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The further and higher educational experiences and consequent employability of women with the under-researched Triple X syndrome are arguably unknown. This research study examines their special edu...

Background: Fragile X syndrome (FXS) is a relatively common syndrome with numerous, multifaceted, and often unremarkable findings. Psychic alterations are at the forefront of treatment needs. Previous studies have provided evidence for an unusual sella turcica in some patients with FXS. This report adds to the up to now sparse findings on sella morphology in FXS. Case Report: The young patient with genetically confirmed FXS was treated for a mandibular tumor. Cone beam tomography of the skull revealed a prominent sella turcica with flat tuberculum sellae and steep clivus. Conclusion: Unusual sella turcica formations can be observed in FXS. A correlation with other discreet changes of FXS-related skeletal development is likely.

Individuals with sex chromosome trisomies (SCTs) have an increased risk of language delays and impairments. However, there are only a few data relative to their language development in early childhood. The present study aimed to investigate the preverbal skills shown by a group of 8-month-old children with SCTs to assess the presence of a possible early communicative delay. Moreover, the predictive role of early preverbal productions on later lexical development at 24 months was analysed. Twenty-six children with SCTs and 24 typically developing (TD) children participated in the study. Their use of vocal productions and gazes addressed to the communicative partner was assessed during a parent–child observation session held when the children were 8 months old. In addition, the children’s word comprehension at 8 months and their word production at 24 months were indirectly assessed by a parental report. Children’s word comprehension was similar in the two groups of children, whereas a significantly lower frequency per minute of gazes was found in children with SCTs than in TD children. A significantly lower proportion of children with SCTs showed the ability to produce babbling during the observation session, and significant differences were also found in the frequency of babbling utterances. No significant differences emerged among the subgroups of children with different types of SCTs. The predictive role of babbling on later lexical size was found in TD children but not in children with SCTs. This result could be probably explained by the small number of children in this group who could produce babbling utterances. The study leads to identify early signals of delay in the preverbal skills of children with SCTs. Early monitoring of their communicative development could help the clinicians in intervening with well-timed and targeted programmes.

The phenotype of triple X syndrome comprises a variety of physical, psychiatric, and cognitive features. Recent evidence suggests that patients are prone to severe language impairments. However, it remains unclear whether verbal impairments are pervasive at all levels of language, or whether one domain is relatively more spared than others. Here we document the language profile of one patient with triple X, using standardized language tests and reports. Results concur in showing that impairments are noticeable both in expressive and receptive language skills, and in vocabulary as well as in structural components of language. Although receptive ability in some tests appears relatively spared, even here A's performance is clearly below average. This single case study further underscores that language and communication at all levels can be severely compromised in patients with triple X. Practitioners should be aware of the limited language abilities that possibly exist in patients with triple X.

Background Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, and 13. However, reports on NIPT performance in sex chromosome aneuploidies (SCA) based on real clinical data are still limited. Methods High-throughput massively parallel genomic sequencing (MPS) technique was used to screen for fetal SCAs as part of the research to determine the potential value of NIPT in detecting fetal SCAs in the second trimester. A number of 12,243 consecutive cases from a single center were included in this study. Results The positive predictive value (PPV) of NIPT in the present study was 57.6%, which was divided and categorized by individual SCAs as follows: 21.4% for Turner syndrome (45,X), 75.0% for Triple X syndrome (47,XXX), 90.9% for Klinefelter syndrome (47,XXY), and 75.0% for XYY syndrome (47,XYY). Conclusion The NIPT-based SCA test cannot be used as a diagnostic method, and performing an invasive confirmation test on NIPT-based SCA-positive cases is strongly recommended.

PURPOSE: This study aimed to describe the comorbidity pattern in 47,XXX syndrome.METHODS: This was a registry-based study of hospital diagnoses and prescribed medication in a nationwide cohort of females with 47,XXX (n = 103) and 46,XX/47,XXX (n = 57) in which they were compared with 16,000 age-matched general population female controls.RESULTS: The overall occurrence of hospital diagnoses was significantly increased in females with 47,XXX when compared with controls (incidence rate ratio = 2.1, CI = 1.7-2.5), and when divided into 19 organ-specific groups, there was a significantly increased risk in the following 14 groups: infection, blood, endocrine and metabolism, mental, nervous system, eye, ear, respiratory, oral cavity and gastrointestinal, musculoskeletal, perinatal, congenital malformations, external factors, and "other." The risk of being prescribed any medication was not significantly increased in females with 47,XXX when compared with controls (hazard ratio = 1.2, CI = 0.9-1.4). However, when stratified according to medication groups, a significantly increased risk was detected in 4 of 13 groups. The overall occurrence of hospital diagnoses was also significantly increased when females with 46,XX/47,XXX were compared with controls (incidence risk ratio = 1.3, CI = 1.01-1.8), but generally, in comparison with controls, females with 46,XX/47,XXX were less severely affected than females with 47,XXX.CONCLUSION: The 47,XXX syndrome is associated with an increased occurrence of a wide variety of diseases. Increased awareness of this may contribute to improve counseling and clinical assessment of these patients.

BackgroundThe lack of understanding of molecular pathologies of the solitary functioning kidney makes improving and strengthening the continuity of care between pediatric and adult nephrological patients difficult. Copy number variations (CNVs) account for a molecular cause of solitary functioning kidney, but characterization of the pathogenic genes remains challenging.MethodsIn our prospective cohort study, 99 fetuses clinically diagnosed with a solitary functioning kidney were enrolled and evaluated using chromosomal microarray analysis (CMA). The genetic drivers for the pathogenic CNVs were analyzed. We characterized QPRT localization in fetal kidneys using immunohistochemistry and its expression in adult kidneys using quantitative RT-PCR. Further, QPRT was knocked down using siRNA in human embryonic kidney (HEK293T) cells, and the cell cycle and proliferation were tested.ResultsBesides one Triple X syndrome and one Down syndrome, we identified a total of 45 CNVs out of 34 subjects. Among the 14 pathogenic CNVs, CNV 16p11.2 reached the highest number of records with the phenotype of kidney anomalies in the Decipher database. Among the 26 genes within the 16p11.2 region, as a key enzyme for nicotinamide adenine dinucleotide (NAD+) biosynthesis, QPRT was distinctly localized in renal tubules but was barely observed in renal interstitial and glomeruli in fetal kidneys. The loss of QPRT prevented cells’ efficient transition into S phase, affected cell-cycle progression, and abrogated proliferation of human embryonic kidney cells.ConclusionOur data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney. The CNVs discovered in our study exhibit great potential for future applications in genetic counseling and pregnancy management.

