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Background: 48, XXYY syndrome is a rare sex chromosome aneuploidy with severe systemic features. Ophthalmic manifestation of 48, XXYY syndrome include hypertelorism, epicanthic folds, hooded eye lids, strabismus, retinitis pigmentosa and Duane's syndrome., Case: We present mild foveal hypoplasia in a 12-year-old boy with 48, XXYY syndrome using swept-source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The boy was referred for assessment of strabismus and poor visual acuity. OCT revealed persistence of inner retinal layers, and thinning of the outer nuclear layer in the perifoveal region with thickening of the outer plexiform layer. OCTA revealed increased vessel density with reduced foveal avascular zone., Conclusion: We described novel OCT and OCTA features of bilateral foveal hypoplasia and reduction of FAZ in a case of 48, XXYY syndrome based on detailed clinical observation and thorough genetic testing. This case expanded the current literature of this rare sex chromosome abnormality and suggest the importance of retinal examinations in 48, XXYY syndrome.

Sex chromosome disorders severely compromise gametogenesis in both males and females. In oogenesis, the presence of an additional Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes 1-5 . Here we efficiently converted the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells. In addition, this chromosomal alteration successfully eradicated trisomy 16, a model of Down's syndrome, in PS cells. Artificially produced euploid XX PS cells differentiated into mature oocytes in culture with similar efficiency to native XX PS cells. Using this method, we differentiated induced pluripotent stem cells from the tail of a sexually mature male mouse into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could ameliorate infertility caused by sex chromosome or autosomal disorders, and opens the possibility of bipaternal reproduction., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Some non-factor products that work by facilitating the coagulation pathway (emicizumab) and blocking the anticoagulant pathway (fitusiran, concizumab and marstacimab) for patients with haemophilia (H) have been developed, and clinical trials using these products are currently ongoing. Prophylaxis using non-factor products by subcutaneous administration provides marked reductions of bleeding episodes in patients with HA or HB, regardless of the presence of inhibitor. Emicizumab has already been approved globally. Emicizumab alters the phenotype of patients with HA from severe to mild by maintaining trough levels of equivalent factor VIII activity (15-20 iu/dl). Phase 3 clinical trials and long-term observations assessing emicizumab revealed tolerable safety and efficacy. However, thrombotic events have occurred in patients receiving these non-factor products. Furthermore, monitoring of the haemostatic function of these products with concomitant therapy is also required in clinical practice. These products have promising haemostatic efficiency, but wider clinical experience is needed to provide optimal therapeutic strategies in the future., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Although language difficulties are one of the most distinctive characteristics of the neuropsychological profile of children with sex chromosome trisomies (SCT), the analysis of the maternal input addressed to them is a neglected topic., Aims: The present study aims to analyse the lexical, morphosyntactic, and functional features of the input addressed to children with SCT comparing them with those of the input directed to typically developing children (TD)., Methods & Procedures: Participants were 38 mothers and their 8-month-old children, 19 with SCT and 19 TD children. Maternal utterances, collected during video-recorded play sessions, have been transcribed and coded., Outcomes & Results: No significant differences between groups have been found in the lexical and syntactic characteristics of maternal input. However, considering the input functional features, the proportion of directives and questions was significantly higher in the maternal input addressed to children with SCT than in the input addressed to TD children whereas the opposite pattern was found in the proportion of affect-salient speech., Conclusions & Implications: The awareness of a possible delay in their children's language development could influence the way the mothers speak to them. In particular, the functional features of maternal input could be affected. Support groups for parents of children with SCT at the preverbal stage could be useful to reassure the mothers about their role in their children's language development. What this paper adds What is already known on the subject Studies in the literature identified a high percentage of language delays or impairments in children with SCT. To date, according to our knowledge, there are no studies that analyse the linguistic input addressed to these children. What this study adds The lexical and syntactic features of maternal input addressed to 8-month-old children with SCT are adequate to the children's communicative skills. However, the mothers of children with SCT seem to provide additional scaffolding in their verbal input, using a lower proportion of affect-salient speech and a higher proportion of questions. In addition, a higher proportion of directives suggests the use of a more demanding style. Clinical implications of this study The awareness of possible language delays could influence the functional features of input leading mothers to use a more supportive and demanding input. Support groups for parents of children with SCT at the preverbal stage could be useful to reassure the mothers about their role in their children's language development., (© 2020 Royal College of Speech and Language Therapists.)

