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Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX., (© 2024 Wiley Periodicals LLC.)

Turner syndrome (TS), caused by complete or partial loss of the second sex chromosome, is associated with complex medical manifestations. The TS community identifies anxiety as a major contributor to reduced quality of life. The study aimed to improve understanding of anxiety symptomatology, diagnosis, and care in individuals with TS. A mixed methods design integrated community engagement, including community leaders as co-investigators and a community advisory board, an online survey (N = 135), and in-depth interviews (N = 10). The majority of respondents reported that anxiety symptoms occur two or more days per week, with self-advocates reporting more frequent symptoms than caregivers (p = 0.03). Self-advocates reported feeling anxious more often at school/work; both rater groups reported anxiety-related behaviors were most likely to be expressed at home. Insomnia was the most common symptom of anxiety endorsed across age and rater groups (>70%). Anxiety symptoms and triggers changed with age and often were undiagnosed or untreated during childhood. Therapy and medication were reported as helpful by most respondents who had tried these strategies. Qualitative themes included: 'Triggers for anxiety are related to TS', 'Anxiety impacts the whole family', and 'Opportunities for early identification and intervention'., (© 2024 Wiley Periodicals LLC.)

Sex chromosome trisomies (SCTs) are characterized by an extra X- or Y-chromosome (XXX, XXY, XYY). The present study aims to investigate early signs of social communication and social emotional development in very young children with SCT. Thirty-four children with SCT (aged 12-24 months) were included in this study, as well as 31 age-matched controls. Social communication was measured with structured behavior observations according to the Early Social Communication Scales, and social emotional developmental level with the Bayley Social Emotional parental questionnaire. Recruitment and assessment took place in the Netherlands and in the United States. On average, 12-24-month old children with SCT showed difficulties with early social communication, more so in responding to others as compared to initiating social communications. During social interactions, children with SCT made less frequent eye contact, compared to controls. Also, difficulties in acquiring social emotional milestones were found in 1-year old children with SCT, with 44% of the children having social emotional vulnerabilities in the borderline or extremely low range, compared to typically developing children. In this cohort, no significant predictive effects of karyotype-subtype (XXX, XXY, XYY) were found. Already from a very early age, SCT can be associated with increased risk for vulnerabilities in adaptive social functioning. These findings suggest that SCT impact the maturation of the social brain already from an early age, and stress the importance of early monitoring and (preventive) support early social development in young children with SCT., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Individuals with sex chromosome trisomies ([SCT], XXX, XXY, and XYY)) are at increased risk for neurodevelopmental problems, given that a significant portion of the sex chromosome genes impact brain functioning. An elevated risk for psychopathology has also been described, including attention deficit-hyperactivity disorder (ADHD). The present study aimed at identifying early markers of ADHD, providing the first investigation of ADHD symptomology in very young children with SCT. The variety, type, and severity of ADHD symptomology in 1-6-year-old children with SCT (n = 104) were compared with population-based controls (n = 101) using the strengths and weaknesses of ADHD symptoms and normal-behavior (SWAN) parent-report questionnaire. ADHD symptomology was significantly more prevalent in SCT and already present from toddlerhood on, compared to controls. ADHD inattention symptoms were significantly increased in all karyotypes (XXX, XXY, and XYY), boys with XYY also showed significantly more hyperactivity/impulsivity symptoms than controls. Inattentiveness was more pronounced with increasing age for SCT, in contrast to controls. Within the SCT group, 24% of the children had significantly elevated ADHD symptoms at a clinical level. Already from an early age on, SCT is associated with a risk for ADHD, suggesting that its neurodevelopmental risk lies anchored in early brain maturation. Studying this genetically vulnerable population allows for the prospective study of risk markers to facilitate early and preventive interventions., (© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: Obesity is a risk factor for non-alcoholic steatohepatitis (NASH) and increases the risk of several cancer types including cancers of the liver. Bariatric surgery can provide durable weight loss, but little is known about the later development of hepatocellular carcinoma (HCC) after surgery., Aim: To determine whether bariatric surgery reduces the risk of HCC., Methods: We performed a comprehensive literature search of major databases (from inception to November 2020) to identify studies which assess the incidence and risk of HCC following bariatric surgery. Pooled data were assessed using a random-effects model expressed in terms of odds ratio (OR), incidence rate ratio and 95% confidence interval (CI)., Results: Nine studies (two abstracts and seven full texts) were included for meta-analysis which involved 19 514 750 patients (18 423 546 controls and 1 091 204 bariatric patients). Pooled unadjusted odds ratio (OR) was 0.40 (95% CI: 0.28-0.57) which favoured bariatric surgery, though with high heterogeneity (I 2 : 79%). Using an adjusted model derived from matched cohorts (five studies) yielded an OR of 0.63 (95% CI: 0.53-0.75) with moderate heterogeneity (I 2 : 38%). The pooled rate/1000 person-years was 0.05 (95% CI: 0.02-0.07) in bariatric surgery patients and 0.34 (95% CI: 0.20-0.49) in the control group with an incidence rate ratio of 0.28 (95% CI: 0.18-0.42)., Conclusion: Bariatric surgery is associated with a decreased risk of HCC., (© 2021 John Wiley & Sons Ltd.)