Background Much interest has not been placed on the role of chromosomal abnormalities in the pathogenesis and rising prevalence of infertility in recent times. This review was conducted to renew public interest on the chromosomal basis of infertility, testing, and management. Main text Meiotic and post-zygotic mitotic errors may cause infertility-predisposing chromosomal abnormalities, including Klinefelter syndrome, Jacob syndrome, Triple X syndrome, Turner syndrome, and Down syndrome. Chromosomal abnormalities such as deletion, translocation, duplication, inversion, and ring chromosome may also predispose to infertility. Notable features of male chromosomal infertility include spermatogenic failure, characterized by azoospermia, oligospermia, and gonadal dysgenesis, while females include premature ovarian insufficiency, amenorrhea, spontaneous abortion, and gonadal dysgenesis. The risk of these abnormalities is influenced by maternal age and environmental factors such as chemical exposure, smoking, and alcohol consumption. Most chromosomal abnormalities occur spontaneously and are not treatable. However, early prenatal screening and diagnostic tests can lessen the effects of the conditions. There is also a growing belief that certain diets and drugs capable of changing gene expressions can be formulated to neutralize the effects of chromosomal abnormalities. Conclusion Meiotic and mitotic errors during gametogenesis and fetal development, respectively, can cause chromosomal abnormalities, which predispose to infertility. Couples who are at increased risk, particularly those with a family history of infertility and women at an advanced age (≥ 35 years), should seek medical advice before getting pregnant.

BackgroundTriple X syndrome (TXS) is caused by aneuploidy of the X chromosome and is associated with impaired social functioning in children; however, its effect on social functioning and emotion recognition in adults is poorly understood.AimsThe aim of this study was to investigate social functioning and emotion recognition in adults with TXS.MethodThis cross-sectional cohort study was designed to compare social functioning and emotion recognition between adults with TXS (n= 34) and an age-matched control group (n= 31). Social functioning was assessed with the Adult Behavior Checklist and Social Responsiveness Scale for Adults. Emotion recognition was assessed with the Emotion Recognition Task in the Cambridge Neuropsychological Test Automated Battery. Differences were analysed by Mann-WhitneyU-test.ResultsCompared with controls, women with TXS scored higher on the Adult Behavior Checklist, including the Withdrawn scale (P< 0.001, effect size 0.4) and Thought Problems scale (P< 0.001, effect size 0.4); and higher on the Social Responsiveness Scale for Adults, indicating impaired social functioning (P< 0.001, effect size 0.5). In addition, women with TXS performed worse on the Emotion Recognition Task, particularly with respect to recognising sadness (P< 0.005, effect size 0.4), fear (P< 0.01, effect size 0.4) and disgust (P< 0.02, effect size 0.3).ConclusionsOur findings indicate that adults with TXS have a higher prevalence of impaired social functioning and emotion recognition. These results highlight the relevance of sex chromosome aneuploidy as a potential model for studying disorders characterised by social impairments such as autism spectrum disorder, particularly among women.

Aim To investigate the epidemiology of chromosomal abnormalities (CA) in fetuses of all pregnancies based on a provincial-wide birth defects-monitoring system, which could provide scientific basis for making relatively policy and research. Methods Chromosomal abnormalities cases were collected from all hospitals in Hunan Province, China, between 2016 and 2019. The prevalence of CAs was calculated to examine associations among infant sex, maternal age and region. The rates of prenatal diagnosis and termination of pregnancy (TOP) involving CA or associated anomalies were calculated as rates or proportions. Results From 2016 to 2019, a total of 2 883 890 perinatal infants (28 weeks of gestation to postpartum 7 days) underwent prenatal screening and diagnostic tests, and 3181 fetuses were diagnosed as CA, with the prevalence of 11.03/10 000. The average prevalence of CAs was higher for male than female fetuses (11.33/10 000 vs 10.06/10 000) (OR = 1.13, 95% CI: 1.05-1.21), which was higher in urban areas than rural areas (23.03/10 000 vs 7.13/10 000) (OR = 3.23, 95% CI: 3.02-3.47), and the prevalence increased linearly with maternal age ( X trend 2 = 1821.844, P = 0.000). Among the fetuses with CAs, 3097 (97.36%) were diagnosed prenatally, and 3046 (98.35%) underwent TOP. The majority of CA were numerical abnormalities (90.18%). The main types of numerical autosomal abnormalities were trisomy 21 (6.69/10 000, 59.57%), trisomy 18 (1.13/10 000, 10.04%) and trisomy 13 (0.21/10 000, 1.88%). The main types of numerical gonosomal abnormalities were Klinefelter syndrome (0.68/10 000, 6.02%), Turner syndrome (0.49/10 000, 4.39%), Triple X syndrome (0.26/10 000, 2.29%) and 47,XYY syndrome (0.21/10 000, 1.91%). The three associated anomalies with the highest proportions were congenital heart defects (CHD) (41.06%), cleft palate or/and cleft lip (10.89%) and congenital talipes equinovarus (8.94%). Conclusion The prevalence of CA was lower than that reported. Chromosome detection should be further promoted including test contest and coverage, especially for urban areas, older mothers and fetuses with CHD, cleft palate or/and cleft lip or congenital talipes equinovarus.