Rationale: The karyotype 49,XXXXY is a rare form of Klinefelter syndrome usually presenting with ambiguous genitalia, facial dysmorphism, mental retardation, and a combination of cardiac, skeletal, and other malformations., Patient Concerns: We describe a 19-year-old man, whose chromosomal analysis of peripheral blood revealed a karyotype of 49,XXXXY. His mental development and motor ability were significantly delayed. At the age of 19, he had failed to develop secondary sexual characteristics. His random blood glucose level was 19.61 mmol/L, and he showed dry mouth, polydipsia, and polyuria. He had a characteristic facial appearance with prognathism, widened nasal bridge, and strabismus. His bilateral elbow rotation was limited. He had atrophic testes with micropenis. Ophthalmic examination revealed a polar cataract in both eyes., Diagnosis: He was diagnosed with Klinefelter syndrome associated with cleft palate, hypothyroidism, cataracts, diabetes, and other anomalies., Interventions: After the initial diagnosis, the patient received intensive insulin therapy to correct hyperglycemia, and he received calcium and vitamin D supplements. The patient also received testosterone and thyroid hormone replacement therapy for primary hypogonadism., Outcomes: The patient was discharged 12 days after receiving treatment; meanwhile, there were no clinical symptoms of dry mouth, polyuria and polyuria, and his blood glucose level was controlled., Lessons: The combination of cleft palate, hypothyroidism, cataracts, diabetes, and osteoporosis in 49,XXXXY syndrome has not yet been reported. Early treatment and appropriate care can significantly improve the patient's quality of life and prevent serious consequences.

47,XYY syndrome (XYY) is a male sex chromosome disorder where individuals have an X chromosome and two copies of the Y chromosome. XYY is associated with a physical phenotype and carries increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Latencies of auditory evoked responses measured by magnetoencephalography have shown atypical prolongations in several neuropsychiatric and genetic disorders; specifically, delayed auditory responses have been observed in ASD. In this study, we investigated the associations of genotype and clinical phenotype with auditory processing. Whole cortex magnetoencephalography recorded during a passive auditory paradigm (500 Hz tones) was used to assess the auditory evoked response in three groups of male children: idiopathic ASD, typically developing, and XYY boys. Response waveforms were computed for left and right auditory cortex and latencies of the ∼50 ms (M50) and ∼100 ms (M100) components were determined. M50 latencies were significantly delayed compared with typically developing controls in children with ASD in the right hemisphere only, and in children with XYY in the left hemisphere only, irrespective of whether they met diagnostic criteria for ASD. Findings on the later M100 component trended in the same directions but did not attain significance, due to increased variance. Replicating previous findings, decreased M50 and M100 latencies with age were observed bilaterally. Overall, while XYY shares an electrophysiological phenotype (delayed evoked response latency) with idiopathic ASD, the hemispheric differences warrant further investigation.

47,XYY syndrome (XYY) is one of the common forms of sex chromosome aneuploidy in males. XYY males tend to have tall stature, early speech, motor delays, social and behavioral challenges, and a high rate of language impairment. Recent studies indicate that 20-40% of males with XYY meet diagnostic criteria for autism spectrum disorder (ASD; the rate in the general population is 1-2%). Although many studies have examined the neural correlates of language impairment in ASD, few similar studies have been conducted on individuals with XYY. Studies using magnetoencephalography (MEG) in idiopathic ASD (ASD-I) have demonstrated delayed neurophysiological responses to changes in the auditory stream, revealed in the mismatch negativity or its magnetic counterpart, the mismatch field (MMF). This study investigated whether similar findings are observed in XYY-associated ASD and whether delayed processing is also present in individuals with XYY without ASD. MEG measured MMFs arising from the left and the right superior temporal gyrus during an auditory oddball paradigm with vowel stimuli (/a/ and /u/) in children/adolescents with XYY both with and without a diagnosis of ASD, as well as in those with ASD-I and in typically developing controls (TD). Ninety male participants (6-17 years old) were included in the final analyses (TD, n = 38, 11.50 ± 2.88 years; ASD-I, n = 21, 13.83 ± 3.25 years; XYY without ASD, n = 15, 12.65 ± 3.91 years; XYY with ASD, n = 16, 12.62 ± 3.19 years). The groups did not differ significantly in age (p > 0.05). There was a main effect of group on MMF latency (p < 0.001). Delayed MMF latencies were found in participants with XYY both with and without an ASD diagnosis, as well as in the ASD-I group compared to the TD group (ps < 0.001). Furthermore, participants with XYY (with and without ASD) showed a longer MMF latency than the ASD-I group (ps < 0.001). There was, however, no significant difference in MMF latency between individuals with XYY with ASD and those with XYY without ASD. Delayed MMF latencies were associated with severity of language impairment. Our findings suggest that auditory MMF latency delays are pronounced in this specific Y chromosome aneuploidy disorder, both with and without an ASD diagnosis, and thus may implicate the genes of the Y chromosome in mediating atypical MMF activity., (© 2019 S. Karger AG, Basel.)