Few studies have systematically assessed executive functioning (EF) skills in boys with XXY, and these are limited by small samples and restricted EF assessment. This study used a broader battery of performance-based measures as well as parent-rating scales of EF in 77 boys and adolescents with XXY (mean age = 12.5 years), recruited from a clinical trial and an outpatient clinic. Exploratory factor analyses were used to create EF domains from performance-based measures, and similar domains were measured using the Behavior Rating Inventory of Executive Function and Conners Parent-Rating Scales. The boys with XXY showed a distinct EF profile, with the greatest deficit in attention and more moderate deficits in working memory, switching, and planning/problem solving. Parent ratings showed similar challenges, as well as impaired inhibition. Independent sample t-tests showed no difference on performance measures between boys diagnosed or not diagnosed with attention-deficit/hyperactivity disorder (ADHD), although parents of boys diagnosed with ADHD reported more difficulties. There were no differences on performance-based tests between those diagnosed pre- and postnatally, although parents of postnatally diagnosed boys reported more metacognitive problems. Language deficits, cognition, and socio-economic status did not account for EF deficits., (© 2020 Wiley Periodicals LLC.)

Children with SCT have an increased risk of suboptimal neurodevelopment. Previous studies have shown an elevated risk for neurobehavioral problems in individuals with SCT. However, not much is known about neurobehavioral problems in very young children; knowledge that could help with early identification of children at risk for suboptimal development, and that could help establish targets for early intervention. This study addressed the question of what the behavioral profile of children with SCT aged 1-5 years looks like. In total, 182 children aged 1-5 years participated in this study (N SCT =87, N nonclinical controls = 95). Recruitment and assessment took place in the Netherlands and the United States. The SCT group was recruited through prospective follow-up (50%), information seeking parents (31%), and clinical referral (18%). Behavioral profiles were assessed with the child behavior checklist and the ages-and-stages social-emotional questionnaire. Levels of parent-rated problem behavior were higher in children with SCT. Difficulties with overall social-emotional functioning were already present in 1-year-olds, and elevated scores were persistent across the full age range. Affective and pervasive developmental behaviors were seen in late toddlerhood and prominent at preschool age. Anxiety, attention deficit, and oppositional defiant behaviors were seen in preschool-aged children. Within this cross-sectional study, the developmental trajectory of affective, pervasive developmental, and oppositional defiant behaviors seemed to be different for SCT children than nonclinical controls. Collectively, these results demonstrate the importance of behavioral screening for behavioral problems in routine clinical care for children with SCT from a young age. Social-emotional problems may require special attention, as these problems seem most prominent, showing increased risk across the full age range, and with these problems occurring regardless of the timing of diagnosis, and across all three SCT karyotypes., (© 2020 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals, Inc.)

