o "Megacolon" megacolon,?inguinal hernia,?dislocated hips,cryptorchidism,?hypospadias, rare renal malformations (e.g.,?horseshoe kidneys,?renal ectopia?or agenesis,? HYPERLINK "" \o "Hydronephrosis" hydronephrosis),? HYPERLINK "" \o "Clinodactyly" clinodactyly?of the?fifth fingers,? HYPERLINK "" \o "Talipes equinovarus" talipes equinovarus,? HYPERLINK "" \o "Pes planus" pes planus,syndactyly?of the second and third fingers and toes,? HYPERLINK "" \o "Oligosyndactyly (page does not exist)" oligosyndactyly, and hyperextensible joints. The syndrome may also include various dermatoglyphics, including transverse flexion creases, distal axial triradius, increased whorls and arches on digits, and a?single palmar crease.Late childhood and adolescence findings include significant intellectual disability,?microcephaly, coarsening of facial features, prominent supraorbital ridges, deep-set eyes, hypoplastic nasal bridge, severe?malocclusion, and?scoliosis.Affected females reach puberty, develop secondary sex characteristics, and menstruate at the usual time. The genital tract is usually normal in females except for a report of a? HYPERLINK "" \o "Bicornuate uterus" bicornuate uterus. In males, testes are often small, but spermatogenesis is thought to be normal.GeneticsCri du chat syndrome is due to a partial deletion of the short arm of?chromosome?number 5, also called "5p? HYPERLINK "" \o "Monosomy" monosomy". Approximately 90% of cases result from a sporadic, or randomly occurring,?de novo?deletion. The remaining 10-15% are due to unequal segregation of a parental?balanced translocation?where the 5p monosomy is often accompanied by a trisomic portion of the genome. These individuals may have more severe disease than those with isolated monosomy of 5p. A recent study suggests this may not be the case where a trisomy of chromosome 4q is involved.[3]Most cases involve total loss of the most distant 10-20% of the material on the short arm. Fewer than 10% of cases have other rare cytogenetic aberrations (e.g., interstitial deletions, HYPERLINK "" \o "Mosaicism" mosaicisms, rings and?de novo?translocations). The deleted chromosome 5 is paternal in origin in about 80% of?de novo?cases. Loss of a small region in band 5p15.2 (cri du chat critical region) correlates with all the clinical features of the syndrome with the exception of the catlike cry, which maps to band 5p15.3 (catlike critical region). The results suggest that 2 noncontiguous critical regions contain genes involved in this condition's etiology. Two genes in these regions,? HYPERLINK "" \o "Semaphorine F" Semaphorine F?(SEMA5A) and?delta catenin?(CTNND2), are potentially involved in cerebral development. The deletion of the?telomerase reverse transcriptase?(hTERT) gene localized in 5p15.33 may contribute to the phenotypic changes in cri du chat syndrome as well.Diagnosis and managementDiagnosis is based on the distinctive cry and accompanying physical problems. Seeing as these symptoms are quite easily observable, affected children are typically diagnosed by a doctor or nurse at birth.?Genetic counseling?and?genetic testing?may be offered to families with individuals who have cri du chat syndrome. Prenatally the deletion of the cri du chat related region in the p arm of chromosome 5 can be detected from amniotic fluid or chorionic villi samples with BACs-on-Beads technology.G-banded karyotype of a carrier is also useful.[4]?Children may be treated by speech, sound, and occupational therapists. Cardiac abnormalities often require surgical correction.Down syndromeDown syndrome?(DS) or?Down's syndrome, also known as?trisomy 21, is a?genetic disorder?caused by the presence of all or part of a third copy ofchromosome 21.[1]?It is typically associated with?physical growth?delays, characteristic?facial features?and mild to moderate?intellectual disability.[2]The average?IQ?of a young adult with Down syndrome is around 50, similar to the mental age of an 8 or 9?year old child.[3]Down syndrome can be identified during pregnancy by?prenatal screening?or after birth by direct observation and genetic testing. Since the introduction of screening, pregnancies with the diagnosis are often?terminated.[4][5]?Regular screening for health problems common in Down syndrome is recommended throughout the person's life.Education and proper care has been shown to improve?quality of life.[6]?Some children with Down syndrome are educated in regular school classes while others require more specialized education.[7]?Some children with Down syndrome graduate from high school and in adulthood some individuals work in the community.[8]?The degree of independence possible for an affected individual varies, and some require a more sheltered work environment.[7]?Support in financial and legal matters is often needed.[9]?Life expectancy is around 50 to 60?years in the developed world with proper health care.[3][9]Down syndrome is the most common?chromosome abnormality?in humans HYPERLINK "" \l "cite_note-Malt2013-3" [3]?occurring in about 1 per 1000 babies born each year.[2]?It is named afterJohn Langdon Down, the British doctor who fully described the syndrome in 1866.[10]?Some aspects of the condition were described earlier by?Jean-?tienne Dominique Esquirol?in 1838 and? HYPERLINK "" \o "?douard Séguin" ?douard Séguin?in 1844.[11]?The genetic cause of Down syndrome, an extra copy of chromosome 21, was identified by Dr.? HYPERLINK "" \o "Jér?me Lejeune" Jér?me Lejeune?in 1959.[10]Signs and symptomsA drawing of the facial features of Down syndromeThose with Down syndrome nearly always have physical and mental disabilities.[12]?As adults their mental abilities are typically similar to that of an 8 or 9 year old.[3]?They also typically have?poor immune function[13]?and?developmental milestones?generally are reached at a later age.[9]?There is an increased risk of a number of other health problems including:?congenital heart disease,? HYPERLINK "" \o "Leukemia" leukemia,?thyroid disorders, and?mental illness, among others.[10]CharacteristicsPercentageCharacteristicsPercentageStunted growth90%[14]Flattened nose68%[13]Mental impairment99%[15]Abnormal teeth60%[16]Increased skin back of neck80%[10]Bent fifth finger tip57%[13]Separation of 1st and 2nd toes68%[16]Umbilical hernia90%[17]Flexible ligaments75%[13]Short neck60%[16]Low muscle tone80%[18]Shortened hands60%[16]Flat head75%[13]Congenital heart disease40%[16]Undescended testicles20%[19]Single transverse palmar crease53%[13]Eyelid fold60%[16]Protruding tongue47%[16]Shortened arms and legs70%Epicanthic fold59%[13]Narrow?roof of mouth76%[16]Strabismus~35%[2]Abnormal?outer ears70%[10]Brushfield spots?in the?iris56%[13]PhysicalFeet of a boy with Down SyndromeThey may have some or all of the following physical characteristics:?abnormally small chin, slanted eyes,?poor muscle tone, a flat?nasal bridge, a?single crease of the palm, a protruding tongue due to small mouth, and an?enlarged tongue.[18]?Other common features include: a flat and wide face,[18]?there is a short neck, excessive joint flexibility, extra space between?big toe?and second toe, an abnormal?patterns on the fingertops?and short fingers.[16][18]Instability of the? HYPERLINK "" \o "Atlanto-axial joint" atlanto-axial joint?occurs in approximately 20% and may lead to?spinal cord injury?in 1-2%.[3][9]?Around half of those with DS haveobstructive sleep apnea.[10]?Hip dislocations occur without trauma in an up to a third.[10]Growth in height is slower resulting in adults tending to have?short stature—the average height for men is 154?cm (5 feet 1?inch) and for women is 142?cm (4 feet 8?inches).[20]?Individuals with DS are at increased risk for obesity as they age.[10]?There are?growth charts?specifically for those with Down syndrome.[10]NeurologicalMost individuals with Down syndrome have mild (IQ: 50–70) or moderate?intellectual disability?(IQ: 35–50) with some cases having severe (IQ: 20–35) difficulties.[2][21]?As they age they typically perform less well compared to their same aged peers.[21][22]?Some after 30?years of age may lose their ability to speak.[3]?Those with?mosaic?Down syndrome typically have scores 10–30 points higher.[23]?This syndrome causes about a third of cases of intellectual disability.[13]Fine motor skills[24]?and?large scale motor skills?are often delayed which can interfere with cognitive development. Effects of the condition gross motor skills is variable. Some children will begin walking at around 2 years of age, while others will not walk until age monly individuals with Down syndrome have some difficulty speaking with better language understanding.[10][21]?10 to 45% have either?stuttering?or?rapid and irregular speech?making them difficult to understand.[25]?They typically do fairly well with social skills.[10]?Behavior problems are not generally as great as an issue as in other syndromes associated with intellectual disability.[21]?In children with Down syndrome?mental illness?occurs in nearly 30% with?autism?occurring in 5-10%.[9]?While generally happy, symptoms of?depression?and?anxiety?may develop in early adulthood.[3]Children and adults with DS are at increased risk of?epileptic seizures?which occur in 5-10% of children and up to 50% of adults.[3]?This includes an increased risk of a specific type of seizure called?infantile spasms.[10]?Many (15%) who live past 40s develop dementia of the?Alzheimer's disease?type.[26]?Of those who reach 60?years, 50-70% have the disease.[3]SensesBrushfield spots, visible in the irises of a baby with Down Syndrome.Hearing and vision disorders occur in more than half of people with DS.[10]?Vision problems occur in 38 to 80%.[2]?Between 20 and 50% have?strabismus, in which the two eyes do not move in tandem. HYPERLINK "" \l "cite_note-Wei2010-2" [2]?Refractive errors?requiring glasses or contacts are also common.[3]?Cataracts?(opacity of the lens) occur in 15%, HYPERLINK "" \l "cite_note-Nelson2011-9" [9]?and may be present at birth.[2]? HYPERLINK "" \o "Keratoconus" Keratoconus?(thin, cone-shaped corneas), HYPERLINK "" \l "cite_note-Malt2013-3" [3]?and?glaucoma?(increased eye pressures) are also more common.[2]? HYPERLINK "" \o "Brushfield spots" Brushfield spots?