Background: XYY syndrome is a sex chromosome aneuploidy that occurs in ~ 1/850 male births and is associated with increased risk for neurodevelopmental difficulties. However, the profile of neurodevelopmental impairments, including symptoms of autism spectrum disorder (ASD) in XYY remains poorly understood. This gap in knowledge has persisted in part due to lack of access to patient cohorts with dense and homogeneous phenotypic data., Methods: We evaluated a single-center cohort of 64 individuals with XYY aged 5-25 years, using a standardized battery of cognitive and behavioral assessments spanning developmental milestones, IQ, adaptive behavior, academic achievement, behavioral problems, and gold-standard diagnostic instruments for ASD. Our goals were to (i) detail the neurodevelopmental profile of XYY with a focus on ASD diagnostic rates and symptom profiles, (ii) screen phenotypes for potential ascertainment bias effects by contrasting pre- vs. postnatally diagnosed XYY subgroups, and (iii) define major modules of phenotypic variation using graph-theoretical analysis., Results: Although there was marked inter-individual variability, the average profile was characterized by some degree of developmental delay, and decreased IQ and adaptive behavior. Impairments were most pronounced for language and socio-communicative functioning. The rate of ASD was 14%, and these individuals exhibited autism symptom profiles resembling those observed in ASD without XYY. Most neurodevelopmental dimensions showed milder impairment among pre- vs. postnatally diagnosed individuals, with clinically meaningful differences in verbal IQ. Feature network analysis revealed three reliably separable modules comprising (i) cognition and academic achievement, (ii) broad domain psychopathology and adaptive behavior, and (iii) ASD-related features., Conclusions: By adding granularity to our understanding of neurodevelopmental difficulties in XYY, these findings assist targeted clinical assessment of newly identified cases, motivate greater provision of specialized multidisciplinary support, and inform future efforts to integrate behavioral phenotypes in XYY with neurobiology., Trial Registrations: ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls."

Case Report: The case concerns a 16 year-old boy with a history of high myopia and unilateral congenital cataract, tall stature for age, facial dysmorphism, hypermobile metacarpal-phalangeal joints, as well as behavioural problems. The mother had a history of recurrent pregnancy loss. Chromosomal analysis of the peripheral blood lymphocytes reported 47,XYY., Discussion: Patients with sex chromosome aneuploidy 47,XYY have higher risk of congenital malformations, although ophthalmological anomalies are unusual. Evaluation of patients with tall stature and behavioural problems should include a chromosomal analysis in order to determine the aetiology., (Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Isodicentric Y chromosome [idic(Y)] represents a relatively common subtype of Y chromosomal rearrangements in the germline; however, limited evidence supports the postzygotic occurrence of idic(Y). Here, we report a boy with hypospadias and somatically acquired idic(Y). The 3.5-year-old boy has been identified in our previous study for patients with hypospadias. In the present study, cytogenetic analysis including FISH revealed a 45,X[5]/46,X,idic(Y)[7]/46,XY[8] karyotype. MLPA showed a mosaic deletion involving PPP1R12BP1 and RBMY2DP. The idic(Y) was likely to have been formed through aberrant recombination between P1 palindromes and subsequently underwent mosaic loss. The patient's phenotype was attributable to deletion of some Y chromosomal genes and/or mosaic loss of chromosome Y (mLOY). The results suggest that idic(Y) can originate in postzygotic cells via palindrome-mediated crossovers. Moreover, our data indicate that somatically acquired idic(Y) can trigger mLOY, which usually appears as an aging-related phenomenon in elderly men., (© 2018 S. Karger AG, Basel.)