Sex chromosome aneuploidies (SCAs) are the most commonly occurring aneuploidies in children with a collective prevalence rate of 1 in 500 live births. Prior research has documented SCAs are associated with an increased risk for early expressive language and gross motor delays, learning disorders, ADHD, autism spectrum disorder, anxiety, and executive function problems. Although SCAs have been historically underdiagnosed in young children, recent advances in noninvasive prenatal testing have resulted in an increasing nationwide cohort of infants with confirmed diagnoses. Consequently, early childhood support systems must prepare for an influx of children with known risks for associated developmental delays and potential school problems. This national survey aimed to update our understanding of current early childhood intervention services for young children with SCA in the United States and to describe parent perspectives and priorities. Descriptive statistics, chi-square tests, and logistic regression models controlling for parent education revealed a majority of respondents reported receiving public early childhood intervention services with speech therapy as the most common service. There were significant differences in early childhood intervention services by timing of diagnosis (prenatal vs. postnatal), number of sex chromosomes (trisomy vs. tetra/pentasomy), and geographic location. Parents described interventions as desirable and effective yet also difficult to obtain due to issues with the SCA phenotype, lack of provider knowledge, and challenges navigating the intervention systems. Results support the need for enhanced provider training in SCAs, policy change for early childhood intervention qualification criteria for SCA conditions, and collaboration between medical and early childhood settings., (© 2020 Wiley Periodicals, Inc.)

Sex chromosome trisomies (SCT), including Klinefelter syndrome/XXY, Trisomy X, and XYY syndrome, occur in 1 of every 500 births. The past decades of research have resulted in a broadening of known associated medical comorbidities as well as advances in psychological research. This review summarizes what is known about early neurodevelopmental, behavioral, and medical manifestations in young children with SCT. We focus on recent research and unanswered questions related to the risk for neurodevelopmental disorders that commonly present in the first years of life and discuss the medical and endocrine manifestations of SCT at this young age. The increasing rate of prenatal SCT diagnoses provides the opportunity to address gaps in the existing literature in a new birth cohort, leading to development of the eXtraordinarY Babies Study. This study aims to better describe and compare the natural history of SCT conditions, identify predictors of positive and negative outcomes in SCT, evaluate developmental and autism screening measures commonly used in primary care practices for the SCT population, and build a rich data set linked to a bank of biological samples for future study. Results from this study and ongoing international research efforts will inform evidence-based care and improve health and neurodevelopmental outcomes., (© 2020 Wiley Periodicals, Inc.)

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 < 40). Group comparisons were conducted. Multiple linear regression examined which factors contributed to ASC score. Twenty-eight females (55.6%) had adaptive skills deficits with functional communication being the most commonly affected adaptive domain. The group with ASC in the average range had higher verbal IQ (VIQ) and lower rates of numerous behavioral concerns. Internalizing behavior composite, DSM-IV inattentive symptoms score, and VIQ were significant predictors of ASC. Prenatally diagnosed females comprised over 70% of those with average adaptive skills. In this study, internalizing behaviors, inattentive ADHD symptoms, and VIQ were associated with poorer adaptive functioning. Early interventions targeting internalizing behaviors, attention/executive functioning, and communication skills may improve adaptive skills and deserve further study., (© 2020 Wiley Periodicals LLC.)

Individuals with Turner syndrome (TS) are at risk for a constellation of neurocognitive and psychosocial differences, although there is significant individual variability in these features. TS is associated with an increased risk for difficulties with visual-spatial reasoning, visual-spatial memory, attention, executive functioning, motor, and math skills. Additionally, increased rates of social difficulties, anxiety, and depression are observed. There can be significant interplay between all of these factors contributing to the behavioral phenotype. Neuropsychological features and previous research are reviewed. Clinical considerations and recommendations for evaluation and treatment of psychological and behavioral difficulties are provided, including consideration of medical features in TS, as well as therapies, educational supports, and medication treatment. Future research is needed to evaluate effectiveness of different treatments for neuropsychological and psychosocial features of TS, including modification and validation of existing evidence-based treatments and new approaches to care., (© 2019 Wiley Periodicals, Inc.)

