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Introduction: The dual diagnosis of Down syndrome and Turner syndrome in the same patient was clinically identified in the early 1950s before the development of karyotyping techniques. After that, several authors reported anecdotal patients and/or reviewed series of Down-Turner double aneuploidies due to a regular 46,X,+21 constitution or different combinations of abnormal cell lines. In such cases, the most typical presentation encompasses the female sex, Down syndrome phenotype, and chromosomal mosaicism. Case Presentation: Here we report a female patient presenting with short stature, dysmorphic features, developmental delay, and learning disabilities, whose karyotype revealed a previously undescribed 45,X[47]/48,XXX,+21[3] constitution. Conclusion: This is the first case encompassing these three aneuploidies together and, contrary to most previous reports, exhibiting a predominantly Turner syndrome phenotype associated with developmental delay. [ABSTRACT FROM AUTHOR]

Introduction: Trisomy X is a sex chromosome (47,XXX) abnormality with a variable phenotype characterized by tall stature and premature ovarian failure with primary or secondary amenorrhea. Early postnatal diagnosis of trisomy X is difficult because most of the newborn girls have a normal phenotype. In childhood, girls often show muscle hypotonia, developmental delay, speech, cognitive and behavioral difficulties. The most common physical signs include epicanthial folds, hypertelorism, and clinodactyly. Some girls have a variety of seizures, cardiac and renal abnormalities. Patients: We present two girls with Triple X syndrome. The first girl was diagnosed at the age of 16.7 years, with secondary amenorrhea (three years after menarche), tall stature (90р) and rougher facial features. The hormonal profile showed hypergonadotropic hypogonadism, and undetectable level of AMH. Patient 2 was a 17 years old girl with tall stature (>97р) and normal menstrual cycle 4 years after menarche. The hormonal profile showed normal levels of gonadotropins and estradiol, but low level of AMH, indicating diminished ovarian reserve. Both girls had karyotype 47,XXX, without speech problems, communication or learning difficulties, or autoimmune conditions. Conclusion: The presented patients show the need for a comprehensive approach in girls with tall stature with or without menstrual disorders, including performing of a timely cytogenetic diagnostics. Earlier diagnosis, multidisciplinary care and the available reproductive technologies are an opportunity to preserve their fertility and quality of life. [ABSTRACT FROM AUTHOR]

The present study reports a patient case with a 17α-hydroxylase deficiency accompanied by triple X syndrome. A 17α-hydroxylase deficiency leads to a very low 17α-hydroxylated steroid synthesis as well as a non-feedback increase in the adrenocorticotropic hormone level. Meanwhile, the progesterone level increases the 17α-hydroxyprogesterone level and decreases the dehydroepiandrosterone sulfate level. The patient is characterized by intractable hypokalemia, high urinary potassium, hyperaldosteronemia, hyporeninemia, hypocortisolemia, hypertension, gonadal and secondary sexual dysplasia, a decreased estrogen level, primary amenorrhea, and infertility. The imaging findings indicate a presence of multiple bilateral adrenal gland adenomas, and the sequencing indicates a missense CYP17A1-E7 gene pathogenic variant. The karyotype is a 47, XXX [3]/46, XX [47] low-level chimeric karyotype. The patient’s parents are cousins. To our knowledge, this patient is the first case diagnosed with congenital adrenal hyperplasia caused by hydroxylase deficiency and triple X syndrome. The uniqueness of this case is that this patient has two very rare genetic diseases, probably due to the marriage of close relatives.

The etio-pathophysiology of obsessive-compulsive disorder (OCD) can be explained using a biopsychosocial model. Little is known about obsessive-compulsive symptoms (OCS) in the context of chromosomal disorders involving the X chromosome. Case studies of two patients with chromosomal disorders involving the X chromosome (Patient 1 with a variant of Turner syndrome and Patient 2 with triple X syndrome). Both patients were treated due to severe OCS. In the research MRI analysis, the most pronounced MRI change in both patients was a gray matter volume loss in the orbitofrontal cortex. Patient 1 additionally showed left mesiotemporal changes. Patient 2 presented with global gray matter volume reduction, slowing in EEG, and a reduced intelligence quotient. OCS could occur in the context of Turner syndrome or triple X syndrome. The detected MRI changes would be compatible with dysfunction of the cortico-striato-thalamo-cortical loops involved in OCD pathophysiology. Further studies with larger patient groups should investigate whether this association can be validated. [ABSTRACT FROM AUTHOR]