(small white or grayish/brown spots on the periphery of the?iris) are present in 38 to 85%.[2]Hearing problems are found in 38-78% of children with Down syndrome compared to 2.5% of normal children.[2]?Diagnosis and aggressive treatment of chronic ear disease (e.g. HYPERLINK "" \o "Otitis media" otitis media) in children with Down syndrome can bring many of the children up to normal hearing levels.[27]?Age related hearing loss of the? HYPERLINK "" \o "Sensorineural hearing loss" sensorineural type?occurs at a much earlier age affected 10-70%.[3]Otitis media with effusion?is the most common cause of hearing loss in children with Down's occurring in 50-70%.[9]?Ear infections often start at birth and continue throughout the children's life.[28]The ear infections are mainly due to poor? HYPERLINK "" \o "Eustachian tube" eustachian tube?function.[29]?However, excessive wax can also cause obstruction of the outer ear canal and hearing problems.[3]?Middle ear problems account for 83% of hearing loss in children with Down syndrome.[30]?The degree of hearing loss varies but even a mild degree can have major consequences for speech understanding, language learning, and academics HYPERLINK "" \l "cite_note-Wei2010-2" [2]?if not detected in time and corrected.[31]?It is important to rule out hearing loss as a contributing factor in social and mental deterioration.[32]HeartThe rate of?congenital heart disease?in newborns with Down syndrome is around 40%.[16]?An? HYPERLINK "" \o "Atrioventricular septal defect" atrioventricular septal defect?also known as? HYPERLINK "" \o "Endocardial cushion" endocardial cushion?defect is the most common form with up to 40% affected. This is closely followed by?ventricular septal defect?that affects approximately 35%.[33]?Mitral valve?problems become common as people age, even in those without heart problems at birth.[3]?Other problems that may occur include:?tetralogy of Fallot?and?patent ductus arteriosus.[29]?People with Down syndrome have a lower risk of?hardening of the arteries.[3]CancerAlthough the general incidence of cancer amongst individuals with Down syndrome is the same as in the general population,[34]?there is a reduced risk of solid cancers and an increased risk of leukemia and testicular cancer.[3]?Solid cancers are believed to be less common due to the? HYPERLINK "" \o "Tumor suppressor gene" tumor suppressor genes?present on chromosome 21.[35]Cancers of the blood?are 10 to 15 times more common in children with DS.[10]?In particular,?acute lymphoblastic leukemia?is 20 times more common and the? HYPERLINK "" \o "Megakaryoblastic" megakaryoblastic?form of?acute myelogenous leukemia?is 500 times more common.[36]?Transient? HYPERLINK "" \o "Myeloproliferative disease" myeloproliferative disease, a disorder of blood cell production that does not occur outside of Down syndrome, affects 3-10% of infants.[36][37]?The disorder is typically not serious but occasionally can be.[37]?It resolves most times without treatment; however, in those who have had it there is a 20 to 30 percent risk of developing acute lymphoblastic leukemia at a latter time.[37]EndocrineProblems of the?thyroid gland?occur in 20-50%.[3][10]?Low thyroid?is the most common, occurring in almost half of those with DS.[3]?Thyroid problems can be due to a poorly or non functioning thyroid at birth (known as?congenital hypothyroidism) which occurs in 1%[9]?or can develop latter due to an attack on the thyroid by the?immune system?resulting in? HYPERLINK "" \o "Graves disease" Graves disease?or?autoimmune hypothyroidism.[38]?Type 1 diabetes mellitus?is also more common.[3]GastrointestinalConstipation occurs in nearly half of people with DS and may result in changes in behavior.[10]?One potential cause is? HYPERLINK "" \o "Hirschsprung's disease" Hirschsprung's disease, which is due to a lack of nerve cells controlling thecolon, which occurs in 2 to 15%.[39]?Other frequent congenital problems include:?duodenal atresia,?pyloric stenosis,? HYPERLINK "" \o "Meckel diverticulum" Meckel diverticulum?and?imperforate anus.[29]?Celiac disease?affects about 7-20%[3][10]?and? HYPERLINK "" \o "Gastroesophageal reflux disease" gastroesophageal reflux disease?is also more common.[29]FertilityMales with Down syndrome usually do not father children, while females have lower rates of fertility relative those who are unaffected.[40]?Fertility is estimated to be present in 30-50% of women HYPERLINK "" \l "cite_note-Nel2010-41" [41]?and they often have difficulties with?miscarriages,?premature births, and? HYPERLINK "" \o "Childbirth" labor.?Menopause?typically occurs at an earlier age.[3]?The poor fertility in men is thought to be due to problems with?sperm development; however, it may also be related to not being sexually active.[40]?As of 2006 there have been three recorded instances of males with DS fathering children and 26 cases of women having children.[40]?Without?assisted reproductive technologies, approximately half of the pregnancies of someone with Down syndrome will also have the syndrome.[40][42]GeneticsMain article:?Genetics of Down syndromeDown syndrome is caused by having three copies of the?genes?on?chromosome 21, rather than the usual two.[1][43]?The parents of the affected individual are typically genetically normal.[13]?Those who have one child with Down syndrome have about a 1% risk of having a second child with the syndrome, if both parents are found to have normal karyotypes.[41]The extra chromosome content can arise through several different mechanisms. The most common cause (approximately 92-95% of cases) is a complete extra copy of chromosome 21, resulting in?trisomy?21.[42][44]?In 1 to 2.5%, some of the cells in the body are normal and others have trisomy 21, known as?mosaic?Down syndrome.[41][45]?The other common mechanisms that can give rise to Down syndrome include? HYPERLINK "" \o "Robertsonian translocation" Robertsonian translocation,? HYPERLINK "" \o "Isochromosome" isochromosomes,?ring chromosomee, which contain additional material from chromosome 21. These findings occurs in approximately 2.5% of cases.[10][41]?Isochromosomes result when the two long arms separate together on one chromosome.[42]Trisomy 21Karyotype?for trisomy Down syndrome. Notice the three copies of chromosome 21Trisomy 21 (also known by the?karyotype?47,XX,+21 for males and 47,XY,+21 for females)[46]?is caused by a failure of the chromosomes to separate during?egg or sperm development.[42]?As a result, a sperm or egg cell is produced with an extra copy of chromosome 21; this cell thus has 24 chromosomes. When combined with a normal cell from the other parent, the?embryo?and baby has 47 chromosomes, with three copies of chromosome 21. Trisomy 21 is the cause of approximately 92 to 95% of cases of Down syndrome, HYPERLINK "" \l "cite_note-Patt2009-1" [1][42]?with 88% of cases resulting from non separation of the chromosomes in the mother and 8% coming from non separation in the father.[47]TranslocationThe extra chromosome 21 material may also occur due to a? HYPERLINK "" \o "Robertsonian translocation" Robertsonian translocation?in 2-4% cases.[41][48]?This may be a new mutation or previously present in one of the parents.[49]?In this case, the long arm of chromosome 21 is attached to another chromosome, often?chromosome 14?known as 45XY,t(14q21q) in males.[50][51]?The risk of this type of Down syndrome is not related to the mothers age.[50]?The parent with such a translocation is usually normal physically and mentally; HYPERLINK "" \l "cite_note-Mich2013-50" [50]?however, during production of egg or sperm cells there is a higher chance of creating reproductive cells with extra chromosome 21 material.[48]?This results in a 15% chance of having a child with DS when the mother is affected and a less than 5% risk if the father is affected.[49]?Additionally some children may inherit this translocation while not have DS but are subsequently at higher risk of having children with DS themselves.[50]?In this case it is sometimes known as familial Down syndrome.[52]MechanismIn general, extra chromosome 21 DNA leads to an over-expression of certain genes.[43]?This over expression is about 50%.[41]?It is estimated that chromosome 21 contains around 310 genes.[43]Some research has shown that the parts of the chromosome which are of greatest importance are bands 21q22.1-q22.3.[53]?This area includes genes for amyloid,?superoxide dismutase, and likely the?ETS-2 proto oncogene.[54]?Other research has not confirmed these findings.[43]The dementia which occurs in Down syndrome is due to too much?amyloid beta peptides?being produced in the brain.[55]?Senile plaques?and?neurofibrillary tangles?are present in nearly all by 35?years of age even though dementia may not be present.[13]?Those with DS lack a normal number of?lymphocytes?and produce less?antibodies?which contributes to there increased risk of infection.[10]ScreeningGuidelines recommend that screening for Down syndrome be offered to all pregnant women, regardless of age.[56][57]?A number of tests can be used, with varying levels of accuracy. They are usually used in combination to increase their detection rate, while maintaining a low false positive rate, but are not definitive.[10]?If screening is positive either?amniocentesis?or?chorionic villous sampling?is required to confirm the diagnosis.[56]?Screening in both the first and second trimesters is better than just screening in the first trimester.[56]?The different screening techniques in use are able to pick up 90 to 95% of cases with a false positive rate of between 2 and 5%.[58]UltrasoundUltrasound of fetus with Down syndrome showing a?large bladderEnlarged NT and absent nasal bone in a fetus at 11 weeks with Down syndromeUltrasound imaging can be used to screen for Down syndrome. Finding that increase the risk, when seen at 14 to 24 weeks of?gestation?include: a small or no nasal bone,?large ventricles, nuchal fold thickness, and an abnormal right?subclavian artery?among others.[59]?The presence or absence of many markers is more accurate.[59]Increased fetal?nuchal translucency?(NT) indicates an increased risk of Down syndrome picking up 75-80% of cases and being falsely positive in 6%.