The objectives of the study were to assess the attitudes and experiences of clinicians involved in a consortium of clinics serving people with fragile X-associated disorders to gauge satisfaction with the consortium and its efforts to improve quality of life for patients and the community. An internet survey was sent to 26 fragile X (FX) clinic directors participating in the Fragile X Clinical and Research Consortium (FXCRC). Respondents were asked to complete 19 questions on consortium performance and outcomes relevant for their own clinic. The response rate was 84% (22/26), with two surveys providing incomplete data. Assistance with clinic establishment, opportunities for research collaborations, and access to colleagues and information were highly valued. Approximately 76% of clinicians reported improvements in patient care and 60% reported an increase in patient services. There was a 57% increase in participation in a FX-related clinical trial among clinics since joining the FXCRC (24% vs. 81%). Overall, respondents reported primarily positive experiences from participation in the FXCRC. Common suggestions for improvement included additional financial support and increased utilization of collected patient data for research purposes. Additionally, a Clinic Services Checklist was administered annually to examine changes in services offered over time. There were several important changes regarding the provision of services by clinics, often with multiple clinics changing with respect to a service. In conclusion, the FXCRC has led to the establishment and sustainment of fragile X clinics in the U.S., fostered cooperation among fragile X clinicians, and provided clinics with a platform to share recommendations and best practices to maximize quality of life for their patients and the overall fragile X community. The results from the survey and checklist also provide suggestions to strengthen the FXCRC and enhance future collaborations among FXCRC members. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

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., (© 2016 Wiley Periodicals, Inc.)

47,XXY/Klinefelter syndrome is the most common sex chromosomal aneuploidy, yet 64% of males with this condition go undiagnosed. 48,XXYY is less common and there is less known about the diagnosis. The objective of this study is to describe the diagnosis experiences of parents of males with 47,XXY and 48,XXYY. Parents of 89 males with 47,XXY and 76 males with 48,XXYY completed a survey that gathered data about their experiences leading to a diagnosis, including the current age of the child, age at diagnosis, reasons for initial concern, and the specialists providing the diagnosis. In the 47,XXY cohort diagnosed postnatally, 59% presented with developmental delay, with a mean age at first parental concern of 5.2 years and mean age of diagnosis at 10.0 years. The remaining 41% presented with endocrinologic issues with a mean age at first concern of 19.1 years and mean age of diagnosis at 21.1 years. In the 48,XXYY group, 93% presented with developmental delay, with mean age at first parental concern of 2.4 years and mean age of diagnosis at 7.6 years. Hence, the average time from initial parental concern to diagnosis of 47,XXY or 48,XXYY ranges from 2 to 5 years, with those presenting with developmental issues having a longer lag to diagnosis compared to those presenting with endocrinologic issues. Increased awareness of the developmental, psychological, and medical features of 47,XXY and 48,XXYY is important to facilitate timely diagnosis and initiation of appropriate screenings and treatments that are important for optimal outcomes., (Copyright © 2013 Wiley Periodicals, Inc.)