Background Aneuploidy is one of the most important chromosomal aberrations, which involves an abnormal number of the chromosomes. Trisomy 21 (Down syndrome) and numerical aberrations of the sex chromosomes have a relatively high prevalence in the general population. However, the patients usually have one of the above genetic disorders and combined cases of two different trisomies are unusual. Case presentation We report a case of a patient with double aneuploidy—a combination of trisomy 21 and triple X syndrome. The proband had typical features of Down syndrome and did not manifest any symptoms of polysomy X. The patient had hypotonia, a cardiac defect, and an annular pancreas. A clinical diagnosis of Down syndrome was established, but the cytogenetic analysis found two free full trisomies—trisomy 21 (Down syndrome) and triple X. Conclusion Cases of double aneuploidy, combining trisomy 21 and trisomy of a sex chromosome, could be challenging because the patients manifest only symptoms, typical for Down syndrome. The discovery of a second complete free trisomy X in our case was an incidental finding. This illustrates the importance of the cytogenetic analysis, despite the evident phenotype of trisomy 21.

Identifying the factors related to adaptive functioning will improve the information available to families and providers of females with Trisomy X. Cognitive and behavioral features were assessed in 50 females ages 12.2 ± 3.6 years using the Behavior Assessment System for Children Second Edition (BASC-2) and Wechsler Scales of Intelligence. Executive functioning, social skills, and autistic traits were evaluated in a subset. Adaptive functioning was assessed using the BASC-2 adaptive skills composite score (ASC). Participants were classified as average adaptive skills (ASC T-score > 40) or deficits (ASC T-score

Triple-X syndrome is a common sex chromosome aneuploidy, which appears in 1 out of 1,000 females. The aim of our study was to describe the behavioral features of a large group of girls and women with triple-X in comparison to a control group. A total of 72 subjects with triple-X and 69 subjects of an age-matched control group were included. Psychological and behavioral questionnaires were allocated to three age groups, representing a range of ages from young childhood to adulthood. Regarding the females between 4 and 7 years of age, we found significant differences for social problems, attention problems, and school performance. For the age group 8-17 years, we found larger significant differences for the majority of the scales listed in the child behavior checklist. The most significant differences (p < .001) were from total behavior problems, internalizing problems, and four other scales. Young females with triple-X have significantly lower general self-esteem, especially concerning school and family. In the adults, there were significant differences concerning psychological symptoms and distress, with higher scores in the triple-X subjects. Regardless, their mean scores were still in the normal range. We did not find clinical evidence for more than 50% of the triple-X females in any age group, indicating that approximately half of them do not have behavioral problems, and that more than 60% do not differ in their competence from the control group. However, our findings suggest that triple-X influences mental health and the overall well-being of the individuals across their whole life spans.

We describe a case of a six-year-old girl who presents multiple dysmorphic features characteristic of Down’s syndrome. She has a significant general developmental delay, with a score that correspond to 32 months of developmental age. This delay is especially in language, with a very scant vocabulary. She communicates with some hand sign words or pointing, although her auditory responses in hearing test were normal. Two previous karyotype studies showed 47, XXX, +21 anomalies. This double trisomy is a rare condition described in isolated cases in the literature and none of these refers to the developmental aspects of these children (Balwan et al.2008; Li et al.2004; Park et al.1995; Day et al.1963). © 2018, Indian Academy of Sciences.

Ataxia-telangiectasia (AT) is a rare neurodegenerative disease characterized by an early onset ataxia, oculocutaneous telangiectasia, immunodeficiency, recurrent infections, radio-sensitivity, and a predisposition to malignancy. We present the case of a child with coexistent AT and trisomy X (47,XXX). We used fluorescent in situ hybridization (FISH) to confirm that this person had 47,XXX karyotype in blood cells, bone marrow, fibroblasts, and buccal smear. Standard cytogenetic studies (not banded) were conducted on blood cells. G-banding analysis was performed on bone marrow cells at the time of the leukemia diagnosis. Flow cytometric investigation of lymphocytes and Sanger sequencing of the ATM gene were used for diagnosis confirmation and description. We report the case of an 11-year-old girl at remission after having T cell acute leukemia for 7 years with progressive signs of ataxia-telangiectasia and with additional X chromosome since birth. At the age of 2 years and 7 months, she was diagnosed with pre-T acute leukemia. From the age of four, she had gait abnormalities. AT was established at the age of seven based on clinical signs and laboratory findings (increased alpha fetoprotein-AFP [227]) and confirmed by detecting compound heterozygous truncating mutations in the ATM gene (p.Y705X and p.L2312I). These genetic findings have not been previously reported in AT and our "double hit" case demonstrates the value of careful clinical evaluation of children with an established genetic diagnosis. Measurement of AFP levels should be considered in patients with neurologic abnormalities after leukemia 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. There is considerable variation in the phenotype, with some individuals very mildly affected and others with more significant physical and psychological features. However, the trisomy X in this case, without any of these phenotype, is rarely reported. Here, we report a case found during DNA sample collection in a study of genetic polymorphism analysis of loci in Chinese ethnic group, of a female with neither laboratory or clinical signs of Triple X syndrome. She was born at her mother's 60years old and her father's 62years old. Advanced maternal age was found acting as a significant risk factor of Triplo-X. Moreover, her child are also born without manifestations of 47, XXX syndrome. Pedigree study demonstrated the normal karyotype of the children. A diagnosis of 47XXX was made on the basis of a chromosomal study. Therefore, laboratory investigations (including PCR amplification, more than two kinds of X-STR genotyping, G-banding karyotyping analysis and Pedigree study) are applied to rule out the possibility of Mosaicism (45, X0/47, XXX) and ascertain her 47XXX karyotype without mosaic. The objective of this study was to report a case of trisomy X, diagnostic investigation and management of the case, and to analysis the genetically possible reasons behind the case. To our knowledge, this case is a rare one, found in DNA sample collection for the estimation of gene frequency in the process of genetic polymorphism study, of non-mosaic 47, XXX without signs of physical syndrome and born healthy children. In this study, it revealed that the proportion of trisomy X would be more than official statistics and risk of systemic disabilities is lower than estimated. Moreover, we found out that sample mixture and mosaicism act as the interference factors in forensic test. Therefore, we draw the conclusion that attentions and certain improved methods should be applied to the diagnosis of non-mosaic triple X, which is of great significance in decreasing the interruptions in the whole process of forensic and paternity identification.