[60]Blood testsSeveral blood markers can be measured that to predict the risk of Down syndrome during the second trimester.[61]?Often two or three or used in combination with two or three of:?α-fetoprotein, unconjugated estriol, total hCG, and free βhCG detecting about 60-70% of cases.[61]?First trimester screening with markers is not as accurate and thus is not generally recommended by itself.[62]Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester.[63][64]?The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at a high risk for trisomy 21.[65]?Accuracy has been reported at 98.6% in the first trimester of pregnancy.[10]?Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.[65]DiagnosisBefore birthWhen screening tests predict a high risk of Down syndrome, a more invasive diagnostic test (amniocentesis?or?chorionic villus sampling) is needed to confirm the diagnosis.[56]?If Down syndrome occurs in 1 in 500 pregnancies and the test used has a 5% false positive rate, this means that of 28 women who test positive on screening only 1 will have Down syndrome confirmed.[58]?If the screening test has a 2% false positive rate this improves to 1 out of 10 who test positive on screening having a fetus with DS.[58]?Amniocentesis and chorionic villus sampling are more reliable; however, carry an increased risk of miscarriage of between 0.5 and 1%.[66]?There is also an increased risk of limb problems in the offspring due to the procedure.[66]?The risk from the procedure is greater the earlier it is preformed and thus amniocentesis is not recommended before 15?weeks gestational age and chorionic villus sampling before 10?weeks gestational age.[66]Abortion ratesAbout 92% of pregnancies in the United Kingdom and Europe with a diagnosis of Down syndrome are terminated.[5]?In the United States termination rates are around 67%; however this varies significantly depending upon the population looked at.[4]When non pregnant people are asked if they would have a termination if their fetus tested positive 23-33% said yes, when high risk pregnant women were asked 46-86% said yes, and when women who screen positive are asked 89-97% say yes.[67]After birthThe diagnosis can typically be made based on the appearance of the child at birth.[9]?An analysis of the child's chromosomes is recommended to confirm the diagnosis and determine if a translocation is present as if it this may help determine the risk of the child's parents having further children with DS.[9]?Parents generally wish to know the possible diagnosis once it is suspected and do not wish pity.[10]ManagementEfforts such as?early childhood intervention, screening for common problems, medical treatment where indicated, a good family environment, and work related training can improve the development of children with Down syndrome. Education and proper care can improve?quality of life.[6]?Typical?vaccinations?are recommended.[10]Health screeningRecommended screeningTestingChildren[68]Adults[3]Hearing6 months, 12 months, then yearly3–5 yearsT4?and?TSH6 months, then yearlyEyes6 months, then yearly3–5 yearsTeeth2 years, then every 6 months.Coeliac diseaseBetween 2 and 3 years of age,or earlier if symptoms occur.Sleep study3 to 4 years, or earlier if symptomsof?obstructive sleep apnea?occur.Neck X-raysBetween 3 and 5 years of ageA number of health organizations, have issued recommendations for?screening?those with Down syndrome for particular diseases.[68]?It is recommended that this be done systematically.[10]At birth all children should get an?electrocardiogram?and?ultrasound of the heart.[10]?Surgical repair of heart problems may be required around three months of age.[10]?Heart valve?problems may occur in young adults and further ultrasound evaluation may be needed when in adolescents and early adulthood.[10]?Due to the elevated risk of testicular cancer some recommend checking the person's testicles yearly.[3]Cognitive developmentHearing aids?or other amplification devices can be useful for language learning in those with hearing loss of any degree.[10]?Early communication intervention help language skills. Language assessments can help determine strengths and weaknesses; for example, it is common for understanding to exceed expressive skills. As those with Down's typically have good hand eye coordination, learning?sign language?may be possible.[21]Speech therapy?may be useful and it is recommended that it be started around 9 months of age.[10]?Augmentative and alternative communication?methods, such as pointing, body language, objects, or graphics are often used to aid communication. Relatively little research has focused on the effectiveness of communications intervention strategies.[69]Education programs before reaching school age may be useful.[2]?When of school age children with Down syndrome may benefit from?mainstreaming?(whereby students of differing abilities are placed in classes with their chronological peers) provided that some adjustments are made to the curriculum.[70]?Evidence to support this however is not very strong.[71]?In the United States theIndividuals with Disabilities Education Act?of 1975 requires that public school generally allow attendance by students with Down's.[72]Behavioral issues and mental illness are typically managed with counselling and or medications.[9]MedicationsEfforts to prevent?respiratory syncytial virus?(RSV) with?human monoclonal antibodies?should be considered, especially in those with heart problems.[2]?In those who develop dementia there is no evidence for?memantine,[73]?donepezil,[74]?rivastigmine,[75]?or?galantamine.[76]Edwards syndrome?(also known as?Trisomy 18?[T18]) is a?genetic disorder?caused by the presence of all or part of an extra?18th chromosome. This genetic condition almost always results from?nondisjunction?during?meiosis. It is named after?John Hilton Edwards, who first described the syndrome in 1960.[1]?It is the second most common?autosomal?trisomy, after?Down syndrome, that carries to term.Edwards syndrome occurs in around one in 6,000 live births and around 80 percent of those affected are female.[2]?The majority of fetuses with the syndrome die before birth.[2]?The incidence increases as the?mother's age increases. The syndrome has a very low rate of survival, resulting from heart abnormalities, kidney malformations, and other internal organ disorders.Signs and symptomsChildren born with Edwards syndrome may have some or all of the following characteristics: kidney malformations, structural heart defects at birth (i.e.,?ventricular septal defect,?atrial septal defect,?patent ductus arteriosus), intestines protruding outside the body ( HYPERLINK "" \o "Omphalocele" omphalocele),? HYPERLINK "" \o "Esophageal atresia" esophageal atresia,?intellectual disability, developmental delays, growth deficiency,?feeding difficulties,breathing difficulties, and? HYPERLINK "" \o "Arthrogryposis" arthrogryposis?(a muscle disorder that causes multiple joint contractures at birth).[3][4]Some physical malformations associated with Edwards syndrome include small head (microcephaly) accompanied by a prominent back portion of the head (occiput); low-set, malformed ears; abnormally small jaw ( HYPERLINK "" \o "Micrognathia" micrognathia);?cleft lip/cleft palate; upturned nose; narrow eyelid folds (palpebral fissures); widely spaced eyes (ocular hypertelorism); drooping of the upper eyelids (ptosis); a short breast bone; clenched hands; choroid plexus cysts; underdeveloped thumbs and or nails,?absent radius,?webbing?of the second and third?toes;?clubfoot?or?Rocker bottom feet; and inmales,?undescended testicles.[3][4]Clenched hand and overlapping fingers: index finger overlaps third finger and fifth finger overlaps fourth finger, characteristically seen in Trisomy 18.In utero, the most common characteristic is cardiac anomalies, followed by central nervous system anomalies such as head shape abnormalities. The most common intracranial anomaly is the presence of?choroid plexus cysts, which are pockets of fluid on the brain. These are not problematic in themselves, but their presence may be a marker for trisomy 18.[5][6]?Sometimes excess?amniotic fluid?or? HYPERLINK "" \o "Polyhydramnios" polyhydramnios?is exhibited.[3]GeneticsEdwards syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the?18th chromosome, either in whole (trisomy?18) or in part (such as due to?translocations). The additional chromosome usually occurs before?conception. The effects of the extra copy vary greatly, depending on the extent of the extra copy, genetic history, and chance. Edwards syndrome occurs in all human populations but is more prevalent in female offspring.[7]A healthy egg and/or sperm cell contains individual chromosomes, each of which contributes to the 23 pairs of chromosomes needed to form a normal cell with a typical human?karyotype?of 46 chromosomes. Numerical errors can arise at either of the two?meiotic?divisions and cause the failure of a chromosome to segregate into the daughter cells (nondisjunction). This results in an extra chromosome, making the?haploid?number 24 rather than 23. Fertilization of eggs or insemination by sperm that contain an extra chromosome results in trisomy, or three copies of a chromosome rather than two.[8]Trisomy 18 (47,XX,+18) is caused by a?meiotic?nondisjunction?event. With?nondisjunction, a?gamete?(i.e., a sperm or egg cell) is produced with an extra copy of chromosome 18; the gamete thus has 24 chromosomes. When combined with a normal gamete from the other parent, the?embryo?has 47 chromosomes, with three copies of chromosome 18.A small percentage of cases occur when only some of the body's cells have an extra copy of chromosome 18, resulting in a mixed population of cells with a differing number of chromosomes. Such cases are sometimes called?mosaic?Edwards syndrome. Very rarely, a piece of chromosome 18 becomes attached to another chromosome ( HYPERLINK "" \o "Chromosomal translocation" translocated) before or after conception. Affected individuals have two copies of chromosome 18 plus extra material from chromosome 18 attached to another chromosome. With a translocation, a person has a partial trisomy for chromosome 18, and the abnormalities are often less severe than for the typical Edwards syndrome.PrognosisIn 2008/2009, there were 495 diagnoses of Edwards syndrome (trisomy 18) in?England?and?Wales, 92% of which were made?prenatally. There were 339?abortions, 49?stillbirths/miscarriages/ HYPERLINK "" \o "Perinatal mortality" fetal deaths, 72 unknown outcomes, and 35 live births.