Unlabelled: Sex chromosome tetrasomy and pentasomy conditions occur in 1:18,000-1:100,000 male births. While often compared with 47,XXY/Klinefelter syndrome because of shared features including tall stature and hypergonadotropic hypogonadism, 48,XXYY, 48,XXXY and 49,XXXXY syndromes are associated with additional physical findings, congenital malformations, medical problems and psychological features. While the spectrum of cognitive abilities extends much higher than originally described, developmental delays, cognitive impairments and behavioural disorders are common and require strong treatment plans. Future research should focus on genotype-phenotype relationships and the development of evidence-based treatments., Conclusion: The more complex physical, medical and psychological phenotypes of 48,XXYY, 48,XXXY and 49,XXXXY syndromes make distinction from 47,XXY important; however, all of these conditions share features of hypergonadotropic hypogonadism and the need for increased awareness, biomedical research and the development of evidence-based treatments., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Tall stature and eunuchoid body proportions characterize patients with 47,XXY Klinefelter syndrome, whereas patients with 45,X Turner syndrome are characterized by impaired growth. Growth is relatively well characterized in these two syndromes, while few studies describe the growth of patients with higher grade sex chromosome aneuploidies. It has been proposed that tall stature in sex chromosome aneuploidy is related to an overexpression of SHOX, although the copy number of SHOX has not been evaluated in previous studies. Our aims were therefore: (1) to assess stature in 305 patients with sex chromosome aneuploidy and (2) to determine the number of SHOX copies in a subgroup of these patients (n = 255) these patients and 74 healthy controls. Median height standard deviation scores in 46,XX males (n = 6) were -1.2 (-2.8 to 0.3), +0.9 (-2.2 to +4.6) in 47,XXY (n = 129), +1.3 (-1.8 to +4.9) in 47,XYY (n = 44), +1.1 (-1.9 to +3.4) in 48,XXYY (n = 45), +1.8 (-2.0 to +3.2) in 48,XXXY (n = 9), and -1.8 (-4.2 to -0.1) in 49,XXXXY (n = 10). Median height standard deviation scores in patients with 45,X (n = 6) were -2.6 (-4.1 to -1.6), +0.7 (-0.9 to +3.2) in 47,XXX (n = 40), -0.6 (-1.9 to +2.1) in 48,XXXX (n = 13), and -1.0 (-3.5 to -0.8) in 49,XXXXX (n = 3). Height increased with an increasing number of extra X or Y chromosomes, except in males with five, and in females with four or five sex chromosomes, consistent with a nonlinear effect on height., (Copyright 2010 Wiley-Liss, Inc.)

Klinefelter syndrome (KS) or 47,XXY occurs in approximately 1 in 650 males. Individuals with KS often present with physical characteristics including tall stature, hypogonadism, and fertility problems. In addition to medical findings, the presence of the extra X chromosome can lead to characteristic cognitive and language deficits of varying severity. While a small, but significant downward shift in mean overall IQ has been reported, the general cognitive abilities of patients with KS are not typically in the intellectual disability range. Most studies support that males with KS have an increased risk of language disorders and reading disabilities. Results of other studies investigating the relationship between verbal and nonverbal/spatial cognitive abilities have been mixed, with differing results based on the age and ascertainment method of the cohort studied. Executive function deficits have been identified in children and adults with KS, however, the research in this area is limited and further investigation of the neuropsychological profile is needed. In this article, we review the strengths and weaknesses of previous cognitive and neuropsychological studies in males with KS in childhood and adulthood, provide historical perspective of these studies, and review what is known about how hormonal and genetic factors influence cognitive features in 47,XXY/KS.

This study examined whether secondary medical diagnoses that affect CNS function (i.e., seizures, malformations, or genetic disorders), are more likely to occur in individuals with fragile X syndrome (FXS) and autism spectrum disorder (FXS + ASD) or FXS alone. Ninety males (3-25 years) with FXS or FXS + ASD were evaluated for secondary medical diagnoses by medical history and examination. A significant difference in the incidence of medical problems was found between patients with FXS + ASD (38.6%) and FXS alone (18.2%, P < 0.05). Medical problems that affect the CNS are more likely to occur in those with FXS + ASD and it is probable that additional brain dysfunction associated with these medical problems enhance the risk of autism in those with FXS., (Copyright 2008 Wiley-Liss, Inc.)