Background Early diagnosis of Turner syndrome (TS) may improve preventive measures and treatment. X-chromosome inactivation specific differentially methylated CpG sites (XIDMSs) that are high methylated in inactive X chromosomes (Xi) and unmethylated in active X chromosomes (Xa) may be potential makers for TS detection. Methods The candidate XIDMSs were screened from 9 male and 12 female DNA samples with normal karyotypes using the Illumina 450k array and validated by bisulfite sequencing PCR and pyrosequencing assay. X chromosome dosage was calculated according to the methylation level of multiple XIDMSs. Results Overall, 108 candidate XIDMSs were screened by the 450k array. Validations indicated that XIDMSs gathered and formed the X-chromosome inactivation specific differentially methylated regions (XIDMRs). Using 3 XIDMRs at SAT1, UXT and UTP14A loci, 36 TS, 22 normal female and 6 male samples were analyzed. Methylation levels of the 20 XIDMSs in the XIDMRs could distinguish between TS and normal female DNA samples, the X chromosome dosage was consistent with karyotyping data. Analyzing samples of 2 triple X syndrome and 3 Klinefelter syndrome patients suggested that this method could be used to detect X chromosome aneuploids other than TS. Conclusions XIDMSs are widely spread along the X chromosome and might be effective markers for detection of TS and other X chromosome aneuploids.

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, chronic and systemic autoimmune disease generally with a more severe clinical phenotype than the adult-onset SLE. In both conditions, it is known that females are predominantly affected; therefore, the possible overlap of SLE and sex chromosomal abnormalities has attracted attention. Our case report describe the clinical manifestations and immunological profile of a Brazilian female with cSLE and trisomy X. The 22 year-old patient, diagnosed with cSLE at age of 11, present some features related to 47, XXX, such as difficulties at school and communication, although this was not enough to investigate for chromosome abnormalities. Cytoscan HD array screening allowed the comprehensive diagnosis for this patient. We also characterized her ancestral composition, showing that she has 6.2% higher African component than the mean from health subjects from the same geographical area. This report reinforces the role of the X chromosome dose effect for sex bias in SLE, as well as the importance of African ancestry composition in cLES. It also throws lights upon the application of high-throughput molecular analysis in a large scale cohort can be useful to detect the impact of the genomic findings for more accurate epidemiological data., Highlights • This report reinforces the role of the X chromosome dose effect for sex bias in SLE. • We highlight the importance of African ancestry composition in cSLE. • The application of high-throughput molecular analysis in a large scale cohort can be useful to detect the impact of the genomic findings for more accurate epidemiological data.

Triple X syndrome (trisomy X) is a sex chromosomal anomaly caused by the presence of an extra X chromosome. The patients with Triple X syndrome have a wide range of phenotypic variability. Some individuals are only mildly affected or asymptomatic. Epicanthal folds, clinodactyly, tall stature and hypotonia are the most commom phenotypic features. Patients also may have seizures, genitourinary abnormalities and premature ovarian failure. We report a patient with Triple X syndrome and cleft palate. By describing this case, we want to draw attention to the association between cleft palate and Triple X syndrome.

Background Certain constitutive chromosomal abnormalities of the human X chromosome are relatively common in conspicuous neuropsychiatric findings. Although tumors or tumor-like lesions are occasionally reported in diseases of the X chromosome, they are numerically negligible, for example, in aneuploidy such as the triple X syndrome (TXS). Case report A 16-year-old female patient with a known TXS and premutation stage of fragile X syndrome was referred by her dentist for diagnosis and treatment of unilateral cheek swelling. The examination of the psychologically conspicuous patient revealed a unilateral mandibular tumor with dysesthesia of the mental nerve. Surgical removal of soft, crumbly spongiosa over the nerve canal resulted in sufficient pressure release of the constricted nerve and restoration of epicritic sensitivity. Imaging findings and histological and molecular genetic examination revealed monostotic craniofacial fibrous dysplasia. Conclusion Although the data in the literature do not give reason to suppose an accumulation of neoplasms in TXS, a numb chin syndrome should be a reason for detailed diagnostics. Careful diagnosis allows for customized therapy. This is the first report on the coincidence of TXS, fragile X syndrome, and fibrous dysplasia in a single individual.

Amac: Triple X sendromu (47, XXX), kadinlarda ekstra bir X kromozomunun varligi ile karakterize, 1/1.000 kiside bir gorulen bir sendromdur. Trizomi X, degisken siddette bilissel ve davranissal ozelliklerle karakterize bir kromozomal hastaliktir. Bu olgu sunumunda; Triple X sendromlu ve direncli sizofreni tanisi alan 16 yasinda bir vaka sunuyoruz. Genetik sendromlarin psikiyatrik problemlerin tedavisinde tedaviye direncle iliskili olabilecegi ve bu nedenle tedaviye direncli olgularda genetik analizlerin mutlaka yapilmasi gerektigi goz onunde bulundurulmalidir.