[9]?Because approximately 3% of cases with unknown outcomes are likely to result in a live birth, the total number of live births is estimated to be 37 (2008/09 data are provisional). Major causes of death include? HYPERLINK "" \o "Apnea" apnea?and heart abnormalities. It is impossible to predict an exact?prognosis?during?pregnancy?or the?neonatal period.[7]?Half of infants with this condition do not survive beyond the first week of life.[10]?The?median?lifespan is 5–15 days.[11][12]?About 8% of infants survive longer than 1 year.[13]?One percent of children live to age 10, typically in less severe cases of the?mosaic?Edwards syndrome.[7]?Parents with surviving children who take part in support groups report that these children enriched their family and their couple irrespective of the length of their lives.[14]EpidemiologyEdwards syndrome occurs in approximately 1 in 6,000 live births, but more conceptions are affected by the syndrome because the majority of those diagnosed with the condition prenatally will not survive the prenatal period.[2][15]?Although women in their 20s and early 30s may conceive babies with Edwards syndrome, the risk of conceiving a child with Edwards syndrome increases with a woman's age. The average maternal age for conceiving a child with this disorder is 32?.[16]Patau syndromePatau syndrome?/?p?ta?/?is a?syndrome?caused by a?chromosomal?abnormality, in which some or all of the?cells?of the body contain extra genetic material from?chromosome 13. This can occur either because each cell contains a full extra copy of chromosome 13 (a disorder known as?trisomy 13or?trisomy D), or because each cell contains an extra partial copy of the chromosome (i.e.,? HYPERLINK "" \o "Robertsonian translocation" Robertsonian translocation) or because of?mosaic?Patau syndrome. Full trisomy 13 is caused by?nondisjunction?of chromosomes during?meiosis?(the mosaic form is caused by nondisjunction during?mitosis). The extra genetic material from chromosome 13 disrupts the normal course of development, causing multiple and complex organ defects. Like allnondisjunction?conditions (such as?Down syndrome?and?Edwards syndrome), the risk of this syndrome in the offspring increases with maternal age at pregnancy, with about 31 years being the average.[1]?Patau syndrome affects somewhere between 1 in 10,000 and 1 in 21,700 live births.[2]CausesPatau's syndrome is the result of?trisomy?13, meaning each cell in the body has three copies of chromosome 13 instead of the usual two. A small percentage of cases occur when only some of the body's cells have an extra copy; such cases are called mosaic Patau.Patau syndrome can also occur when part of chromosome 13 becomes attached to another chromosome (translocated) before or at conception in aRobertsonian translocation. Affected people have two copies of chromosome 13, plus extra material from chromosome 13 attached to another chromosome. With a translocation, the person has a partial trisomy for chromosome 13 and often the physical signs of the syndrome differ from the typical Patau syndrome.Most cases of Patau syndrome are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called?non-disjunction?can result in reproductive cells with an abnormal number of chromosomes. For example, an?egg?or?sperm?cell may gain an extra copy of the chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra chromosome 13 in each of the body's cells.?Mosaic?Patau syndrome is also not inherited. It occurs as a random error during cell division early in? HYPERLINK "" \o "Fetal" fetal?development.Patau syndrome due to a translocation can be inherited. An unaffected person can carry a rearrangement of genetic material between chromosome 13 and another chromosome. This rearrangement is called a balanced translocation because there is no extra material from chromosome 13. Although they do not have signs of Patau syndrome, people who carry this type of balanced translocation are at an increased risk of having children with the condition.Manifestations and physical findingsA 37 2/7 week gestational age male infant with Patau syndrome demonstratingpolydactylyOf those fetuses that do survive to gestation and subsequent birth, common abnormalities may include:Nervous systemIntellectual disability?and?motor disorderMicrocephalyHoloprosencephaly?(failure of the forebrain to divide properly).Structural eye defects, including? HYPERLINK "" \o "Microphthalmia" microphthalmia,?Peters anomaly?(a type of eye abnormality),?cataract, iris and/or fundus ( HYPERLINK "" \o "Coloboma" coloboma), retinal dysplasia or?retinal detachment, sensory? HYPERLINK "" \o "Pathologic nystagmus" nystagmus,?cortical visual loss, and?optic nerve hypoplasiaMeningomyelocele?(a?spinal?defect)Musculoskeletal and cutaneousPolydactyly?(extra digits)CyclopiaProboscisLow-set ears[3]Prominent heelDeformed feet known as?rocker-bottom feetOmphalocele?(abdominal?defect)Abnormal?palm?patternOverlapping of fingers over?thumbCutis aplasia?(missing portion of the skin/hair)Cleft palateUrogenitalAbnormal?genitaliaKidney defectsOtherHeart defects?(ventricular septal defect) (Patent Ductus Arteriosus)DextrocardiaSingle umbilical artery[4]DiagnosisDiagnosis is usually based on clinical findings, although fetal chromosome testing will show trisomy 13. While many of the physical findings are similar to Edward's syndrome there are a few unique traits, such as polydactyly. However, unlike Edward's syndrome and Down syndrome, the quad screen does not provide a reliable means of screening for this disorder. This is due to the variability of the results seen in fetuses with Patau.[5]Treatment[ HYPERLINK "" \o "Edit section: Treatment" edit]Medical management of children with Trisomy 13 is planned on a case-by-case basis and depends on the individual circumstances of the patient. Treatment of Patau syndrome focuses on the particular physical problems with which each child is born. Many infants have difficulty surviving the first few days or weeks due to severe neurological problems or complex?heart defects. Surgery may be necessary to repair heart defects or?cleft lip?and?cleft palate. Physical, occupational, and speech therapy will help individuals with Patau syndrome reach their full developmental potential. Surviving children are described as happy and parents report that they enrich their lives.[9]?The cited study grouped?Edwards syndrome, which is sometimes survivable beyond toddlerhood, along with Patau, hence the median age of 4 at the time of data collection.PrognosisMore than 80% of children with Patau syndrome die within the first year of life.[10]Trisomy 8Trisomy 8, also known as?Warkany syndrome 2,[1]?is a human?chromosomal disorder?caused by having three copies (trisomy) of?chromosome?8. It can appear with or without? HYPERLINK "" \o "Mosaicism" mosaicism.CharacteristicsComplete trisomy 8?causes severe effects on the developing fetus and can be a cause of?miscarriage.[2]?Complete trisomy 8 is usually an early lethal condition, whereas?trisomy 8? HYPERLINK "(genetics)" \o "Mosaic (genetics)" mosaicism?is less severe and individuals with a low proportion of affected cells may exhibit a comparatively mild range of physical abnormalities and developmental delay.[3][4]?Individuals with trisomy 8 mosaicism are more likely to survive into childhood and adulthood, and exhibit a characteristic and recognizable pattern of developmental abnormalities. Common findings include retarded psychomotor development, moderate to severe mental retardation, variable growth patterns which can result in either abnormally short or tall stature, an expressionless face, and many musculoskeletal, visceral, and eye abnormalities, as well as other?anomalies.[5]?A deep plantar furrow is considered to be pathognomonic of this condition, especially when seen in combination with other associated features.[6]?The type and severity of symptoms are dependent upon the location and proportion of trisomy 8 cells compared to normal cells.Other conditionsTrisomy 8 mosaicism affects wide areas of chromosome 8 containing many genes, and can thus be associated with a range of symptoms.Mosaic trisomy 8 has been reported in rare cases of? HYPERLINK "" \o "Rothmund-Thomson syndrome" Rothmund-Thomson syndrome, a genetic disorder associated with the?DNA helicase?RECQL4?on chromosome 8q24.3. The syndrome is "characterized by?skin atrophy,?telangiectasia,?hyper-?and?hypopigmentation,?congenital skeletal abnormalities, short?stature,?premature aging, and increased risk of?malignant disease".[7]Some individuals trisomic for chromosome 8 were deficient in production of?coagulation factor VII?due to a factor 7 regulation gene (F7R) mapped to 8p23.3-p23.1.[8]Trisomy and other rearrangements of chromosome 8 have also been found in? HYPERLINK "" \o "Tricho–rhino–phalangeal syndrome" tricho–rhino–phalangeal syndrome.[9]Small regions of chromosome 8 trisomy and monosomy are also created by?recombinant chromosome 8 syndrome?(San Luis Valley syndrome), causing anomalies associated with?tetralogy of Fallot, which results from recombination between a typical chromosome 8 and one carrying a parental paracentric inversion.[10]Trisomy is also found in some cases of?chronic myeloid leukaemia, potentially as a result of karyotypic instability caused by the? HYPERLINK "" \o "Bcr:abl" bcr:abl?fusion gene.Trisomy 22From Wikipedia, the free encyclopediaTrisomy 22?is a?chromosomal disorder?in which there are three copies of?chromosome 22?rather than two. It is a frequent cause of?spontaneous abortion?during the first trimester of?pregnancy. Progression to the second trimester and livebirth are rare. This disorder is found in individuals with an extra copy or a variation of chromosome 22 in some or all cells of their body. There are many kinds of disorders associated with Trisomy 22:Emanuel Syndrome?