Sex chromosome abnormalities are among the most common genetic changes. The manifestations vary and may include growth abnormalities, specific appearance features, and other endocrinological and physical disorders, but also delayed psychomotor development, learning disabilities, and psychiatric conditions including ADHD and autism spectrum disorders. Increased knowledge about the relationship between sex chromosome abnormalities, development and psychiatric conditions would enable improved care of these patients.

Known genetic alterations play a major role in perturbing male reproductive health. We sought to retrospectively validate the European Association of Urology (EAU) guidelines for karyotype analysis (KA) in a homogenous cohort of 1168 White European men presenting for primary couple's infertility (noninterracial infertile couples only) and to develop a novel nomogram capable of predicting karyotype alterations. Overall, 742 (63.5%) patients would have deserved KA according to the EAU guidelines. Of those, 48 (6.9% of the assessable patients according to EAU guidelines) displayed any kind of alteration at KA. Conversely, hypothetically relying on the EAU criteria, 12 (20%) out of 60 patients with karyotype abnormalities would not have been candidates for the same genetic assessment. Overall, 694 (62.6%) patients would have been candidates for genetic workup despite having a normal karyotype. As a whole, the EAU guideline sensitivity, specificity, and discrimination were 80%, 37%, and 59%, respectively. We developed a novel nomogram, with a 2% probability cut-off, which allows for a more careful detection of KA alterations., Patient Summary: The application of the European Association of Urology guidelines for karyotype analysis does not ensure an adequate diagnostic process. In this regard, we propose a novel diagnostic tool to improve detection of alterations at karyotype analysis., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Periventricular nodular heterotopia (PNH) with overlying polymicrogyria (PMG) is a recently described, developmental brain malformation; however, the causative genes of this malformation have not yet been identified. We report on a 5-year-old Japanese male with bilateral PNH with overlying PMG. He had mild intellectual disability, distinctive facial features, short stature, and microcephaly, with cardiac disorders. No mutation was identified in Sanger sequences for FLNA and ARFGEF2; however, array comparative genomic hybridization revealed an approximately 0.8Mb gain at Xq26.1-26.2, which included three genes: IGSF1, OR13H1, and FIRRE. We identified the same 3-copy gain in his mother; despite identifying the same abnormality in the mother, it must still be considered as a possible cause for the abnormalities, as X-inactivation in the mother could have led to her not expressing the same phenotype. This case may provide important clues for identifying the genes responsible and help in the understanding of the pathogenesis of this disorder., (© 2014 Mac Keith Press.)

Numerical abnormalities of sex chromosomes are seen approximately 1 in 400 live births. Pentasomy X is a very rare chromosomal abnormality and it is defined as presence of five X chromosomes instead of two. Prenatal sonographic features have rarely been described in the literature before. Here we present a non-immune fetal hydrops diagnosed during the 17th week of gestation. Ultrasonographic examination revealed subcutaneous edema, pleural effusion and ascites, and also clinodactyly of the fifth fingers of both hands. The fetal karyotype was assessed as 49,XXXXX (pentasomy X) in two different culture flasks. Hydropic signs regressed at 21 weeks' gestation. Prenatal diagnosis may not be possible usually for this rare chromosomal abnormality. Every anomaly detected prenatally, such as transient hydrops, may help us to diagnose pentasomy X., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Background:  Supernumerary sex chromosome aneuploidies (X/Y-aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of children with tri-, tetra-, and pentasomy X/Y-aneuploidy. The current research sought to fill this gap in the literature and to examine dosage effects of X and Y chromosomes on language and social functioning., Methods: Participants included 110 youth with X/Y-aneuploidies (32 female) and 52 with typical development (25 female) matched on age (mean ∼12 years; range 4-22) and maternal education. Participants completed the Wechsler intelligence scales, and parents completed the children's communication checklist-2 and the social responsiveness scale to assess language skills and autistic traits, respectively., Results: Both supernumerary X and Y chromosomes were related to depressed structural and pragmatic language skills and increased autistic traits. The addition of a Y chromosome had a disproportionately greater impact on pragmatic language; the addition of one or more X chromosomes had a disproportionately greater impact on structural language., Conclusions: Given that we link extra X chromosomes with structural language impairments and an extra Y chromosome with pragmatic language impairments, X/Y-aneuploidies may provide clues to genetic mechanisms contributing to idiopathic language impairment and autism spectrum disorders., (© 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.)