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

Women with Triple X syndrome (TXS) appear to be at increased risk for decreased ovarian reserve; however, available data are limited. We present an asyndromic adult female with features of recurrent pregnancy loss and decreased ovarian reserve detected with mosaic Triple X syndrome (TXS). The patient was initially evaluated by a low-cost peripheral blood (PB) conventional karyotyping using standard cytogenetic protocols. Interphase fluorescence in situ hybridisation was performed to confirm the diagnosis. Chromosomal microarray, which is a more expensive test, substantiated the presence of additional X chromosomes but failed to detect the presence of low level of mosaicism. Our case study emphasised the recommendation of performing a strategy-based cost-effective cytogenetic evaluation of all cases of decreased ovarian reserve or low anti-Müllerian hormone levels in a resource-constrained setting. It also highlighted the need for additional research to understand the natural history of ovarian function in TXS affected women throughout their lifespans. [ABSTRACT FROM AUTHOR]

Background. Women with triple X syndrome (TXS) have an extra X chromosome. TXS appeared to be associated with psychiatric disorders in biased or underpowered studies. Aim. This study aims to describe the prevalence of psychiatric disorders in adults with TXS in a relatively large and less biased group of participants. Method. In this cross-sectional study, data were collected from 34 women with TXS (mean age = 32.9; s.d. = 13.1) and 31 controls (mean age = 34.9; s.d. = 13.7). Psychiatric disorders were assessed using the MINI International Neuropsychiatric Interview (MINI) and the adult behavior checklist (ABCL). Trait and state anxiety were assessed using the State–Trait Anxiety Inventory. Results. In the TXS group, MINI results showed a higher prevalence of major depressive episodes (43.3%), psychotic disorders (29.4%), and suicidality (23.5%). Only 50% of the TXS group earned a normal score for the total syndrome score using the ABCL. In addition, levels of trait anxiety were higher in the TXS group. Only three women in each group received psychotropic medication. Impaired social functioning appeared to represent a major risk factor in TXS as regards psychotic, affective disorders, trait anxiety, and low self-esteem. Conclusions. Women with TXS are vulnerable to developing psychiatric disorders, and women with both TXS and impaired social functioning are even more vulnerable. [ABSTRACT FROM AUTHOR]

Triple X syndrome is the most common sex chromosome aneuploidies (SCA) in females. Still, it is underdiagnosed because patients are usually without clear dysmorphism, and the syndrome is not associated with any significant congenital anomalies. We are reporting a case of a 5-year-old girl who presented with aplastic anemia, confirmed by a bone marrow aspiration and biopsy. Her complete workup showed that she has three copies of chromosome X, which, given the diagnosis of triple X syndrome, requires a supportive treatment but not a bone marrow transplant. Few cases of aplastic anemia with sex chromosome abnormalities have been reported. We are reviewing the triple X syndrome in different aspects of the presentation. [ABSTRACT FROM AUTHOR]

Purpose: Triple X syndrome, is an often undiagnosed chromosomal abnormality with an incidence of 1/1000 females. Main associated disorders are urogenital malformations, premature ovarian failure or primary amenorrhea, gastrointestinal problems, psychiatric disorders and epilepsy. To date, triple X is not related to a specific epileptic syndrome. Therefore, the purpose of this clinical series is to analyze seizure semiology, electroencephalogram features and the long-term outcome of 13 patients with epilepsy and triple X syndrome.Methods: We retrospectively evaluated the long-term seizure outcome in patients with triple X syndrome who had been referred to 11 Epilepsy Centers in Italy. A close electroclinical follow-up was made for at least 2 years and outcomes were reported.Results: Our case series confirms that epilepsy is not an occasional finding but part of the phenotypic spectrum of this syndrome. The seizure semiology shows an higher prevalence of focal seizures in 62% of patients. EEG findings of focal epileptic activity were reported in 85% of patients. Anti-seizure medications were successful in all our patients whom in most cases were responsive to monotherapy.Conclusion: According to our case series most successful drugs were VPA and LEV. Long term prognosis of epilepsy in our case series was good. Our experience suggests that all triple X patients achieve good seizure control and in 69% of cases normalization of the EEG. [ABSTRACT FROM AUTHOR]