[1]?is named after the genetic contributions made by researcher Dr. Beverly Emanuel. This condition is assigned to individuals born with an unbalanced 11/22?translocation. That is, when a fragment of chromosome 11 is moved, or translocated to chromosome 22.22q11 Deletion Syndrome?[2]?is a rare condition which occurs in approximately 1 in 4000 births. This condition is identified when a band in the q11.2 section of the arm of chromosome 22 is missing or deleted. This condition has several different names, The 22q11.2 Deletion Sydrome, Velocardiofacial syndrome, DiGeorge Syndrome, Conotruncal Anomaly Face syndrome, Opitz G/BBB Syndrome, Cayler Cardiofacial Syndrome.The effects of this disorder are different in each individual but similarities exist such as heart defects, immune system problems, a distinctive facial appearance, learning challenges, cleft palate, hearing loss, kidney problems, hypocalcemia, and sometimes psychiatric issues.22q11 microduplication syndrome HYPERLINK "" \l "cite_note-3" [3]?is the opposite of the 22q11 deletion syndrome, in this condition, a band of q.11.2 section of chromosome 22 is duplicated. Individuals carrying this deficiency are relatively “normal” as in they don’t possess any major birth defects or major medical illnesses. This microduplication is more common than the deletion; this might be due to the milder phenotype of the individuals.Phelan-McDermid Syndrome / 22q13 Deletion Syndrome HYPERLINK "" \l "cite_note-4" [4]?is a condition caused by the deletion of the tip of the q arm on chromosome 22. Most individuals with this disorder experience cognitive delays as well as low muscle tone and sleeping, eating and behavioural issues.Chromosome Ring 22[5]?is a rare disorder caused by the break and re-join of both ends of chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on the amount of genetic information lost during the break/re-join. Major characteristics for this disorder are mental retardation, muscle weakness and lack of coordination.Cat Eye Syndrome / Schmid Fraccaro Syndrome HYPERLINK "" \l "cite_note-6" [6]?is a condition caused by a partial trisomy or tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found three or four times. This syndrome is referred as “Cat Eye” due to the eye appearance of reported affected individuals who have? HYPERLINK "" \o "Coloboma" coloboma?of the iris?; however, this feature is only seen in about half of the cases.Mosaic trisomy 22[7]?is a disorder in which an extra chromosome 22 is found only in some cells of the body. The severity of each case is determined by the number of cells with this extra copy. Some characteristics of individuals with this condition are cardiac abnormalities, growth retardation, mental delay, etc..Complete Trisomy 22[8]?is in contrast with Mosaic trisomy 22; this disorder is characterized by an extra copy of chromosome 22 which is found in each cell of the body of the affected individual. These cases are very rare, and most of the affected individuals die before birth or shortly after.Klinefelter syndromeKlinefelter syndromeClassification and external resources47,XXYKlinefelter syndrome?or?Klinefelter's syndrome?is the set of symptoms resulting from additional X genetic material in males. Also known as47,XXY?or?XXY, Klinefelter syndrome is a?genetic disorder?in which there is at least one extra?X chromosome?to a standard human male?karyotype, for a total of 47?chromosomes?rather than the 46 found in genetically typical humans.[1]?While females have an XX chromosomal makeup, and males an XY, individuals with Klinefelter syndrome have at least two X chromosomes and at least one?Y chromosome.[2]?Because of the?extra chromosome, individuals with the condition are usually referred to as "XXY males", or "47,XXY males".[3]This chromosome constitution (karyotype) exists in roughly between 1:500 to 1:1000 live male births HYPERLINK "" \l "cite_note-NICHD-4" [4][5][note 1]?but many of these people may not show symptoms. If the physical traits associated with the syndrome become apparent, they normally appear after the onset of puberty.[10]In humans, 47,XXY is the most common sex chromosome?aneuploidy?in males[11]?and the second most common condition caused by the presence of extra chromosomes. Other mammals also have the XXY syndrome, including mice.[12]Principal effects include? HYPERLINK "" \o "Hypogonadism" hypogonadism?and?sterility. A variety of other physical and behavioural differences and problems are common, though severity varies and many XXY boys have few detectable symptoms.Signs and symptoms[ HYPERLINK "" \o "Edit section: Signs and symptoms" edit]A person with typical untreated (surgery/hormones) Klinefelter 46,XY/47,XXY mosaic, diagnosed at age 19. Scar from?biopsy?may be visible on left?nipple.There are many variances within the XXY population, just as within the?46,XY?population. While it is possible to characterise XXY males with certain body types and physical characteristics, that in itself should not be the method of identification as to whether or not someone has XXY. The only reliable method of identification is?karyotype?testing. The degree to which XXY males are affected, both physically and developmentally, differs widely from person to person.PhysicalAs babies and children, XXY males may have weaker muscles and reduced strength. As they grow older, they tend to become taller than average. They may have less muscle control and coordination than other boys their age.[4]During puberty, the physical traits of the syndrome become more evident; because these boys do not produce as much testosterone as other boys, they have a less muscular body, less facial and body hair, and broader hips. As teens, XXY males may have larger breasts, weaker bones, and a lower energy level than other boys.[4]By adulthood, XXY males look similar to males without the condition, although they are often taller. In adults, possible characteristics vary widely and include little to no signs of affectedness, a?lanky, youthful build and facial appearance, or a rounded body type with some degree of? HYPERLINK "" \o "Gynecomastia" gynecomastia?(increased breast tissue).[13]?Gynecomastia is present to some extent in about a third of affected individuals, a slightly higher percentage than in the XY population. About 10% of XXY males have? HYPERLINK "" \o "Gynecomastia" gynecomastia?noticeable enough that they may choose to have cosmetic surgery.[3]Affected males are often?infertile, or may have reduced fertility. Advanced reproductive assistance is sometimes possible.[14]The term? HYPERLINK "" \o "Hypogonadism" hypogonadism?in XXY symptoms is often misinterpreted to mean "small testicles" or "small penis". In fact, it means decreased testicular hormone/endocrine function. Because of this (primary) hypogonadism, individuals will often have a low serum?testosterone?level but high serum?follicle-stimulating hormone?(FSH) and?luteinizing hormone?(LH) levels.[15]?Despite this misunderstanding of the term, however, it is true that XXY men may also have? HYPERLINK "" \o "Microorchidism" microorchidism?(i.e., small testicles).[15]XXY males are also more likely than other men to have certain health problems, which typically affect females, such as?autoimmune disorders,?breast cancer,?venous thromboembolic disease, and?osteoporosis.[4][16]?In contrast to these potentially increased risks, it is currently thought that rare?X-linked recessive?conditions occur less frequently in XXY males than in normal XY males, since these conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are typically only?carriers?rather than affected by these X-linked recessive conditions.Cognitive and developmentalSome degree of language learning or reading impairment may be present, HYPERLINK "" \l "cite_note-ped1988-18" [17]?and neuropsychological testing often reveals deficits in?executive functions, although these deficits can often be overcome through early intervention.[18]?There may also be delays in motor development which can be addressed through occupational therapy and physical therapy.[19]?XXY males may sit up, crawl, and walk later than other infants; they may also struggle in school, both academically and with sports.[4]CauseThe extra X chromosome is retained because of a?nondisjunction?event during?meiosis I?(gametogenesis). Nondisjunction occurs when homologous chromosomes, in this case the X and Y sex chromosomes, fail to separate, producing a sperm with an X and a Y chromosome. Fertilizing a normal (X) egg produces an XXY offspring. The XXY chromosome arrangement is one of the most common genetic variations from the XY?karyotype, occurring in about 1 in 500 live male births.[4]Another mechanism for retaining the extra X chromosome is through a nondisjunction event during?meiosis II?in the female. Nondisjunction will occur when sister chromatids on the sex chromosome, in this case an X and an X, fail to separate. (meiosis) An XX egg is produced which, when fertilized with a Y sperm, yields XXY offspring.In?mammals?with more than one X chromosome, the?genes?on all but one X chromosome are not expressed; this is known as?X inactivation. This happens in XXY males as well as normal XX females.[20]?However, in XXY males, a few genes located in the? HYPERLINK "" \o "Pseudoautosomal region" pseudoautosomal regions?of their X chromosomes, have corresponding genes on their Y chromosome and are capable of being expressed.[21]The first published report of a man with a 47,XXY karyotype was by Patricia Jacobs and?John Strong?at?Western General Hospital?in?Edinburgh, Scotland?in 1959.[22]?This karyotype was found in a 24-year-old man who had signs of Klinefelter syndrome. Jacobs described her discovery of this first reported human or mammalian chromosome?aneuploidy?in her 1981 William Allan Memorial Award address.[23]Variations48, HYPERLINK "" \o "XXYY" XXYY?and 48,XXXY occur in 1 in 18,000–50,000 male births. The incidence of 49,XXXXY is 1 in 85,000 to 100,000 male births.[24]?These variations are extremely rare. Additional chromosomal material can contribute to cardiac, neurological, orthopedic and other anomalies.Males with Klinefelter syndrome may have a?mosaic?47,XXY/46,XY constitutional?karyotype?and varying degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome is very rare. Thus far, only about 10 cases have been described in literature.