Chromosome X-to-autosome translocations [t(X;A)] are rare rearrangements with an estimated occurrence of 1 to 3 per 10,000 live births. Occurrences of Xq duplications have been observed in male and female subjects in whom the X chromosome segment escapes inactivation and results in functional disomy. We report a case of X;6 translocation in a 7-year-old boy with severe mental retardation, hypotonia, and recurrent respiratory tract infections. High-resolution chromosome analyses (fluorescence in situ hybridization, multiplex ligation probe-dependent amplification, and whole-genome array) revealed a terminal duplication of chromosome X at q28-qter (approximately 3.246 Mb in size) involving gene MECP2 and a terminal deletion (approximately 1.89 Mb) with the breakpoint at 6q27. This is the second report of a boy with a cryptic unbalanced Xq-autosome translocation. This case increases our understanding of mental disability caused by terminal Xq duplication., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Unlabelled: The clinical and laboratory features as well as the diagnostic and therapeutic approach of men with XYY syndrome have not been fully described. A 41-year-old infertile man was diagnosed as having a 47,XYY karyotype and a micro-prolactinoma. His 32-year-old wife had a history of five spontaneous pregnancies, all resulting in first trimester miscarriages. Three in-vitro fertilization (IVF) attempts were made with no biochemical pregnancy. During the third attempt, a pre-implantation genetic diagnosis (PGD) was performed by fluorescent in-situ hybridization (FISH) technique. Only one out of six (16%) embryos had normal karyotype., Conclusions: (1) Karyotypic analysis of both partners is a sine qua non investigation for recurrent miscarriages; (2) the XYY syndrome results in high frequency of embryo aneuploidy; (3) PGD by FISH can contribute to the transferring of chromosomally normal embryos in cases of parental chromosomal defects; (4) investigation for a prolactinoma should be considered in men with XYY syndrome.

Cytogenetic investigations are performed in couples asking for IVF or intracytoplasmic sperm injection (ICSI) treatment. These serve a diagnostic purpose because male or female infertility might have a chromosomal origin. Chromosomal aberrations found in these patients include numerical abnormalities, such as Klinefelter syndrome, XYY karyotype or Turner syndrome and its variants; sex reversions, such as XX males or XY females; and also structural abnormalities, such as Robertsonian or reciprocal translocations and inversions. Finding the chromosomal origin of infertility in a patient also has a prognostic value because it aids the management of pregnancies obtained after IVF or ICSI and may lead to a proposal of prenatal or preimplantation genetic diagnosis.

Background: Epignathus is a rare form of congenital teratoma, originating from the base of the skull, most commonly the hard palate, or mandible. It has been associated with a poor prognosis due to complications including polyhydramnios and respiratory compromise at birth as a consequence of upper airway obstructions. It is usually not associated with chromosomal aberrations. We present a case of prenatally diagnosed epignathus associated with a gonosomal pentasomy 49,XXXXY., Case: A 34-year-old gravida 1, para 0 was referred to our unit with a sonographically suspected gastroschisis at 26+6 weeks' gestation. A detailed ultrasound scan revealed a large mixed echogenic mass seen in continuation with the mouth in the midline. Based on the appearance, an epignathus was suspected. No other fetal anomalies were detected. Karyotyping showed a 49,XXXXY karyotype of the fetus. The couple decided to continue the pregnancy after detailed counseling about results and prognosis. A cesarean section was necessary and performed at 29+0 weeks' gestation due to a pathological Doppler and cardiotocogram. Because of the enormous epignathus intubation of the newborn was not possible. A tracheostomy was performed for ventilation and oxygenation, which failed and the newborn died 30 min after birth., Conclusion: Prenatal diagnosis by ultrasound has improved perinatal management. This should include assessment of the tumor size and spread in order to establish an accurate prognosis and to anticipate likely problems which are to be encountered during pregnancy or at the time of delivery. To our knowledge, this is the first reported case of a prenatally diagnosed epignathus with a gonosomal pentasomy 49,XXXXY., (Copyright 2008 S. Karger AG, Basel.)