AIMS Recent studies have revealed that the interplay between polygenic risk scores (PRS) and large copy number variants (CNV; >500kb) is essential for the etiology of schizophrenia (SCZ). To replicate previous findings, including those for smaller CNV (>10kb), the PRS between SCZ patients with and without CNV were compared. METHODS The PRS were calculated for 724 patients with SCZ and 1178 healthy controls (HC), genotyped using array-based comparative genomic hybridization and single nucleotide polymorphisms chips, and comparisons were made between cases and HC, or between subjects with and without 'clinically significant' CNV. RESULTS First, we replicated the higher PRS in patients with SCZ compared to that in HC (without taking into account the CNV). For clinically significant CNV, as defined by the American College of Medical Genetics ('pathogenic' and 'uncertain clinical significance, likely pathogenic' CNV), 66 patients with SCZ carried clinically significant CNV, whereas 658 SCZ patients had no such CNV. In the comparison of PRS between cases with/without the CNV, despite no significant difference in PRS, significant enrichment of the well-established risk CNV (22q11.2 deletion and 47,XXY/47,XXX) was observed in the lowest decile of PRS in SCZ patients with the CNV. CONCLUSION Although the present study failed to replicate the significant difference in PRS between SCZ patients with and without clinically significant CNV, SCZ patients with well-established risk CNV tended to have a lower PRS. Therefore, we speculate that the CNV in SCZ patients with lower PRS may contain 'genuine' risk; PRS is a possible tool for prioritizing clinically significant CNV because the power of the CNV association analysis is limited due to their rarity.

Persistent migraine aura without infarction is a rare but debilitating condition. Treatment options are mostly anecdotal and limited due to inefficacy and side effects. We present a 16-year-old female patient with triple X syndrome, having persistent aura symptoms for over 2 years, consisting of continuous visual and sensory sensations. Previous treatments with seven different migraine preventatives were not successful. The patient successfully responded to zonisamide against refractory prolonged aura and remained symptom-free under the ongoing treatment without any relevant side effects. Zonisamide may be considered a new and safe treatment option for patients with persistent migraine aura.

In human subjects, the sex chromosomes are the X and the Y chromosomes. Normally, a complement of two X chromosomes (46,XX) is seen in females and one X and one Y (46,XY) in males. The X-chromosome includes about 1500 genes, only a few of which are involved in sex development. The Y-chromosome contains very few genes, but one gene, SRY, is the most important gene in male sex development. Multiple autosomal genes are also involved in sex development. Abnormalities of sex chromosomes can involve errors in the number of sex chromosomes, such as 45,X0 (Turner syndrome), 47,XXX, 47,XXY (Klinefelter syndrome), 47,XYY or mosaicism. Sex chromosome abnormalities also include aberrations of a single gene of the sex chromosome, leading to a disorder of sex development (DSD). This can result in 46,XX DSD and 46,XY DSD. Key Concepts Turner syndrome occurs when females have a missing sex chromosome (45,X0) or have a mosaic complement of cells with one or more lines missing a sex chromosome. Girls with Turner syndrome have a variety of congenital anomalies, the most striking being short stature and premature ovarian failure. Klinefelter syndrome boys (47,XXY) have tall stature, marfinoid habitus, and may have difficulty with language development and verbal IQ (intelligent quotient). 46,XY complete gonadal dysgenesis, or Swyer syndrome, describes patients who have both external and internal female organs with a 46,XY chromosome complement. 46,XY disorders of sex development encompass a wide range of disorders including androgen insensitivity, partial gonadal dysgenesis and many more. 46,XX disorders of sex development can result from a multitude of virilising disorders or the presence of Y-chromosome material. Patients with disorders of sex development and intra-abdominal gonads may be at risk for gonadoblastoma, depending on their underlying disorder. Assignment of sex, timing of surgery and medical management of patients with disorders of sex development is controversial. Keywords: Turner syndrome; Klinefelter syndrome; triple X syndrome; the 47,XYY syndrome; 46,XX DSD; 46,XY DSD; gonadal dysgenesis; androgen insensitivity; Swyer syndrome

Objectives: Cell-free fetal DNA has been widely used in prenatal genetic testing during recent years. We explored the feasibility of non-invasive prenatal testing (NIPT) for analysis of common fetal aneuploidies among pregnancies in northwest China. Material and methods: A total of 8594 maternal blood samples were collected from October 2014 to December 2017 in the Department of Obstetrics and Gynecology at the First Affiliated Hospital of the Air Force Medical University. Cases with positive screening results by NIPT detection were validated using karyotype analysis. Results: Of 8594 clinical pregnancies, 88 had positive NIPT results and 78 of 88 (88.6%) positive NIPT results were shown to be false-positive by amniotic fluid puncture and chromosome karyotyping analysis. There were 44 cases (49.44%) with trisomy 21, 18, and 13 syndromes (30 cases of trisomy 21, 9 cases of trisomy 18, and 5 cases of trisomy 13). There were 44 cases (50.56%) with sex chromosome abnormalities, including 11 cases with Turner syndrome (45, X), 17 cases with Triple X syndrome (47, XXX), 2 cases with Klinefelter syndrome (47, XXY), and 14 cases with 47, XYY syndrome (47, XYY). Conclusions: The accuracy, specificity, high efficiency, and acceptance of NIPT can effectively avoid birth defects and improve the quality of the birth population. We should deepen mining and analysis of the clinical data and explore ways to use NIPT. It is recommended that the NIPT guidelines be extended to low-risk patients to further explore the impact of a significant increase in screening.