Objective: 47,XXX is a form of sex chromosome anomaly with an extra copy of X chromosome. It can have a varying presentation ranging from a few physical characteristics to intellectual and learning disabilities to primary ovarian insufficiency (POI). Although for most triple X syndrome patients, sexual development and fertility are normal, a few may present with amenorrhea and POI. We are presenting a case of triple X patient who presented with POI at 23 years of age. The relatively rare occurrence of this entity prompted us to report this case. Case Presentation: Index case was presented to us at 23 years of age with secondary amenorrhea and desire for conception. Secondary sex characteristics were normal except for axillary hair that was scanty. Workup revealed a 47, XXX karyotype and a diagnosis of POI was made. We are presenting this case to highlight this important entity as a differential in cases of amenorrhea and to discuss the fertility options available in such cases. Conclusion: Women with triple X syndrome have varying phenotypic presentations. Those presenting with POI will need hormone replacement therapy, psychological support and counselling for fertility options.

Abstract Background Women with triple X syndrome (TXS) have an extra X chromosome. TXS appeared to be associated with psychiatric disorders in biased or underpowered studies. Aim This study aims to describe the prevalence of psychiatric disorders in adults with TXS in a relatively large and less biased group of participants. Method In this cross-sectional study, data were collected from 34 women with TXS (mean age = 32.9; s.d. = 13.1) and 31 controls (mean age = 34.9; s.d. = 13.7). Psychiatric disorders were assessed using the MINI International Neuropsychiatric Interview (MINI) and the adult behavior checklist (ABCL). Trait and state anxiety were assessed using the State–Trait Anxiety Inventory. Results In the TXS group, MINI results showed a higher prevalence of major depressive episodes (43.3%), psychotic disorders (29.4%), and suicidality (23.5%). Only 50% of the TXS group earned a normal score for the total syndrome score using the ABCL. In addition, levels of trait anxiety were higher in the TXS group. Only three women in each group received psychotropic medication. Impaired social functioning appeared to represent a major risk factor in TXS as regards psychotic, affective disorders, trait anxiety, and low self-esteem. Conclusions Women with TXS are vulnerable to developing psychiatric disorders, and women with both TXS and impaired social functioning are even more vulnerable.

Clinical manifestations of triple X syndrome (karyotype 47, XXX) can include autoimmune diseases. We describe the occurrence of acquired thrombotic thrombocytopenic purpura (TTP), an autoimmune condition, refractory to plasmapheresis and rituximab in a patient with triple X syndrome who required vincristine administration for disease remission. To our knowledge, this rare coexistence is the first of its kind reported in Brazil., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Clinical Hospital Complex of the Federal University of Paraná, Curitiba, Paraná, Brazil. issued approval 6.920.024. In view of the above, the Human Research Ethics Committee of the HC-UFPR, in accordance with the attributions defined in CNS Resolution 466/2012 and in CNS Operational Standard No. 001/2013, expresses its approval of the Case Report , as proposed. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, da Rocha Ribas et al.)

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Triple X syndrome is the most common sex chromosome aneuploidies (SCA) in females. Still, it is underdiagnosed because patients are usually without clear dysmorphism, and the syndrome is not associated with any significant congenital anomalies. We are reporting a case of a 5-year-old girl who presented with aplastic anemia, confirmed by a bone marrow aspiration and biopsy. Her complete workup showed that she has three copies of chromosome X, which, given the diagnosis of triple X syndrome, requires a supportive treatment but not a bone marrow transplant. Few cases of aplastic anemia with sex chromosome abnormalities have been reported. We are reviewing the triple X syndrome in different aspects of the presentation.

