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Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females 47,XXX instead of 46,XX. Seizures, renal and genitourinary abnormalities, and premature ovarian failure POF can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined.

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The pseudoautosomal regions of the human sex chromosomes Free xxx nude child A Rappold. Nat Genet. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. San Diego: College Hill Press; Gastrointestinal problems, including constipation and abdominal pain, are also common concerns [ 222 ]. Cytogenet Cell Genet. Italian Danish Don't take your children!! Pediatr Res.

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A House Energy and Commerce subcommittee held a hearing on combating online sex trafficking and reviewing the legislation…. By using this site, you agree Free xxx nude child the Terms of Use and Privacy Policy. The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. In Wikipedia Add links. Misinformation is a real threat. Free Speech Coalition, U. Moeders met kinderen zonnebaden op auto-vrij Amstelveld, Bestanddeelnr Feee In latespecial agents recovered a database of hundreds of additional individuals whose credit cards had been Free xxx nude child while subscribing to the "Illegal. Penis lills tuscaloosa Wikipedia Add links. CP" website between November and February

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Very Interesting,A lot of stuff going on,like bands half naked people,Funny people,Crazy people,Again not a place for young children. We went here on a Saturday night and it was full of people.

Lots of them. There are stores lining both sides of the street along with casinos and places to eat. An overhead zip line and street vendors as well as some odd street performers.

The Fremont Street is closed to cars. Plenty of neon lights so you feel safe as long as you don't get off the main drag. The slots seemed to pay better than on the strip. We even went back Sunday for a few hours and had a good time.

We had a 3 day pass for the bus and that was our transportation up and down the strip while there. I've been going to Vegas for about 30 years now and have never made it to Fremont Street, so go if you get an opportunity.

I'll be back there. Every time we come to Vegas we go to Fremont Street. Its like a big block party with everyone having a good time. Plenty of food and alcohol. But the best part is the people watching. So many performers and very unique people to watch. Good music and light shows. Definitely not a place for snobby people, but people that like to hang out and have a good time.

THIS is a must see. NO rain and no wind. Sooo much fun!!! If it's your first time in Vegas, you must visit Fremont at least once, At night around pm hang out at The D. Flights Vacation Rentals Restaurants Things to do.

Las Vegas. Profile JOIN. Log in to get trip updates and message other travelers. Don't take your children!! A lot of XXX Fremont Street Experience. A lot of XXX rated people standing around. Review of Fremont Street Experience. Date of experience: February Thank Terry H. See all 42, reviews.

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Time of year. Language All languages. All languages. English 35, Spanish 2, Portuguese 1, French 1, German Italian Japanese Dutch Chinese Sim. Chinese Trad. Russian Korean Danish Swedish Hebrew Norwegian Polish Hungarian 9. Turkish 9. Arabic 6. Indonesian 5. Finnish 3. Thai 3. Greek 1. Serbian 1. Slovak 1. Show reviews that mention. All reviews light show zip line old vegas golden nugget people watching free concerts street entertainers older casinos the main strip every hour container park old school downtown vegas the deuce lots of fun mob museum bands.

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Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females 47,XXX instead of 46,XX. Seizures, renal and genitourinary abnormalities, and premature ovarian failure POF can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years.

The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined.

Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated for POF. Patients should be referred to support organizations to receive individual and family support. The prognosis is variable, depending on the severity of the manifestations and on the quality and timing of treatment.

Trisomy X 47,XXX is a sex chromosome aneuploidy condition in which females have an extra X chromosome, compared to the 46,XX karyotype in typical females.

It was first described in in a year-old woman with normal intellectual abilities who presented with secondary amenorrhea at 19 years of age [ 1 ]. Since the initial description, only several hundred cases have been described, identifying a variety of associated developmental, psychological, and medical features.

These studies were conducted in the 's and 80's at multiple centers across the U. This manuscript reviews the current literature available describing features associated with trisomy X, with recognition that much of the literature is based on small sample sizes and clinical ascertainment of patients, and does not likely represent the full spectrum of females with trisomy X.

However, review of the current knowledge is necessary to provide a summary of background and treatment recommendations for patients and professionals, and to highlight the many areas of need for additional research in trisomy X.

Significant facial dysmorphology or striking physical features are not commonly associated with 47,XXX, however, minor physical findings can be present in some individuals including epicanthal folds, hypertelorism, upslanting palpebral fissures, clinodactyly, overlapping digits, pes planus, and pectus excavatum. Hypotonia and joint hyperextensibility may also be present [ 2 , 7 ].

Variable facial features in girls with trisomy X. A few cases have been ascertained due to tall stature [ 8 ], and current evaluation of tall stature in females should include karyotype analysis to evaluate for 47,XXX. Cases of short stature have also been described unrelated to a known 45,X mosaicism , and one prospective study identified a subgroup of 47,XXX girls with heights below the 50 th percentile [ 9 ]. Body segment proportions typically show long legs, with a short sitting height [ 10 ].