Objective: Isolated nonvisualized fetal gallbladder (INVFGB) is relatively rare. In most cases, the gallbladder will eventually be detected. In some cases however, INVFGB may be associated with serious abnormalities, cystic fibrosis (CF), aneuploidy, and agenesis of the gall bladder. We describe a clinical evaluation of prenatally diagnosed INVFGB., Methods: Cases of nonvisualized gallbladder were first evaluated by serial scans. Cases with no additional malformations were designated as INVFGB, and were further evaluated by mutation analysis for CF, and amniocentesis for karyotype and microvillar membrane enzymes (MME)., Results: A total of 22 cases of nonvisualized gallbladder were detected. Of these, 2 had additional malformations, and 3 were excluded because of incomplete evaluation. Of the remaining 17 cases, 3 (17.6%) had adverse outcomes: 1 case of CF, 1 case of 47,XXX, and 1 case of multiple congenital anomalies detected only postnatally. Abnormal levels of MMEs were detected in 3 cases, 1 of which was diagnosed with CF. In 2 cases, the gallbladder was not detected even after birth, but development is normal., Conclusion: Evaluation of INVFGB should include genetic counselling, amniocentesis for karyotype and MME analysis, CFTR mutation analysis and repeated ultrasound scans., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

Genes for reproduction are enriched on the sex chromosomes and they may be involved in the many forms of X- or Y-linked infertility. Here we review the X-linked disorders of ovulation and we show that despite the relatively frequent observation of X chromosome rearrangements in women with ovarian dysgenesis or ovarian failure, the search for X-linked genes has not yet been very fruitful: only two genes have been demonstrated definitively, BMP15 and FMR1. However, the size of the rearrangements and the characteristics of some of the genes suggest that many of the X-linked genes only rarely may be causative and more frequently they may represent risk factors for premature ovarian failure (POF) and will have to be identified by specific approaches. Moreover, recent data seem to suggest a structural and novel role for the X chromosome in some of the POF rearrangements, and also that X-linked POF is not always dependent from the presence of X-linked genes.

Objective: To present an overview of the potential etiologies of premature ovarian failure (POF), with an emphasis on the chromosomal abnormalities, gene mutations and autoimmune disorders., Study Design: This article is based on a literature review of articles on POF using PubMed and MEDLINE for the years 1966-2005 using the keywords premature ovarian failure, trying to ascertain the possible mechanisms of POF reported to date., Results: The etiology of POF is still under investigation, even though a wide range of etiologies has been unveiled, encompassing genetic mutations, chromosomal abnormalities, autoimmune disorders, and iatrogenic (irradiation, chemotherapy) and idiopathic causes., Conclusion: In the majority of POF cases, the etiology remains subtle.

The acquired mutation Val617Phe in the tyrosine kinase JAK2 was recently identified in most but not all patients with classical myeloproliferative disorders. We describe a cytogenetic and molecular study of a JAK2Val617Phe-negative case of essential thrombocythemia harboring the acquired translocation t(X;5)(q13;q33). We show that this involves the inactive X-chromosome and is associated with silencing of autosomal genes within the adjacent 5q minus syndrome common deleted region. This is the first documented example of autosomal gene silencing adjacent to an X-autosome breakpoint in human malignancy and such a mechanism may underlie the pathogenesis of related disorders with translocations involving Xq13.

Introduction: Nowadays more and more couples face the fact that they cannot have babies in spite of many years of trying. The male factor can be identified in about half of these cases., Aim: The aim of this study was to analyse chromosomal alterations in patients with azoospermia. These patients may be candidates for testicular sperm retrieval and intracytoplasmatic sperm injection., Materials and Methods: Preoperative evaluation included routine andrological investigation with 2 semen analysis, ultrasound, hormonal and genetic examination. Traditional histological examination and embryological diagnostic of tissue samples was performed. Cryopreservation of retrieved testicular tissue was also done. Between January 2001 and June 2005 73 biopsies were performed in 71 patients for testicular sperm extraction. In order to obtain an exact diagnosis, the traditional cytogenetic methods and fluorescence in situ hybridization analyses were performed in combination with molecular genetic techniques. Patients were offered to participate in the assisted reproduction programme on the base of their genetic results., Results: In this study, the most characteristic cases were numerical deviations, such as 47,XXY (2 cases), mosaic 47,XXY/49,XXXXY (1 case), 47,XYY (1 case) and mosaic 46,XY/45,X (1 case) karyotypes. Non-obstructive azoospermia was diagnosed in 53 patients (79%)., Conclusions: Authors emphasised the importance of cyto- and molecular examinations in cases of genetical disorders. The results provide a chance for patients to be spared from long-drawn moreover psychological burdening examinations. In addition the costs of different clinical intervention could be saved too.