Background: Knowledge on the prevalence of sex chromosome abnormalities (SCAs) is limited, and delayed diagnosis or non-diagnosis of SCAs are a continuous concern. We aimed to investigate change over time in incidence, prevalence and age at diagnosis among Turner syndrome (TS), Klinefelter syndrome (KS), Triple X syndrome (Triple X) and Double Y syndrome (Double Y). Methods: This study is a nationwide cohort study in a public health care system. The Danish Cytogenetic Central Registry (DCCR) holds information on all karyotypes performed in Denmark since 1961. We identified all individuals in the DCCR with a relevant SCA during 1961-2014; TS: n = 1156; KS: n = 1235; Triple X: n = 197; and Double Y: n = 287. From Statistics Denmark, which holds an extensive collection of data on the Danish population, complete data concerning dates of death and migrations in and out of Denmark were retrieved for all individuals. Results: The prevalence among newborns was as follows: TS: 59 per 100,000 females; KS: 57 per 100,000 males; Triple X: 11 per 100,000 females; and Double Y: 18 per 100,000 males. Compared with the expected number among newborns, all TS, 38% of KS, 13% of Triple X, and 18% of Double Y did eventually receive a diagnosis. The incidence of TS with other karyotypes than 45,X (P < 0.0001), KS (P = 0.02), and Double Y (P = 0.03) increased during the study period whereas the incidence of 45,X TS decreased (P = 0.0006). The incidence of Triple X was stable (P = 0.22). Conclusions: The prevalence of TS is higher than previously identified, and the karyotypic composition of the TS population is changing. Non-diagnosis is extensive among KS, Triple X and Double Y, whereas all TS seem to become diagnosed. The diagnostic activity has increased among TS with other karyotypes than 45,X as well as among KS and Double Y.

Background Orofacial clefts are the most common malformations of the head and neck region. Genetic and environmental factors have been implicated in the etiology of these traits. Methods We recently conducted genotyping of individuals from the African population using the multiethnic genotyping array (MEGA) to identify common genetic variation associated with nonsyndromic orofacial clefts. The data cleaning of this dataset allowed for screening of annotated sex versus genetic sex, confirmation of identify by descent and identification of large chromosomal anomalies. Results We identified the first reported orofacial cleft case associated with paternal uniparental disomy (patUPD) on chromosome 22. We also identified a de novo deletion on chromosome 18. In addition to chromosomal anomalies, we identified cases with molecular karyotypes suggesting Klinefelter syndrome, Turner syndrome and Triple X syndrome. Conclusion Observations from our study support the need for genetic testing when clinically indicated in order to exclude chromosomal anomalies associated with clefting. The identification of these chromosomal anomalies and sex aneuploidies is important in genetic counseling for families that are at risk. Clinicians should share any identified genetic findings and place them in context for the families during routine clinical visits and evaluations.

We report our findings in a 3-year-old girl who was suspected of having triple X syndrome because she was taller than +4.35 standard deviations for her age. She also had high myopia. Optical coherence tomography (OCT) showed that her retinas were thin, the lenses were subluxated, and the axial length was elongated. Our findings indicate that for a female child with tall stature, there should be thorough evaluations for endocrinological disorders, overgrowth syndromes, connective tissue disorders, and genetic disorders. If there are also behavioral issues, this may lead to consideration of 47 XXX in a female or 47 XXY in a male infant. The 47 XXX syndrome is a potential and neglected cause for tall stature and requires a high index of suspicion.

Purpose The purpose of this paper is to establish the value of clinical genetic diagnostics in the lives of people with an intellectual disability (ID), their families, and their primary and professional caregivers. It has been shown that psychologists are more likely to make use of the opportunities offered by clinical genetic diagnostics if they have seen the psychological benefits in their own practice. Moreover, this paper aims to promote the practice of informing people with ID, their families, and other caregivers regarding the current technological advances in genetic diagnostics, thereby allowing these patients to decide for themselves whether to utilise these opportunities. Design/methodology/approach The authors report four case studies in which the psychosocial value to each patient is pivotal. Findings In these four cases, it is clear the medical model can augment the social model by providing an interpretation of its meaningfulness in the lives of the people concerned. Research limitations/implications Case studies alone can have limited scientific significance. This approach examining the significance of clinical genetic diagnosis should be studied further in larger groups. Practical implications It is hoped that psychologists and other professional caregivers will become enthused about the value of clinical genetic diagnostics and will choose to discuss the option of referral for clinical genetic diagnostics with their patients more often. Social implications People with an ID who are seeking mental health care, and their caregivers, should be given the opportunity to take part in the decision regarding whether to use clinical genetic diagnostics, which may even have a destigmatising effect. Originality/value Quality of life may improve for people with an ID seeking mental healthcare and for their caregivers as well by opening up discussion regarding the opportunities presented by clinical genetic diagnostics. The fact that people are able to make their own choices based on their own considerations can have a destigmatising effect.

Women with X chromosome aneuploidy such as 45,X (Turner syndrome) or 47,XXX (Triple X syndrome) present with characteristics including differences in stature, increased cardiovascular disease risk and primary ovarian insufficiency. Many women with X chromosome aneuploidy undergo lifetime clinical monitoring for possible complications. However, ascertainment of cases in the clinic may mean that the phenotypic penetrance is overestimated. Studies of prenatally ascertained X chromosome aneuploidy cases have limited follow-up data and so the long-term consequences into adulthood are often not reported. We aimed to characterise the prevalence and phenotypic consequences of X chromosome aneuploidy in a large population of women over 40 years of age. We detected 30 women with 45,X, 186 with mosaic 45,X/46,XX and 110 with 47,XXX among 244,848 UK Biobank women, using SNP array data. The prevalence of non-mosaic 45,X (1/8,162) and 47,XXX (1/2,226) was lower than expected, but was higher for mosaic 45,X/46,XX (1/1,316). The characteristics of women with 45,X were consistent with the characteristics of a clinically recognised Turner syndrome phenotype, including a 17.2cm shorter stature (SD = 5.72cm; P = 1.5 × 10−53) and 16/30 did not report an age at menarche. The phenotype of women with 47,XXX included taller stature (5.3cm; SD = 5.52cm; P = 5.8 × 10−20), earlier menopause age (5.12 years; SD = 5.1 years; P = 1.2 x 10−14) and a lower fluid intelligence score (24%; SD = 29.7%; P = 3.7 × 10−8). In contrast, the characteristics of women with mosaic 45,X/46,XX were much less pronounced than expected. Women with mosaic 45,X/46,XX were less short, had a normal reproductive lifespan and birth rate, and no reported cardiovascular complications. In conclusion, the availability of data from 244,848 women allowed us to assess the phenotypic penetrance of traits associated with X chromosome aneuploidy in an adult population setting. Our results suggest that the clinical management of women with 45,X/46,XX mosaicism should be minimal, particularly those identified incidentally.FundingNone