Studies of bone age have shown no significant differences from 46,XX females [ 11 ]. The average head circumference is below the 50 th percentile, however, there is a lot of individual variation. Congenital heart defects have also been described including cases of atrial and ventricular septal defects, pulmonic stenosis, and aortic coarctation [ 15 - 17 ]. Seizure subtypes including absence, partial, and generalized seizures have been described, with good responses to standard anticonvulsant treatments [ 18 - 21 ].

Gastrointestinal problems, including constipation and abdominal pain, are also common concerns [ 2 , 22 ]. Pubertal onset and sexual development are usually normal in trisomy X, however, there have been cases of ovarian or uterine dysgenesis described in children and young adults with trisomy X.

Premature ovarian failure POF is a condition in which the ovarian functions of hormone production and oocyte egg development become impaired before the typical age for menopause. There are multiple case reports of women with trisomy X found to have POF, with endocrine findings of hypergonadotropic hypogonadism. The ages of these cases have ranged from 19 to 40 years [ 1 , 23 , 24 ]. Studies on the prevalence of POF in adolescents or adults with trisomy X have not yet been performed.

Precocious puberty has also been described but is not a typical finding. There is significant variability in the developmental and psychological features of children and adults with trisomy X, ranging from those with minimal involvement to those with clinically significant problems requiring comprehensive intervention services.

Thus, individual evaluation of developmental and psychological problems known to be associated with trisomy X is important in each individual. Infants and toddlers are at increased risk for early developmental delays, especially in speech-language development and motor development related to hypotonia. Average age at walking independently is Prospective studies comparing girls with trisomy X at 24 months of age to sibling controls show impairments in speech and language development.

However, other patients show impairments in both expressive and receptive language [ 28 ]. Speech and language deficits may continue throughout childhood into adulthood, with higher level language difficulties including problems with language processing, verbal fluency, language comprehension, and pragmatic language in some patients [ 2 , 28 , 29 ].

Studies on cognitive abilities in trisomy X also show a wide range of cognitive skills, with full scale IQ's ranging from across various studies [ 28 - 34 ]. Adapted and reprinted with permission from Bender et. Motor skill deficits may also be present. Walking may be delayed, and decreased muscle tone and lack of coordination are often clinically significant.

An extensive motor study of 10 children with trisomy X showed ongoing motor planning difficulties and overall weaknesses in motor skills and motor coordination, along with gait abnormalities and poor joint stability [ 2 , 38 ].

Attentional problems, poor executive function, and decreased adaptive functioning skills may also impact educational and home functioning. Childhood anxiety and language weaknesses are a difficult combination for affected children as the demanding verbal environments often found in school settings can exacerbate anxiety and result in behavioral difficulties.

Language deficits may also impact social adjustment in some children when they have difficulty communicating with playmates and when self-expression is limited in older children and adolescents. Social immaturity relative to peers may be present, and this, along with cognitive and executive function impairments, can make some girls with trisomy X vulnerable to social pressures from peers and victimization.

Other mental health disorders including adjustment disorders, mood disorders and psychotic disorders have been described in case series and reports [ 2 , 41 - 43 ], and comprehensive studies evaluating features of these disorders in the trisomy X population are needed. A comprehensive review of trisomy X literature with an emphasis on mental health has recently been published by Otter et al. Again, the variability in the phenotype needs to be emphasized, since many females with trisomy X have minimal cognitive, social, or emotional difficulties.

Since the longitudinal studies of the 's and 80's of females with trisomy X followed into adulthood, there have been very few additional research studies focused exclusively on this genetic disorder. A neuroimaging study conducted in in 10 girls with trisomy X from the original longitudinal cohort in Denver mean age Another MRI study of 12 girls with trisomy X mean age The significance or neuropathological findings of these white matter abnormalities are not yet known, however, they suggest that gene dosage effects from sex chromosome genes affect white matter development.

In typical 46,XX females, only one X chromosome in each cell is genetically active and the other is inactivated through DNA methylation and the accumulation of a histone variant throughout the chromosome [ 49 ]. X-inactivation occurs early in blastogenesis and is controlled by the X chromosome inactivation center XIC , which counts the X chromosomes present and randomly inactivates all but one X chromosome per diploid set.

However, particular segments of the X chromosome, known as the pseudoautosomal regions PAR1 and PAR2 , have Y chromosome homologs and therefore are not inactivated and remain genetically active [ 50 , 51 ].

Thus, in trisomy X, two of the three X chromosomes are inactivated, however, genes in the PAR regions and other genes that escape X-inactivation are expressed from the three X chromosomes. It is hypothesized that the phenotypic abnormalities associated with trisomy X result from overexpression of these genes on the X chromosome that escape X-inactivation [ 30 , 52 , 53 ].

While there is some microarray evidence of overexpression of X-chromosome genes in cells lines with supernumerary X chromosomes [ 54 ], the specific genes involved in the phenotype of trisomy X and other sex chromosome aneuploidies have not been identified. One exception is the SHOX gene, which escapes X-inactivation and is associated with the short stature seen in Turner syndrome and the tall stature in supernumerary sex chromosome aneuploidy conditions [ 55 , 56 ].