This report aims to investigate the association between 47,XXX and fetal hydrops by examining a clinical case and performing a comprehensive review of the relevant literature. A 34-year-old Japanese woman, gravida 2, para 1, was diagnosed with fetal hydrops at 27 weeks' gestation. Prenatal testing revealed a 47,XXX karyotype. Interventions included thoracocentesis and a thoracoamniotic shunt. A cesarean delivery was performed at 34 weeks and the female neonate initially had respiratory challenges. After 69 days in the neonatal intensive care unit, the infant was discharged in stable condition, and the 47,XXX karyotype was confirmed. This case may add evidence suggesting an association between 47,XXX and fetal hydrops. Chromosomal abnormalities are causes of fetal hydrops, but its association with 47,XXX remains unclear. Providing comprehensive information on this condition to couples is crucial, and considering the inclusion of fetal hydrops in the list of associated conditions might be advisable., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sugai et al.)

Abstract 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

Background Triple 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. Aims The aim of this study was to investigate social functioning and emotion recognition in adults with TXS. Method This 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-Whitney U-test. Results Compared 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). Conclusions Our 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 educational needs (where relevant), and their negotiation of conventional educative systems, throughout the stages of post-compulsory education and into the world of work. The prevalent individualist societal focus means that education bodies promote their qualification offers for students to gain individual employability currency, in order to secure their own futures. Ten women with Triple X were asked to reflect on their post-compulsory education experiences, considering their varying developmental and cultural barriers to access, and their employability skill set against the background of the likelihood of their transferring this to a position of graduate employment. Findings illustrate the significance of socio-economic background and support network, as well as varying individual cognitive capacity and also health status in participants being able to varying degrees, to secure a sense of stability and contentment: yet no woman secured graduate employment. By way of a further conclusion this research discloses the systemic lack of awareness of the existence of Triple X on the part of educational bodies and employers, a problem which further research is needed to address. [ABSTRACT FROM AUTHOR]

Despite affecting in 1 in every 1000 females, remarkably little is known about trisomy X syndrome (47,XXX), especially among older adults who are undiagnosed. In this study, we aimed to determine the prevalence of 47,XXX among females enrolled in the Million Veterans Program (MVP; mean age 50.2 ± 13.6 years), and compare broad health outcomes between females with 47,XXX and 46,XX matched controls. We identified 61 females with an additional X chromosome, corresponding to a prevalence of 103 per 100,000 females; 27.9% had been clinically diagnosed. Females with 47,XXX had taller stature (+6.1 cm, p < 0.001), greater rate of outpatient encounters (p = 0.026), higher odds of kidney disease (odds ratio [OR] = 12.3; 95% confidence interval [CI] 2.9-51.8), glaucoma (OR = 5.1; 95% CI 1.5-13.9), and congestive heart failure (OR = 5.6; 95% CI 1.4-24.2), and were more likely to be unemployed (p = 0.008) with lower annual income (p = 0.021) when compared with 46,XX controls of the same age and genetic ancestry. However, there were no differences in the rates of other encounter types, Charlson Comorbidity Index, all other medical and psychological diagnoses, military service history or quality of life metrics. In conclusion, in this aging and predominately undiagnosed sample, 47,XXX conferred few differences when compared with matched controls, offering a more reassuring perspective to the trisomy X literature., (© 2024 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

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.