XXYY syndrome occurs in approximately 1:18,000-1:40,000 males. Although the physical phenotype is similar to 47,XXY (tall stature, hypergonadotropic hypogonadism, and infertility), XXYY is associated with additional medical problems and more significant neurodevelopmental and psychological features. We report on the results of a cross-sectional, multi-center study of 95 males age 1-55 with XXYY syndrome (mean age 14.9 years), describing diagnosis, physical features, medical problems, medications, and psychological features stratified by age groups. The mean age of diagnosis was 7.7 years. Developmental delays and behavioral problems were the most common primary indication for genetic testing (68.4%). Physical and facial features varied with age, although hypertelorism, clinodactyly, pes planus, and dental problems were common across all age groups. Tall stature was present in adolescents and adults, with a mean adult stature of 192.4 cm (SD 7.5; n = 22). Common medical problems included allergies and asthma (>50%), congenital heart defects (19.4%), radioulnar synostosis (17.2%), inguinal hernia and/or cryptorchidism (16.1%), and seizures (15%). Medical features in adulthood included hypogonadism (100%), DVT (18.2%), intention tremor (71%) and type II diabetes (18.2%). Brain MRI (n = 35) showed white matter abnormalities in 45.7% of patients and enlarged ventricles in 22.8%. Neurodevelopmental and psychological difficulties were a significant component of the behavioral phenotype, with developmental delays and learning disabilities universal but variable in severity. Twenty-six percent had full-scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores <70. Rates of neurodevelopmental disorders, including ADHD (72.2%), autism spectrum disorders (28.3%), mood disorders (46.8%), and tic disorders (18.9%), were elevated with 55.9% on psychopharmacologic medication overall. Recommendations for evaluation and treatment are summarized., (2008 Wiley-Liss, Inc.)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is generally considered to be uncommon in older female carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene; however, neither prevalence, nor the nature of the clinical phenotype, has been well characterized in female carriers. In this study, we evaluated 146 female carriers (mean, 42.3 years; range, 20-75 years) with and without core features of FXTAS (tremor; gait ataxia), and 69 age-matched controls (mean, 45.8 years; range, 21-78 years). Compared with controls, carriers with definite or probable FXTAS had greater medical co-morbidity, with increased prevalence of thyroid disease (P = 0.0096), hypertension (P = 0.0020), seizures (P = 0.0077), peripheral neuropathy (P = 0.0040), and fibromyalgia (P = 0.0097), in addition to the typical symptoms of FXTAS-tremor (P < 0.0001) and ataxia (P < 0.0001). The non-FXTAS premutation group had more complaints of chronic muscle pain (P = 0.0097), persistent paraesthesias in extremities (P < 0.0001), and history of tremor (P < 0.0123) than controls. The spectrum of clinical involvement in female carriers with FXTAS is quite broad, encompassing a number of medical co-morbidities as well as the core movement disorder. The remarkable degree of thyroid dysfunction (17% in the non-FXTAS group and 50% in the FXTAS group) warrants consideration of thyroid function studies in all female premutation carriers, particularly those with core features of FXTAS., (Copyright 2008 Wiley-Liss, Inc.)