Background Bladder exstrophy is a rare malformation. Prenatal diagnosis is usually an incidental finding on routine ultrasound examination. Triple-X syndrome (karyotype 47,XXX) is the most frequent sex chromosome aneuploidy in live-born females (approximately 1 in 1000). The diagnosis is often not made because women with 47,XXX karyotype have no or hardly any clinical symptoms during life. Methods Prenatal diagnosis of triple X karyotype is usually an incidental finding when an invasive prenatal diagnosis is performed for other reasons. Results Here, we report on two cases with bladder exstrophy and triple-X syndrome, one in a fetus and one in an adult. In view of two previous reports of this association in literature, causality of these two conditions should be considered. Conclusion A gene dosage effect as possible underlying mechanisms will be discussed. Birth Defects Research (Part A) 100:797–800, 2014. © 2014 Wiley Periodicals, Inc.

A 46-year-old female presented to the emergency room due to the chief complaint of left-sided weakness. By imaging study, she was diagnosed with cerebral infarction. Thrombolytic and antiplatelet agents were not considered due to the "golden hour" for treatment having passed and a low platelet count. The peripheral blood smear, bone marrow biopsy, and aspirate findings were consistent with immune thrombocytopenic purpura. The chromosome analysis revealed the 47,XXX karyotype. To the best of our knowledge, this is the first case report associated with the comorbidities of cerebral infarction, idiopathic thrombocytopenic purpura, and triple X syndrome.Kırk altı yaşındaki kadın hasta başlıca şikayeti sol tarafındaki zayıflık olarak acil servise başvurdu. Görüntüleme çalışmaları sonucu serebral enfarktüs tanısı kondu. Tedavi için değerli “altın saatler”in geçmiş olması ve düşük trombosit değerleri sebebiyle trombolitik tedavi ve antiagregan tedavi başlanmadı. Hastanın çevre kanı yayması, kemik iliği biyopsisi ve aspirasyonu immün trombositopenik purpura ile uyumluydu. Kromozom incelemesinde 47,XXX karyotip tayin edildi. Bilgilerimize göre, bu olgu serebral enfarkt, idyopatik trombositopenik purpura komorbiditelerinin birlikte bulunduğu ilk triple X sendromudur.

Lipid metabolism abnormalities in children may be hereditary or secondary to certain diseases (obesity, type 2 diabetes mellitus). Often elevated triglycerides values are associated with high cholesterol values, playing a major role on atherosclerosis. The triple X syndrome also called “the superfemale syndrome” is not a rare condition, but it is usually undiagnosed or occasionally diagnosed when other investigations are done. The authors present the case of a child admitted in the 3rd Clinic of Pediatrics -“Sf. Maria” Children’s Emergency Hospital, Iaşi -Romania for the continuation of her lipid metabolism investigations, being diagnosed on this occasion with the triple X syndrome. We conclude that the investigation of lipid metabolism, early identification of lipid abnormalities and proper treatment significantly reduce the prevalence of cardiovascular disease in adults. We cannot specify the impact of the presence of the chromosomal anomaly, as it is an accidental association

Triple X syndrome is a sex chromosome abnormality characterised by extra X chromosome, occurring in 1 in 1000 female births. This condition often remains undiagnosed as most of them have normal phenotype, puberty and fertility. We report a case of Triple X syndrome with normal phenotype and intelligence presented with premature ovarian failure, recurrent abortion and secondary infertility. This case emphasizes the need for chromosomal analysis in women presenting with premature ovarian failure leading to recurrent abortion and secondary infertility.

Background: Turner syndrome (TS) is a gonadal dysgenesis related to partial or total lack of one of the X chromosomes. It this report we describe a young patient presenting some somatic features of TS, who underwent spontaneous puberty and was eumenoorheic up to the age of 23.Methods: Using fluorescent in situ hybridization (FISH) mosaic karyotype (45X[131]/47XXX[9]) of TS and triple X syndrome was found.Results: She presented uncommon for TS somatic hemihypotrophy and underwent growth hormone and surgical therapy. The patient was diagnosed with premature ovarian failure when she was 23, with absent follicular reserve. Clinical features of this case and a few published cases will be reviewed briefly.

This report describes a patient with autoimmune myelofibrosis accompanied by Sjögren's syndrome (SS). A 36-year-old woman was admitted due to petechiae, purpura, gingival bleeding, dyspnea on exertion, and a lack of concentration. She had pancytopenia and was diagnosed with SS. A bone marrow study showed hypercellular marrow with reticulin fibrosis. Lymphocytic infiltrates and aggregates composed of a mixture of T and B cells in the marrow were also observed. A chromosomal analysis of the marrow cells showed 47, XXX and an analysis of peripheral lymphocytes revealed 47, XXX/46, XX mosaic results. The patient's cytopenia resolved following treatment with oral prednisolone.

Triple X syndrome (47,XXX) is a numerical chromosomal alteration that affects 1/1,000 women, in which the woman is born with an extra X chromosome. Some oral changes have been reported in the literature, as hypodontia, influence on deposition of crown enamel and discrepancies in cephalometric measurements. Other systemic complications may lead to oral abnormalities similar to those seen in triple X patients, such as congenital hypothyroidism (CH). This paper reports a triple X syndrome case associated with CH later treated. Besides delay in cognitive and intellectual development, the patient had changes in teeth development and in cephalometric measurements with deficiencies in the maxilla and mandible. This is the first report of a triple X syndrome associated with CH. Both conditions may result in changes in dentofacial development.