[25]Analogous XXY syndromes are known to occur in?cats—specifically, the presence of?calico?or?tortoiseshell?markings in male cats is an indicator of the relevant abnormal karyotype. As such, male cats with calico or tortoiseshell markings are a?model organism?for Klinefelter syndrome.[26]DiagnosisAbout 10% of Klinefelter cases are found by?prenatal diagnosis.[28]?The first clinical features may appear in early?childhood?or, more frequently, during?puberty, such as lack of secondary sexual characters and? HYPERLINK "" \o "Aspermatogenesis" aspermatogenesis,[29]?while tall stature as a?symptom?can be hard to diagnose during puberty. Despite the presence of small testes, only a quarter of the affected males are recognized as having Klinefelter syndrome at puberty[30][31]?and 25% received their diagnosis in late adulthood: about 64% affected individuals are not recognized as such.[32]?Often the diagnosis is made accidentally as a result of examinations and medical visits for reasons not linked to the condition.[33]The standard diagnostic method is the analysis of the chromosomes'?karyotype?on?lymphocytes. In the past, the observation of the?Barr body?was common practice as well.[31]?To confirm? HYPERLINK "" \o "Mosaicism" mosaicism, it is also possible to analyze the karyotype using?dermal fibroblasts?or testicular tissue.[34]Other methods may be: research of high serum levels of?gonadotropins?(follicle-stimulating hormone?and?luteinizing hormone), presence ofazoospermia, determination of the sex?chromatin,[35]?and?prenatally?via?chorionic villus sampling?or?amniocentesis. A 2002 literature review of elective?abortion?rates found that approximately 58% of pregnancies in the United States with a diagnosis of Klinefelter syndrome were terminated.[36]Differential diagnosisThe symptoms of Klinefelter syndrome are often variable; therefore, a karyotype analysis should be ordered when small testes, infertility,? HYPERLINK "" \o "Gynecomastia" gynecomastia, long legs/arms, developmental delay, speech/language deficits, learning disabilities/academic issues and/or behavioral issues are present in an individual.[1]?The?differential diagnosis?for the Klinefelter syndrome can include the following conditions:?fragile X syndrome,? HYPERLINK "" \o "Kallmann syndrome" Kallmann syndrome?and? HYPERLINK "" \o "Marfan syndrome" Marfan syndrome. The cause of hypogonadism can be attributed to many other different medical conditions.There have been some reports of individuals with Klinefelter syndrome who also have other chromosome abnormalities, such as Down syndrome.[37]TreatmentThe genetic variation is irreversible. Often individuals that have noticeable breast tissue or? HYPERLINK "" \o "Hypogonadism" hypogonadism?experience depression and/or social anxiety because they are outside of social norms. This is academically referred to as?psychosocial?morbidity.[38]?At least one study indicates that planned and timed support should be provided for young men with Klinefelter syndrome to ameliorate current poor psychosocial outcomes.[38]By 2010 over 100 successful pregnancies have been reported using?IVF?technology with surgically removed sperm material from males with Klinefelter syndrome.[39]PrognosisChildren with XXY differ little from other children. Although they can face problems during?adolescence, often emotional and behavioural, and difficulties at school, most of them can achieve full independence from their families in adulthood. Most can lead a normal, healthy life.The results of a study carried out on 87?Australian?adults with the syndrome shows that those who have had a diagnosis and appropriate treatment from a very young age had a significant benefit with respect to those who had been diagnosed in adulthood.[40]There is research suggesting Klinefelter syndrome substantially decreases?life expectancy?among affected individuals, though the evidence is not definitive.[41]?A 1985 publication identified a greater?mortality?mainly due to diseases of the?aortic valve, development of? HYPERLINK "" \o "Tumor" tumors?and possible?subarachnoid hemorrhages, reducing life expectancy by about 5 years.[42]?Later studies have reduced this estimated reduction to an average of 2.1 years.[43]?These results are still questioned data, are not absolute, and will need further testing.[41]EpidemiologyThis syndrome, evenly spread in all?ethnic groups, has a?prevalence?of 1-2 subjects every 1000 males in the general population.[30][44][45][46]?3.1% of infertile males have Klinefelter syndrome. The syndrome is also the main cause of male? HYPERLINK "" \o "Hypogonadism" hypogonadism.[47]According to a meta-analysis, the prevalence of the syndrome has increased over the past decades; however, this does not appear to be correlated with the increase of the age of the mother at conception, as no increase was observed in the prevalence of other? HYPERLINK "" \o "Trisomies" trisomies?of sex chromosomes (XXX?and?XYY).[48]HistoryThe syndrome was named after?Harry Klinefelter, who, in 1942, worked with?Fuller Albright?at?Massachusetts General Hospital?in?Boston, Massachusetts?and first described it in the same year.[13][29]?The account given by Klinefelter came to be known as Klinefelter syndrome as his name appeared first on the published paper, and seminiferous tubule dysgenesis was no longer used.See alsoAneuploidyIntersexMosaic (genetics)True hermaphroditismTurner SyndromeXXYY syndromeNon-Klinefelter XXYTurner syndromeTurner syndrome?or?Ullrich–Turner syndrome?(also known as "Gonadal dysgenesis"[1]:550), 45,X, encompasses several conditions in humanfemales, of which? HYPERLINK "" \o "Monosomy" monosomy?X (absence of an entire sex chromosome, the?Barr body) is most common. It is a?chromosomal abnormality?in which all or part of one of the?sex chromosomes?is absent or has other abnormalities (unaffected humans have 46 chromosomes, of which two are sex chromosomes). In some cases, the chromosome is missing in some cells but not others, a condition referred to as? HYPERLINK "(genetics)" \o "Mosaic (genetics)" mosaicism[2]?or "Turner mosaicism".Occurring in 1 in 2000[3]?– 1 in 5000?phenotypic?females, HYPERLINK "" \l "cite_note-PedEndo-4" [4]?the syndrome manifests itself in a number of ways. There are characteristic physical abnormalities which affect many but not all people with Turner syndrome, such as?short stature,?swelling, broad chest, low hairline,?low-set ears, andwebbed necks.[5]?Girls with Turner syndrome typically experience gonadal dysfunction (non-working?ovaries), which results in?amenorrhea?(absence of menstrual cycle) and?sterility. Concurrent health concerns may also be present, including?congenital heart disease,?hypothyroidism?(reducedhormone?secretion by the?thyroid),?diabetes,?vision?problems,?hearing?concerns, and many autoimmune diseases.[6]?Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and?memory?areas.[7]Turner syndrome is named after?Henry Turner, the endocrinologist who first described it in 1938.Signs and symptomsLymphedema, puffy legs of a newborn with Turner syndromeThe following is a list of common symptoms of Turner syndrome. It is important to note that an individual may have any combination of symptoms and is unlikely to have all symptoms.Short statureLymphedema?(swelling) of the hands and feetBroad chest (shield chest) and widely spaced nipplesLow hairlineLow-set earsReproductive sterilityRudimentary ovaries gonadal streak (underdeveloped gonadal structures that later become fibrosed)Amenorrhoea, or the absence of a menstrual periodIncreased weight, obesityShield shaped thorax of heartShortened?metacarpal IVSmall fingernailsCharacteristic facial featuresWebbed neck?from?cystic hygroma?in infancyAortic valve stenosisCoarctation of the aortaBicuspid aortic valveHorseshoe kidneyVisual impairments?sclera,?cornea,?glaucoma, etc.Ear infections and hearing lossHigh waist-to-hip ratio (the hips are not much bigger than the waist)Attention Deficit/Hyperactivity Disorder or ADHD?(problems with concentration, memory, attention with hyperactivity seen mostly in childhood and adolescence)Nonverbal Learning Disability (problems with math, social skills and spatial relations)Other features may include a small lower jaw ( HYPERLINK "" \o "Micrognathism" micrognathia),? HYPERLINK "" \o "Cubitus valgus" cubitus valgus, HYPERLINK "" \l "cite_note-8" [8]?soft upturned nails, palmar crease, and?drooping eyelids. Less common are pigmented?moles, hearing loss, and a high-arch palate (narrow maxilla). Turner syndrome manifests itself differently in each female affected by the condition, therefore, no two individuals will share the same features.CauseTurner syndrome is caused by the absence of two complete copies of the X chromosome in some or all the cells. The abnormal cells may have only one X ( HYPERLINK "" \o "Monosomy" monosomy) (45,X) or they may be affected by one of several types of?partial monosomy?like a deletion of the short?p arm?of one X chromosome (46,XdelXp) or the presence of an? HYPERLINK "" \o "Isochromosome" isochromosome?with two q arms (46XiXq)[9]?In mosaic individuals, cells with X monosomy (45,X) may occur along with cells that are normal (46,XX), cells that have partial monosomies, or cells that have a Y chromosome (46,XY).[9]?The presence of mosaicism is estimated to be relatively common in affected individuals (67-90%).[9]InheritanceIn the majority of cases where monosomy occurs, the X chromosome comes from the mother.[10]?This may be due to a?nondisjunction?in the father.?Meiotic?errors that lead to the production of X with p arm deletions or abnormal Y chromosomes are also mostly found in the father.[11]? HYPERLINK "" \o "Isochromosome" Isochromosome?X or?ring chromosome?X on the other hand are formed equally often by both parents.[11]Overall, the functional X chromosome mostly comes from the mother.In most cases, Turner syndrome is a sporadic event, and for the parents of an individual with Turner syndrome the risk of recurrence is not increased for subsequent pregnancies. Rare exceptions may include the presence of a balanced?translocation?of the X chromosome in a parent, or where the mother has XO mosaicism restricted to her germ cells.