Background: Complete molar twin pregnancy with coexisting fetus is a rare and important diagnosis in obstetrics. Preeclampsia, preterm labor and life-threatening vaginal bleeding are the serious complications of this type of pregnancy. Gestational trophoblastic neoplasia should be ruled out after termination of pregnancy. In this study we reviewed a molar twin pregnancy with a live coexisting triple x fetus which has not been reported till now. Case Presentation: Our case was a 22-year-old primigravida woman and 17-18th week of pregnancy, who referred to an University Hospital in Mashhad, Iran with complaint of vaginal bleeding On October 2016. Her first trimester ultrasonography in 13th week of gestational age, reported a live single fetus with an anterior great placenta and cystic formation regarding molar pregnancy. According to above-report, Amniocentesis was done in 15th weeks of pregnancy and its result was triple X. After severe and life-threatening vaginal bleeding, she underwent an emergent hysterotomy. A fetus with no obvious anomaly and a great hydropic and vesicular placenta delivered. Episodic crisis of her blood pressure was best controlled with anti-hypertensive drugs. In our case, chemotherapy with methotrexate was started after poor decline of βHCG titration and definite diagnosis of gestational trophoblastic neoplasia. Remission was completely achieved after four courses of chemotherapy. Conclusion: Differentiation between complete molar pregnancy with live fetus and partial mole is always challenging in obstetrics. Serious complications as preeclampsia and severe vaginal bleeding may become life-threatening. Coexisting molar pregnancy should be ruled out in a pregnancy associated with frequent and unexpectant vaginal bleeding. Amniocentesis and an expert radiologist can help to differentiate them. Following these patients is very important to reveal any trophoblastic neoplasia.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Complete molar twin pregnancy with coexisting fetus is a rare and important diagnosis in obstetrics. Preeclampsia, preterm labor and life-threatening vaginal bleeding are the serious complications of this type of pregnancy. Gestational trophoblastic neoplasia should be ruled out after termination of pregnancy. In this study we reviewed a molar twin pregnancy with a live coexisting triple x fetus which has not been reported till now. Case Presentation: Our case was a 22-year-old primigravida woman and 17-18th week of pregnancy, who referred to an University Hospital in Mashhad, Iran with complaint of vaginal bleeding On October 2016. Her first trimester ultrasonography in 13th week of gestational age, reported a live single fetus with an anterior great placenta and cystic formation regarding molar pregnancy. According to above-report, Amniocentesis was done in 15th weeks of pregnancy and its result was triple X. After severe and lifethreatening vaginal bleeding, she underwent an emergent hysterotomy. A fetus with no obvious anomaly and a great hydropic and vesicular placenta delivered. Episodic crisis of her blood pressure was best controlled with anti-hypertensive drugs. In our case, chemotherapy with methotrexate was started after poor decline of βHCG titration and definite diagnosis of gestational trophoblastic neoplasia. Remission was completely achieved after four courses of chemotherapy. Conclusion: Differentiation between complete molar pregnancy with live fetus and partial mole is always challenging in obstetrics. Serious complications as preeclampsia and severe vaginal bleeding may become life-threatening. Coexisting molar pregnancy should be ruled out in a pregnancy associated with frequent and unexpectant vaginal bleeding. Amniocentesis and an expert radiologist can help to differentiate them. Following these patients is very important to reveal any trophoblastic neoplasia. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Abstract: Background: Children with sex chromosome trisomies (SCT) frequently show problems in language development. However, a clear description of the communicative patterns of these children is still lacking. Aims: To describe the first stages of language development in children with SCT in comparison with those in typically developing (TD) children. The purpose was to verify the existence of possible differences in communicative skills (in both vocal and gestural modality) and identify the presence of possible early predictors (i.e., low vocabulary size and low gesture production) of later language impairment in children with SCT. Methods & Procedures: Fifteen 24‐month‐old children with SCT (eight males with Klinefelter syndrome (KS) and seven females with triple X syndrome (TX)) and fifteen 24‐month‐old TD children (eight males and seven females) participated in the study. Their spontaneous communicative productions were assessed during a semi‐structured play session in interaction with a parent. In addition, their vocabulary size was assessed using a parental report (the Italian version of the MacArthur Communicative Development Inventories). Outcomes & Results: With regards to their vocabulary size, 60% of children with SCT (75% of children with KS and 43% of children with TX) were at risk for language impairments (i.e., they had a vocabulary size smaller than 50 words). In addition, TD children showed better lexical and syntactic skills than children with SCT in their spontaneous communicative productions. However, the production of communicative gestures was higher in children with SCT than in TD children. Boys with KS appeared to differ from TD males in more aspects of communication than girls with TX differed from TD females. Conclusions & Implications: The study showed the importance of early detection of language risk factors in children with SCT, while also considering the use of compensatory strategies (e.g., the use of communicative gestures). [ABSTRACT FROM AUTHOR]

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.