Fetal congenital chylothorax is a rare condition that occurs sporadically or can be associated with abnormal karyotype or structural chromosomal anomalies. We report a unique case of fetal congenital bilateral chylothorax associated with mosaicism 47,XXX/46,XX. A female fetus affected by massive bilateral hydrothorax and ascites was diagnosed at 34(+1) weeks of gestation. Previous ultrasonographic exams were completely normal. Immune causes of hydrops were excluded. Elective cesarean section was performed soon after bilateral thoracocentesis. The analysis of drained pleural fluid revealed its lymphatic nature. The fetal karyotyping, performed on chorionic villi at the 11th week, had shown mosaicism 47,XXX/46,XX, later confirmed in the newborn's blood. We hypothesized that chylothorax may be part of the phenotypic spectrum of 47 XXX karyotype and we suggest an ultrasound follow-up of the fetus at closer intervals than the routine timing for this condition, even if it is not usually characterized by severe phenotypic features.

Aim The effect of a supernumerary X chromosome on bones has not been reported and this study evaluated bone mineral status and metabolism in non-mosaic triple X syndrome. Methods This cross-sectional study comprised 19 girls, with a median age of 10.9 years, with nonmosaic triple X syndrome and a control group matched for age and body size. We studied ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels and urinary deoxypyridinoline concentrations. We also measured the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) Z-scores. Results Patients with non-mosaic triple X showed significantly reduced AD-SoS (p

Aim: The objective of this study was to correlate the genotype, of female patients, withshort stature and primary amenorrhea. Materials and Methods: One hundred and forty-six subjects were recruited during 2005-2012. Microscopic and automated karyotyping analyses were done by using chromosomes isolated from the lymphocytes using Giemsa banding (GTG) to identify chromosome abnormalities. Results: A total of 146 clinically suspected Turner syndrome (TS) subjects were recruited for the study, of which, 61 patients were identified to have chromosome abnormalities. The chromosomal abnormalities detected were as follows: Monosomy X (n = 19, 13.01%), triple X syndrome (n = 4, 2.7%), mosaic TS (n = 12, 8.21%), XY gonadal dysgenesis (n = 13, 8.9%), and structural abnormalities including X chromosome (n = 15, 10.27%) and one patient each with autosomal changes involving 9qh inversion and translocation of chromosomes 12 and 14. Conclusion: Karyotype abnormalities accounting for 46% in this study emphasize the need for karyotype testing in cases of short stature with primary amenorrhea.

Factors are reviewed that contribute to the contemporary view of a disproportionate prevalence and incidence of SLE in females. Recent studies on the epidemiology of SLE report that global incidences and prevalences of SLE for Caucasian and Black populations are of the order of 5.5 and 13.1 per year and 81 and 212 per 100,000 persons respectively. Both parameters displayed age dependent variation over a 90-year lifespan. The female to male (F:M) incidence of SLE varied with age, being approximately 1 during the first decade of life, followed by a sharp increase to 9 during the 4th decade, thence declining in subsequent decades before an increase during the 7th or 8th decade. A cognate review of SLE diagnosis in neonates revealed a F:M ratio of ≈1.2, consistent with the epidemiology review and the sporadic nature of SLE. Notional estimates of disease duration showed a steady increase from a base level for both males and females. The linear trend line for males was always lower than the trend line for females, supporting clinical experience that SLE is a more severe disease in males. Over a 14-year interval ending in 2012, the notional duration of SLE increased from 10-15years to 20-25years, probably reflecting advances in diagnosis and clinical practice. A metastudy of SLE concordance in twins revealed a 75% discordance in monozygotic twins compared to a 95% discordance in dizygotic twins confirming the importance of environmental factors in susceptibility to SLE. The elevated discordance in dizygotic SLE twins (and between siblings) suggests a role for the intrinsic genomic sexual dimorphism due to divergence of Y chromosome regulatory loci from their X chromosome homologues due to lack of recombination of mammalian sex chromosomes over evolutionary time. Estimates were made of the incidences of SLE in males and females based on population data for nine autosomal deficiency loci of major effect, plus expected male prevalence associated with Klinefelter's syndrome and female prevalence associated with Triple X syndrome. These genetic abnormalities accounted for ≈4% of female and ≈23% of male Caucasoid prevalence and for SLE resulting in a F:M ratio of ≈0.17. It may be deduced therefore that the impressive preponderance of SLE in females arises from a combination of environmental triggers and susceptibility loci of relatively small effect acting between the interval from the mini-puberty of childhood to the peak of reproductive adulthood. It is in this cohort of females, and especially in the Black population, that combinations of loci of minor effect acting together with environmental factors initiate defective apoptosis resulting in consequential autoimmune disease especially SLE. We postulate that because apoptosis is itself a very complex process, and defective apoptosis is an important contributor to SLE, there will be many combinations of susceptibility loci and environmental stimuli that can result in SLE (and other autoimmune disease(s)), of varying severity.

Sex chromosome aneuploidies (SCA) is a group of conditions in which individuals have an abnormal number of sex chromosomes. SCA, such as Klinefelter’s syndrome, XYY syndrome, and Triple X syndrome are associated with a large range of neurological outcome. Another genetic event such as another cytogenetic abnormality may explain a part of this variable expressivity. In this study, we have recruited fourteen patients with intellectual disability or developmental delay carrying SCA associated with a copy-number variant (CNV). In our cohort (four patients 47,XXY, four patients 47,XXX, and six patients 47,XYY), seven patients were carrying a pathogenic CNV, two a likely pathogenic CNV and five a variant of uncertain significance. Our analysis suggests that CNV might be considered as an additional independent genetic factor for intellectual disability and developmental delay for patients with SCA and neurodevelopmental disorder.