[12]DiagnosisPrenatal45,X?karyotype, showing an unpaired X at the lower rightTurner syndrome may be diagnosed by?amniocentesis?or?chorionic villus sampling?during pregnancy.Usually, fetuses with Turner syndrome can be identified by abnormal?ultrasound?findings (i.e., heart defect, kidney abnormality,?cystic hygroma, HYPERLINK "" \o "Ascites" ascites). In a study of 19 European registries, 67.2% of prenatally diagnosed cases of Turner Syndrome were detected by abnormalities on ultrasound. 69.1% of cases had one anomaly present, and 30.9% had two or more anomalies.[13]An increased risk of Turner syndrome may also be indicated by abnormal triple or quadruple maternal serum screen. The fetuses diagnosed through positive maternal serum screening are more often found to have a mosaic karyotype than those diagnosed based on ultrasonographic abnormalities, and conversely those with mosaic karyotypes are less likely to have associated ultrasound abnormalities.[13]Although the recurrence risk is not increased,?genetic counseling?is often recommended for families who have had a pregnancy or child with Turner syndrome.PostnatalTurner syndrome can be diagnosed postnatally at any age. Often, it is diagnosed at birth due to heart problems, an unusually wide neck or swelling of the hands and feet. However, it is also common for it to go undiagnosed for several years, typically until the girl reaches the age of puberty/adolescence and she fails to develop properly (the changes associated with puberty do not occur). In childhood, a short stature can be indicative of Turner syndrome.[14]A test, called a?karyotype?or a chromosome analysis, analyzes the chromosomal composition of the individual. This is the test of choice to diagnose Turner syndrome.PrognosisWhile most of the physical findings are harmless, there can be significant medical problems associated with the syndrome.PrenatalDespite the excellent postnatal prognosis, 99% of Turner-syndrome conceptions are thought to end in spontaneous abortion or stillbirth,[15]?and as many as 15% of all spontaneous abortions have the XO karyotype.[16]?Among cases that are detected by routine amniocentesis or chorionic villus sampling, one study found that the prevalence of Turner syndrome among tested pregnancies was 5.58 and 13.3 times higher respectively than among live neonates in a similar population.[17]CardiovascularCardiovascular malformations are a serious concern as it is the most common cause of death in adults with Turner syndrome. They play an important part in the 3-fold increase in overall mortality and the reduced life expectancy (up to 13 years) associated with Turner syndrome. Price et al. (1986 study of 156 female patients with Turner syndrome) showed a significantly greater number of deaths from diseases of the circulatory system than expected, half of them due to?congenital heart defects?— mostly? HYPERLINK "" \o "Coarctation of the aorta" coarctation of the aorta. When patients with congenital heart disease were omitted from the sample of the study, the mortality from circulatory disorders was not significantly increased.[18]CauseAccording to Sybert, 1998 the data are inadequate to allow conclusions about?phenotype-karyotype?correlations in regard to cardiovascular malformations in Turner syndrome because the number of individuals studied within the less common karyotype groups is too small. Other studies also suggest the presence of hidden mosaicisms that are not diagnosed on usual karyotypic analyses in some patients with 45,X karyotype.In conclusion, the associations between karyotype and phenotypic characteristics, including cardiovascular malformations, remain questionable.Prevalence of cardiovascular malformationsThe prevalence of cardiovascular malformations among patients with Turner syndrome ranges from 17% (Landin-Wilhelmsen et al., 2001) to 45% (Dawson-Falk et al., 1992).The variations found in the different studies are mainly attributable to variations in non-invasive methods used for screening and the types of lesions that they can characterize (Ho et al., 2004). However Sybert, 1998 suggests that it could be simply attributable to the small number of subjects in most studies.Different karyotypes may have differing prevalence of cardiovascular malformations. Two studies found a prevalence of cardiovascular malformations of 30% HYPERLINK "" \l "cite_note-Mazzanti-19" [19]?and 38%[20]?in a group of pure 45,X monosomy. But considering other karyotype groups, they reported a prevalence of 24.3% HYPERLINK "" \l "cite_note-Mazzanti-19" [19]?and 11%[20]?in patients with mosaic X monosomy, and a prevalence of 11% in patients with X chromosomal structural abnormalities.[19]The higher prevalence in the group of pure 45,X monosomy is primarily due to a significant difference in the prevalence of?aortic valve?abnormalities and? HYPERLINK "" \o "Coarctation of the aorta" coarctation of the aorta, the two most common cardiovascular malformations.Congenital heart diseaseThe most commonly observed are congenital obstructive lesions of the left side of the heart, leading to reduced flow on this side of the heart. This includes?bicuspid aortic valve?and?coarctation(narrowing) of the aorta. Sybert, 1998 found that more than 50% of the cardiovascular malformations observed in her study of individuals with Turner syndrome were bicuspid aortic valves or coarctation of the aorta, alone or in combination.Other congenital cardiovascular malformations, such as partial anomalous venous drainage and?aortic valve stenosis?or aortic regurgitation, are also more common in Turner syndrome than in the general population.?Hypoplastic left heart syndrome?represents the most severe reduction in left-sided structuresBicuspid aortic valveUp to 15% of adults with Turner syndrome have bicuspid aortic valves, meaning that there are only two, instead of three, parts to the valves in the main?blood vessel?leading from the?heart. Since bicuspid valves are capable of regulating blood flow properly, this condition may go undetected without regular screening. However, bicuspid valves are more likely to deteriorate and later fail.Calcification?also occurs in the valves, HYPERLINK "" \l "cite_note-21" [21]?which may lead to a progressive valvular dysfunction as evidenced by aortic stenosis or regurgitation.[22]With a prevalence from 12.5% HYPERLINK "" \l "cite_note-Mazzanti-19" [19]?to 17.5% (Dawson-Falk et al., 1992), bicuspid aortic valve is the most common congenital malformation affecting the heart in this syndrome. It is usually isolated but it may be seen in combination with other anomalies, particularly coarctation of the aorta.Coarctation of the aortaBetween 5% and 10% of those born with Turner syndrome have coarctation of the aorta, a congenital narrowing of the descending aorta, usually just distal to the origin of the?left subclavian artery(the artery that branches off the arch of the aorta to the left arm) and opposite to the duct (and so termed "juxtaductal"). Estimates of the prevalence of this malformation in patients with Turner syndrome ranges from 6.9% HYPERLINK "" \l "cite_note-Mazzanti-19" [19]?to 12.5% . A coarctation of the aorta in a female is suggestive of Turner syndrome, and suggests the need for further tests, such as a karyotype.Partial anomalous venous drainageThis abnormality is a relatively rare congenital heart disease in the general population. The prevalence of this abnormality also is low (around 2.9%) in Turner syndrome. However, its relative risk is 320 in comparison with the general population. Strangely, Turner syndrome seems to be associated with unusual forms of partial anomalous venous drainage.[19][23]In the management of a patient with Turner syndrome it is essential to keep in mind that these left-sided cardiovascular malformations in Turner syndrome result in an increased susceptibility to bacterial endocarditis. Therefore prophylactic antibiotics should be considered when procedures with high risk endocarditis are performed, such as dental cleaning.[22]Turner syndrome is often associated with persistent?hypertension, sometimes in childhood. In the majority of Turner syndrome patients with hypertension, there is no specific cause. In the remainder, it is usually associated with cardiovascular or kidney abnormalities, including coarctation of the aorta.Aortic dilation, dissection, and ruptureTwo studies have suggested aortic dilatation in Turner syndrome, typically involving the root of the ascending aorta and occasionally extending through the aortic arch to the descending aorta, or at the site of previous coarctation of the aorta repair.[24]Allen et al., 1986 who evaluated 28 girls with Turner syndrome, found a significantly greater mean aortic root diameter in patients with Turner syndrome than in the control group (matched for body surface area). Nonetheless, the aortic root diameter found in Turner syndrome patients were still well within the limits.[25]This has been confirmed by the study of Dawson-Falk et al., 1992 who evaluated 40 patients with Turner syndrome.[26]?They presented basically the same findings: a greater mean aortic root diameter, which nevertheless remains within the normal range for body surface area.Sybert, 1998 points out that it remains unproven that aortic root diameters that are relatively large for body surface area but still well within normal limits imply a risk for progressive dilatation.[27]Prevalence of aortic abnormalitiesThe prevalence of aortic root dilatation ranges from 8.8% HYPERLINK "" \l "cite_note-Lin-24" [24]?to 42%[22]?in patients with Turner syndrome. Even if not every aortic root dilatation necessarily goes on to an?aortic dissection(circumferential or transverse tear of the intima), complications such as dissection, aortic rupture resulting in death may occur. The natural history of aortic root dilatation is still unknown, but it is a fact that it is linked to aortic dissection and rupture, which has a high mortality rate.[28]Aortic dissection affects 1% to 2% of patients with Turner syndrome. As a result any aortic root dilatation should be seriously taken into account as it could become a fatal aortic dissection. Routine surveillance is highly recommended.