Thrombolytic therapy is a well-defined treatment option for arterial and venous thrombosis in adults. In contrast, uniform recommendations regarding the indication, route of administration, and dosing of thrombolytic therapy in children are not available. The authors report the successful resolution of bilateral pulmonary embolism and popliteal artery thrombosis in an 11-year-old girl and 13-year-old girl, respectively, by catheter-directed thrombolysis with low-dose recombinant tissue plasminogen activator. Catheter-directed low-dose thrombolysis is an efficient treatment option for severe venous and arterial thrombosis in children.

The 49, XXXXY syndrome was first reported in 1960. It represents a rare sex chromosome aneuploidy syndrome. Some consider it as the most severe variant of Klinefelter syndrome (47, XXY). The approximate incidence is 1 in 85,000 male births. The karyotype arises from maternal non-disjunction during both meiosis I and meiosis II. The clinical presentations of 49, XXXXY syndrome include mental deficiency, hypogonadism, severe speech delay, multiple skeletal anomalies, cardiac defects and characteristic facial features. It might be mistaken for Down syndrome and needs chromosome analysis for confirmation. According to literature review, urinary tract anomaly in association with 49, XXXXY syndrome was extremely rare. Here we report a case of 49, XXXXY with Down syndrome-like facial dysmorphism, who was found to have patent ductus arteriosus and hypotonia. Moreover, he also got grade V vesico-ureteral reflux, R't with hydronephrosis and urinary tract infection. We hope to remind clinicians to arrange chromosomal analysis if multiple congenital anomalies exist in a neonate. And remember to exclude congenital genitourinary tract anomaly if karyotype 49, XXXXY is diagnosed.

Aortic insufficiency is not a part of the hypoplastic left heart syndrome. This report describes a rare case of congenital aortic insufficiency from a detached leaflet in a patient with hypoplastic left heart syndrome and 45,X/46XY mosaicism. The patient was subsequently treated with the modified Norwood procedure along with suture closure of aortic valve.

Although epilepsy and mental retardation are commonly observed in individuals with chromosomal aberrations, the identification of EEG/epileptic profiles in those with specific chromosome anomalies remains difficult. A few syndromes seem to show peculiar clinical and EEG associations. The authors report an electroclinical investigation on a group of patients carrying X chromosome anomalies: 16 patients with Turner's syndrome, 17 with Klinefelter's syndrome, 1 with an X-autosomal rearrangement, 2 with Xq isochromosome [Xq(i)], and 7 with triple X syndrome. Epilepsy and/or EEG anomalies were found in three of the patients with Klinefelter's syndrome, in one patient with an X-autosomal rearrangement, and in five of those with triple X syndrome. No epilepsy or EEG anomalies were detected in the other patients. Epilepsy may be associated with Klinefelter's syndrome. In addition, the authors found that an electroclinical pattern, represented by paroxysmal activity in the posterior regions (temporo-parieto-occipital areas) with complex partial seizures and easily controlled by antiepileptic drugs, may be present in patients with triple X syndrome. In contrast, gross X-autosomal rearrangements are associated with polymorphic EEG/epileptic findings. Although further studies are needed to validate these observations, they clearly confirm the strict relationship between X chromosome anomalies and epilepsy.

49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome characterized by mental retardation, severe speech impairment, craniofacial abnormalities, multiple skeletal defects, and genital abnormalities. We describe a 13-year-old boy with 49,XXXXY syndrome, language impairment, seizures, and left-hemisphere magnetic resonance imaging abnormalities and review the distinctive neurologic, cognitive, and behavioral phenotypes associated with this disorder. Finally, we discuss testosterone supplementation in the treatment of this syndrome.