Sex chromosomal aneuploidy is the most common disorder of sex chromosomes in humans, with an incidence of 1 in 400 newborns. The addition of more than one extra X and/or Y chromosome to a normal male karyotype is less frequent and has its own distinctive physical and behavioral profile. This study examines the behavioral similarities and differences in individuals with 48,XXYY compared to 48,XXXY and 49,XXXXY. The participants include 11 males with 48,XXYY and 13 males with 48,XXXY and 49,XXXXY. Using the Vineland Adaptive Behavior, the Achenbach Child Behavior Checklist, and the Reiss Personality Profiles, parents are asked to characterize the behavior and personality of their boys with sex chromosome tetrasomy and pentasomy. Males with 48,XXYY have higher overall adaptive scales in daily living skills, socialization, and communication compared to males with 48,XXXY and 49,XXXXY. Both groups are at risk for maladaptive behavior, although 48,XXYY males are at a higher risk for internalizing and externalizing symptoms. 48,XXXY and 49,XXXXY function at a lower cognitive level and their behavior is often immature for their chronological age. Both groups display interests in helping others, but have a low tolerance for being rejected or teased. Specific recommendations and interventional strategies are provided for individuals with 48,XXYY, 48,XXXY, and 49,XXXXY., (Copyright (c) 2007 Wiley-Liss, Inc.)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurological condition occurring in fragile X premutation carriers, predominantly males, and resulting in CNS dysfunction including tremor, ataxia, Parkinsonism, and cognitive decline. Neuropathic signs have also been described. The objective of this study was to compare neuropathic signs in fragile X premutation carriers versus controls and determine the relationship of these signs to CGG repeat length and tremor/ataxia. A neuropathy scale was utilized to compare distal tendon reflexes and vibration sense in subjects from a large cohort of carriers and controls undergoing neurological exam and structured videotaping sessions for movement disorder rating. The male carrier group displayed more impairment on total neuropathy, vibration and reflex scores than the corresponding control group, while female carriers were not significantly different from controls. In males, after correction for age effects, there was a correlation between CGG repeat length and both total neuropathy and reflex impairments. Age-adjusted partial correlation analyses showed an association between neuropathy scores and severity of ataxia but not tremor in carrier males and females. These data suggest that neuropathic signs are associated with the fragile X premutation, presumably occurring through the same mechanism proposed for CNS disease, namely, toxicity from expanded-CGG-repeat FMR1 mRNA., ((c) 2006 Wiley-Liss, Inc.)

Background: Although Helicobacter pylori DNA sequences have been detected in cholecystic bile and tissue of patients with gallstones, controversial results are reported from different geographic areas., Aim: To detect H. pylori in cholecystic bile and tissue of patients with gallstones from a previously uninvestigated geographic area, southern Italy. Detection included both the bacterial DNA and the specific antigen (H. pylori stool antigen) identified in the stools of infected patients for diagnostic purposes., Patients and Methods: The study enclosed 33 consecutive patients undergoing laparoscopic cholecystectomy for gallstones. DNA sequences of H. pylori were detected by polymerase chain reaction in both cholecystic bile and tissue homogenate. Moreover, we assayed H.pylori stool antigen on gall-bladder cytosolic and biliary proteins after their extraction. Bacterial presence in the stomach was assessed by urea breath test in all patients and Deltadelta13CPDB value assumed as marker of intragastric load. Fisher's exact probability and Student's t-tests were used for statistical analysis., Results: DNA sequences of H. pylori in bile were found in 51.5% and significantly correlated with its presence in cholecystic tissue homogenate (P<0.005), H. pylori stool antigen in gall-bladder (P=0.0013) and bile (P=0.04) proteins, gastric infection (P<0.01) and intragastric bacterial load (P<0.001). No correlation was found, however, with sex and age of the patients., Conclusions: Our prevalence value of bacterial DNA in bile and gall-bladder of patients with gallstones agreed with that of the only other Italian study. The simultaneous presence of both bacterial DNA and proteic antigen suggests that the same prototype of bacterium could be located at both intestinal and cholecystic level and, therefore, the intestine represents the source of biliary contagion.

The clinical significance of an interstitial duplication of (15)(q11-q13) remains unclear and controversial. The reported phenotypes vary widely and appear to be influenced by the parent of origin of the duplication. Aside from cases of dup(15) reported with autism, the behavioral phenotype of individuals with dup(15) has not been described. We present three families, two with intrachromosomal duplication (15)(q11-q13) ascertained because of developmental delay in a relative. Two families show clear evidence of multigenerational maternal inheritance. The individuals discussed in this paper have minor anomalies and developmental delays. In addition, we describe a behavioral phenotype which often includes attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder. Responses to medications used to manage these behaviors are also described, including a positive response to methylphenidate and a poor response to fluoxetine. The duplication in each presenting individual, and available family members, was investigated utilizing cytogenetic and molecular techniques including high resolution cytogenetics, fluorescence in situ hybridization (FISH), DNA methylation studies, and quantitative fluorescence PCR. High resolution cytogenetic techniques alone missed some cases, demonstrating the need to confirm results with other methods., (Copyright 2003 Wiley-Liss, Inc.)