[22]Risk factors for aortic ruptureIt is well established that cardiovascular malformations (typically bicuspid aortic valve, coarctation of the aorta and some other left-sided cardiac malformations) and hypertension predispose to aortic dilatation and dissection in the general population. At the same time it has been shown that these risk factors are common in Turner syndrome. Indeed these same risk factors are found in more than 90% of patients with Turner syndrome who develop aortic dilatation. Only a small number of patients (around 10%) have no apparent predisposing risk factors. It is important to note that the risk of hypertension is increased 3-fold in patients with Turner syndrome. Because of its relation to aortic dissection blood pressure needs to be regularly monitored and hypertension should be treated aggressively with an aim to keep blood pressure below 140/80 mmHg. It has to be noted that as with the other cardiovascular malformations, complications of aortic dilatation is commonly associated with 45,X karyotype.[22]Pathogenesis of aortic dissection and ruptureThe exact role that all these risk factors play in the process leading to such fatal complications is still quite unclear. Aortic root dilatation is thought to be due to a mesenchymal defect as pathological evidence of cystic medial necrosis has been found by several studies. The association between a similar defect and aortic dilatation is well established in such conditions such asMarfan syndrome. Also, abnormalities in other?mesenchymal?tissues (bone matrix and lymphatic vessels) suggests a similar primary mesenchymal defect in patients with Turner syndrome.[24]However there is no evidence to suggest that patients with Turner syndrome have a significantly higher risk of aortic dilatation and dissection in absence of predisposing factors. So the risk of aortic dissection in Turner syndrome appears to be a consequence of structural cardiovascular malformations and hemodynamic risk factors rather than a reflection of an inherent abnormality in connective tissue (Sybert, 1998). The natural history of aortic root dilatation is unknown, but because of its lethal potential, this aortic abnormality needs to be carefully followed.PregnancyTurner syndrome is characterized by primary amenorrhea, premature ovarian failure, streak gonads and infertility. However, technology (especially oocyte donation) provides the opportunity of pregnancy in these patients.As more women with Turner syndrome complete pregnancy thanks to modern techniques to treat infertility, it has to be noted that pregnancy may be a risk of cardiovascular complications for the mother. Indeed several studies had suggested an increased risk for aortic dissection in pregnancy.[24]?Three deaths have even been reported. The influence of? HYPERLINK "" \o "Estrogen" estrogen?has been examined but remains unclear. It seems that the high risk of aortic dissection during pregnancy in women with Turner syndrome may be due to the increased hemodynamic load rather than the high estrogen rate.[22]?Of course these findings are important and need to be remembered while following a pregnant patient with Turner syndrome.Cardiovascular malformations in Turner syndrome are also very serious, not only because of their high prevalence in that particular population but mainly because of their high lethal potential and their great implication in the increased mortality found in patients with Turner syndrome. Congenital heart disease needs to be explored in every female newly diagnosed with Turner syndrome. As adults are concerned close surveillance of blood pressure is needed to avoid a high risk of fatal complications due to aortic dissection and rupture.SkeletalNormal skeletal development is inhibited due to a large variety of factors, mostly hormonal. The average height of a woman with Turner syndrome, in the absence of growth hormone treatment, is4 ft 7 in?(140?cm). Patients with Turner's mosaicism can reach normal average height.The fourth metacarpal bone (fourth toe and ring finger) may be unusually short, as may the fifth.Due to inadequate production of? HYPERLINK "" \o "Estrogen" estrogen, many of those with Turner syndrome develop?osteoporosis. This can decrease height further, as well as exacerbate the curvature of the spine, possibly leading to?scoliosis. It is also associated with an increased risk of?bone fractures.KidneyApproximately one-third of all women with Turner syndrome have one of three kidney abnormalities:A single, horseshoe-shaped kidney on one side of the body.An abnormal urine-collecting system.Poor blood flow to the kidneys.Some of these conditions can be corrected surgically. Even with these abnormalities, the kidneys of most women with Turner syndrome function normally. However, as noted above, kidney problems may be associated with?hypertension.ThyroidApproximately one-third of all women with Turner syndrome have a thyroid disorder.[ HYPERLINK "" \o "Wikipedia:Citation needed" citation needed]?Usually it is?hypothyroidism, specifically?Hashimoto's thyroiditis. If detected, it can be easily treated with thyroid hormone supplements.DiabetesWomen with Turner syndrome are at a moderately increased risk of developing?type 1 diabetes?in childhood and a substantially increased risk of developing?type 2 diabetes?by adult years. The risk of developing type 2 diabetes can be substantially reduced by maintaining a healthy weight.CognitiveTurner syndrome does not typically cause intellectual disability or impair cognition. However, learning difficulties are common among women with Turner syndrome, particularly a specific difficulty in perceiving spatial relationships, such as?nonverbal learning disorder. This may also manifest itself as a difficulty with motor control or with?mathematics. While it is non-correctable, in most cases it does not cause difficulty in daily living. Most Turner Syndrome patients are employed as adults and lead productive lives.There is also a rare variety of Turner Syndrome, known as "Ring-X Turner Syndrome", which has an approximate 60 percent association with intellectual disability. This variety accounts for approximately 2–4% of all Turner Syndrome cases.[29]ReproductiveWomen with Turner syndrome are almost universally?infertile. While some women with Turner syndrome have successfully become pregnant and carried their pregnancies to term, this is very rare and is generally limited to those women whose karyotypes are not 45,XO.[30][31]?Even when such pregnancies do occur, there is a higher than average risk of?miscarriage?or?birth defects, including Turner Syndrome or Down Syndrome.[32]?Some women with Turner syndrome who are unable to conceive without medical intervention may be able to use?IVF?or other fertility treatments.[33]Usually estrogen replacement therapy is used to spur growth of secondary sexual characteristics at the time when puberty should onset. While very few women with Turner Syndrome menstruate spontaneously, estrogen therapy requires a regular shedding of the uterine lining ("withdrawal bleeding") to prevent its overgrowth. Withdrawal bleeding can be induced monthly, like menstruation, or less often, usually every three months, if the patient desires. Estrogen therapy does not make a woman with nonfunctional ovaries fertile, but it plays an important role in assisted reproduction; the health of the uterus must be maintained with estrogen if an eligible woman with Turner Syndrome wishes to use IVF (using donated?oocytes).Turner syndrome is a cause of primary amenorrhea, premature ovarian failure (hypergonadotropic hypogonadism), streak gonads and infertility. Failure to develop secondary sex characteristics (sexual infantilism) is typical.Especially in mosaic cases of Turner syndrome that contains Y-chromosome (e.g. 45,X0/46,XY) due to the risk of development of ovarian malignancy (most common is gonadoblastoma) gonadectomy is recommended.[citation needed]TreatmentAs a chromosomal condition, there is no cure for Turner syndrome. However, much can be done to minimize the symptoms. For example: HYPERLINK "" \l "cite_note-tss_faq_6-34" [34]Growth hormone, either alone or with a low dose of?androgen, will increase growth and probably final adult height. Growth hormone is approved by the U.S.?Food and Drug Administration?for treatment of Turner syndrome and is covered by many insurance plans.[34][35]?There is evidence that this is effective, even in toddlers.[36]Estrogen replacement therapy?such as the birth control pill, has been used since the condition was described in 1938 to promote development of secondary sexual characteristics. Estrogens are crucial for maintaining good bone integrity, cardiovascular health and tissue health.[34]?Women with Turner Syndrome who do not have spontaneous puberty and who are not treated with estrogen are at high risk for osteoporosis and heart conditions.Modern?reproductive technologies?have also been used to help women with Turner syndrome become pregnant if they desire. For example, a donor egg can be used to create an embryo, which is carried by the Turner syndrome woman.[34]Uterine maturity is positively associated with years of estrogen use, history of spontaneous menarche, and negatively associated with the lack of current hormone replacement therapy.[37]EpidemiologyApproximately 99 percent of all fetuses with Turner syndrome result in spontaneous termination during the first trimester.[38]?Turner syndrome accounts for about 10 percent of the total number of spontaneous abortions in the United States.[citation needed]?The incidence of Turner syndrome in live female births is believed to be around 1 in 2000.[3]HistoryThe syndrome is named after?Henry Turner, an?endocrinologist?from Illinois, who described it in 1938.[39]?In Europe, it is often called?Ullrich–Turner syndrome?or even?Bonnevie–Ullrich–Turner syndrome?to acknowledge that earlier cases had also been described by European doctors.The first published report of a female with a 45,X?karyotype?was in 1959 by Dr. Charles Ford and colleagues in?Harwell, Oxfordshire?and?Guy's Hospital?in?London.[40]?It was found in a 14-year-old girl with signs of Turner syndrome.References: ................
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