Trisomy X occurs from a nondisjunction event, in which the X chromosomes fail to properly separate during cell division either during gametogenesis resulting in a trisomic conceptus , or after conception known as post-zygotic nondisjunction. Similar to other trisomies, trisomy X has been shown to have a statistically significant correlation with advancing maternal age, as the likelihood of nondisjunction events during meiosis increases with increasing maternal age.

It is also important to identify mosaicism with a Turner syndrome 45,X cell line in order to determine appropriate medical evaluations and treatments needed for Turner syndrome.

The physical and psychological manifestations of trisomy X are variable, and a karyotype should be considered in females presenting with:. Developmental and behavioral features in trisomy X can be similar to those seen in females with fragile X syndrome.

Females suspected of having fragile X with a negative fragile X test should have a karyotype completed to evaluate for trisomy X [ 16 ].

Females with pentasomy X typically have short stature [ 56 ]. Due to features in the newborn period such as hypotonia, hypertelorism and epicanthal folds, some patients with trisomy X are ascertained by karyotype performed due to suspicion for trisomy 21 or trisomy 21 mosaicism. Other genetic conditions associated with tall stature could also be considered depending on the clinical presentation, such as Marfan syndrome long limbs, hyperextensibility , and the Sotos' and Beckwith-Weidemann syndromes cognitive impairments.

Adolescents or adult females presenting with POF should be tested for trisomy X, Turner syndrome, and the fragile X premutation, and should have further evaluation to identify other possible medical causes of POF.

Individuals with these diagnoses should be further evaluated medically to determine if testing for trisomy X or other medical conditions is indicated. In these cases, additional genetic and medical evaluation is warranted to rule out other disorders, since these may co-exist with trisomy X due to the high incidence of births.

Karyotype testing of females presenting with short stature and a Turner syndrome phenotype have shown findings of nonmosaic 47,XXX in blood lymphocytes, however, genetic testing of another tissue such as skin biopsy or buccal cells identified 45,X mosaicism [ 59 ].

Thus, individuals found to have trisomy X with a Turner syndrome phenotype should have a second tissue type analyzed by cytogenetic or FISH studies to further evaluate for a 45,X cell line since this changes treatment recommendations. Genetic counseling for prenatally diagnosed cases of trisomy X should address the medical, developmental, and psychological manifestations of the condition as outlined in this review.

As noted, there is significant variability in developmental delays, learning disabilities and psychological characteristics in trisomy X and it is not yet possible to predetermine which child will exhibit any or all of these concerns.

Couples with a recent diagnosis may be eager to search the internet for information about trisomy X and they should be cautioned about the excessive inaccurate and biased information they may find. Couples should be informed that the occurrence of trisomy X is due to a random event, that there is nothing that they did to cause or prevent the occurrence.

It is important for parents to appreciate the significant role of other genes inherited, stressing that the child's prognosis is relative to their entire genetic makeup, as well as the impact of environmental factors.

In addition, a study of females with trisomy X by Robinson et al. However, this study may be biased as it was based on a small sample of patients and did not control for several environmental influences, such as socioeconomic status and family support.

These rates are lower compared to other sex chromosome aneuploidy conditions due to the lack of association with infertility and other serious medical problems, and the broad phenotypic variability.

When discussing the diagnosis with the child, it is important to use terminology that is straightforward and developmentally appropriate. Young children should be given simple, age-appropriate information on a fairly regular basis allowing them to grow, cope and adjust to the information over time. Discussions with adolescents and young adult children should be straightforward with full disclosure.

Use of the term "sex" or "sex chromosome" should be used with caution, as children and adolescents can confuse the diagnosis with their sexuality or misconstrue the diagnosis as having a "sex abnormality. Genetic counseling for adult patients should additionally address potential reproductive issues, specifically POF and the risk of transmission.

While fertility in women with trisomy X is generally considered normal, there is an increased risk for POF as noted within this review, which may be important to consider in family planning. It is important that this risk be presented independently of the risks due to maternal age. These transmission risks apply only to women with non-mosaic 47,XXX, as mosaicism may increase the risk of X aneuploidy and potential outcomes, so each scenario should be considered individually [ 3 , 72 , 73 ].

Evaluation and treatment recommendations depend on the age of the patient and severity of the phenotype, however, all individuals should undergo a medical history and physical examination with an emphasis on features requiring monitoring and intervention as outlined in this review. Infants and children with trisomy X should undergo evaluation for the psychological and medical features of the disorder.

In infants and young children, a renal ultrasound and cardiac evaluation should be obtained. Constipation should be treated as needed. Medical history should include questions regarding staring spells or atypical movements, since seizure disorders and electroencephalogram EEG abnormalities can be present in females with trisomy X and may present as partial or absence seizures.

In these cases, EEG studies should be performed to rule out possible seizure activity.

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