Aim: The effect of a supernumerary X chromosome on bones has not been reported, and this study evaluated bone mineral status and metabolism in nonmosaic 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 nonmosaic triple X syndrome showed significantly reduced AD-SoS (p < 0.005) and BTT Z-scores (p < 0.0001) compared to the control group, and these results persisted when we divided the sample into prepubertal and pubertal patients (p < 0.05). These patients also had significantly reduced ionised calcium (p < 0.005) and 25(OH)D levels (p < 0.005) and higher phosphate (p < 0.0001) and PTH (p < 0.0001) levels.Conclusion: Subjects with nonmosaic triple X syndrome exhibited a significant impairment in bone mineral status and metabolism similar to other X polisomy, such as Klinefelter's syndrome. This suggests the presence of a primary bone deficit and the need for regular and close monitoring of these subjects. [ABSTRACT FROM AUTHOR]

Triple X syndrome (47, XXX) occurs in approximately 1:1,000 female births and has a variable phenotype of physical and psychological features. Prenatal diagnosis rates of 47, XXX are increasing due to non-invasive prenatal genetic testing. Previous studies suggest that prenatal diagnosed females have better neurodevelopmental outcomes. This cross-sectional study describes diagnosis, physical features, medical problems, and neurodevelopmental features in a large cohort of females with 47, XXX. Evaluation included review of medical and developmental history, physical exam, cognitive, and adaptive testing. Medical and developmental features were compared between the prenatal and postnatal diagnosis groups using rate calculations and Fisher's exact test. Cognitive and adaptive tests scores were compared using t-tests. Seventy-four females age 6 months-24 years (mean 8.3 years) participated. Forty-four (59.5%) females were in the prenatal diagnosis group. Mean age of postnatal diagnosis was 5.9 years; developmental delay was the most common indication for postnatal genetic testing. Common physical features included hypertelorism, epicanthal folds, clinodactyly, and hypotonia. Medical problems included dental disorders (44.4%), seizure disorders (16.2%), genitourinary malformations (12.2%). The prenatal diagnosis group had higher verbal ( P < 0.001), general ability index ( P = 0.004), and adaptive functioning scores ( P < 0.001). Rates of ADHD (52.2% vs. 45.5%, P = 0.77) and learning disabilities (39.1% vs. 36.3%, P = 1.00) were similar between the two groups. These findings expand on the phenotypic features in females with Triple X syndrome and support that prenatally ascertained females have better cognitive and functional outcomes. However, prenatally diagnosed females are still at risk for neurodevelopmental disorders. Genetic counseling and treatment recommendations are summarized. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A 31-year-old lady with normal physical characteristics was found to have persistent high FSH and LH and was suspected possible premature ovarian failure after reported to have not normal menstrual cycle. Leucocytes were collected from patient's fresh peripheral blood sample and Giemsa banding (G-banding) was done. All metaphases were captured and analysed using Cytovision software 4.5 and the final analysis show 47,XXX. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome.Design: Cross-sectional study with retrospective analysis.Setting: University pediatric hospital.Patient(s): Fifteen prepubertal subjects (median age 9.0 years, range 6.9-11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9-11.6 years).Intervention(s): None.Main Outcome Measure(s): We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test.Result(s): All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients.Conclusion(s): Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate cytogenetic findings in Omani patients who had been referred for suspicion of sex chromosome abnormalities that resulted in different clinical disorders. Furthermore, it sought to examine the frequency of chromosomal anomalies in these patients and to compare the obtained results with those reported elsewhere. Cytogenetic analysis was performed on 1232 cases with variant characteristics of sexual development disorders who had been referred to the cytogenetic department, National Genetic Centre, Ministry of Health, from different hospitals in the Sultanate of Oman between 1999 and 2014. The karyotype results demonstrated chromosomal anomalies in 24.2% of the cases, where 67.5% of abnormalities were identified in referral females, whereas only 32.6% were in referral males. Of all sex chromosome anomalies detected, Turner syndrome was the most frequent (38.2%) followed by Klinefelter syndrome (24.9%) and XY phenotypic females (16%). XXX syndrome and XX phenotypic males represented 6.8% and 3.8% of all sex chromosome anomalies, respectively. Cytogenetic analysis of patients referred with various clinical suspicions of chromosomal abnormalities revealed a high rate of chromosomal anomalies. This is the first broad cytogenetic study reporting combined frequencies of sex chromosome anomalies in sex development disorders in Oman. [ABSTRACT FROM AUTHOR]