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Willi Syndrome (willi + syndrome)
Selected AbstractsPrader,Willi Syndrome: Development and ManifestationsJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 7 2005Colin Hemmings [source] Identification of CpG methylation of the SNRPN gene by methylation-specific multiplex PCRELECTROPHORESIS, Issue 2 2009Chia-Cheng Hung Abstract In this article, we show that methylation-specific multiplex PCR (MS-multiplex PCR) is a sensitive and specific single assay for detecting CpG methylation status as well as copy number aberrations. We used MS-multiplex PCR to simultaneously amplify three sequences: the 3, ends of the SNRPN gene (for unmethylated sequences), the KRITI gene (as internal control), and the promoter of the SNRPN gene containing CpG islands (for methylated sequences) after digestion with a methylation-sensitive restriction enzyme (HhaI). We established this duplex assay for the analysis of 38 individuals with Prader,Willi syndrome, 2 individuals with Angelman syndrome, and 28 unaffected individuals. By comparing the copy number of the three regions, the methylation status and the copy number changes can be easily distinguished by MS-multiplex PCR without the need of bisulfite treatment of the DNA. The data showed that MS-multiplex PCR allows for the estimation of the methylation level by comparing the copy number aberrations of unknown samples to the standards with a known methylated status. The in-house-designed MS-multiplex PCR protocol is a relatively simple, cost-effective, and highly reproducible approach as a significant strategy in clinical applications for epigenetics in a routine laboratory. [source] Cognitive profile in a large french cohort of adults with Prader,Willi syndrome: differences between genotypesJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 3 2010P. Copet Abstract Background Prader,Willi syndrome (PWS) is a rare genetic disorder characterised by developmental abnormalities leading to somatic and psychological symptoms. These include dysmorphic features, impaired growth and sexual maturation, hyperphagia, intellectual delay, learning disabilities and maladaptive behaviours. PWS is caused by a lack of expression of maternally imprinted genes situated in the 15q11-13 chromosome region. The origin is a ,de novo' deletion in the paternal chromosome in 70% of the cases and a maternal uniparental disomy in 25%. The two main genotypes show differences, notably regarding cognitive and behavioural features, but the mechanisms are not clear. This study assessed cognitive impairment in a cohort of adults with genetically confirmed PWS, analysed their profiles of cognitive strengths and weaknesses, and compared the profiles in terms of genotype. Methods Ninety-nine male and female adults participated, all inpatients on a specialised unit for the multidisciplinary care of PWS. The Wechsler Adult Intelligence Scale (WAIS-III) was administered to all patients in identical conditions by the same psychologist. Eighty-five patients were able to cope with the test situation. Their scores were analysed with non-parametric statistical tools. The correlations with sex, age and body mass index were explored. Two genotype groups were compared: deletion (n = 57) and non-deletion (n = 27). Results The distribution of intelligence quotients in the total cohort was non-normal, with the following values (medians): Full Scale Intelligence Quotient (FSIQ): 52.0 (Q1:46.0; Q3:60.0), Verbal Intellectual Quotient (VIQ): 53.0 (Q1:48; Q3:62) and Performance Intellectual Quotient (PIQ): 52.5 (Q1:48; Q3:61). No correlation was found with sex, age or body mass index. Comparison between groups showed no significant difference in FSIQ or VIQ. PIQ scores were significantly better in the deletion group. The total cohort and the deletion group showed the VIQ = PIQ profile, whereas VIQ > PIQ was observed in the non-deletion group. The subtest scores in the two groups showed significant differences, with the deletion group scoring better in three subtests: object assembly, picture arrangement and digit symbol coding. Some relative strengths and weaknesses concerned the total cohort, but others concerned only one genotype. Discussion We documented a global impairment in the intellectual abilities of a large sample of French PWS patients. The scores were slightly lower than those reported in most other studies. Our data confirmed the previously published differences in the cognitive profiles of the two main PWS genotypes and offer new evidence to support this hypothesis. These results could guide future neuropsychological studies to determine the cognitive processing in PWS. This knowledge is essential to improve our understanding of gene-brain-behaviour relationships and to open new perspectives on therapeutic and educational programmes. [source] Relationship between the IQ of people with Prader,Willi syndrome and that of their siblings: evidence for imprinted gene effectsJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 5 2009J. Whittington Abstract Background Genetic disorders occasionally provide the means to uncover potential mechanisms linking gene expression and physical or cognitive characteristics or behaviour. Prader,Willi syndrome (PWS) is one such genetic disorder in which differences between the two main genetic subtypes have been documented (e.g. higher verbal IQ in one vs. higher performance IQ in the other; slower than normal reaction time in one vs. normal in the other). In a population study of PWS, the IQ distribution of people with PWS was approximately normal. This raises the question of whether this distribution arose from a systematic effect of PWS on IQ (hypothesis 1) or whether it was the fortuitous result of random effects (hypothesis 2). Method The correlation between PWS and sibling IQ was determined in order to discriminate between the two hypotheses. In the first case we would expect the correlation to be similar to that found in the general population (0.5); in the second case it would be zero. Results It was found that the overall PWS,sibling IQ correlation was 0.3 but that the two main genetic subtypes of PWS differed in their familial IQ relationships. As expected, the IQs of normal siblings correlated 0.5, and this was also the case with one genetic subtype of PWS (uniparental disomy) and their siblings, while the other subtype IQ correlated ,0.07 with sibling IQ. Conclusions This is a potentially powerful result that gives another clue to the role of genes on chromosome 15 in the determination of IQ. It is another systematic difference between the genetic subtypes of PWS, which needs an explanation in terms of the very small genetic differences between them. [source] A neuropsychological assessment of frontal cognitive functions in Prader,Willi syndromeJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 5 2007J. Jauregi Abstract Background Prader,Willi syndrome (PWS) is associated with a characteristic behavioural phenotype whose main features are, alongside compulsive hyperphagia, deficits in social behaviour: social withdrawal, temper tantrums, perseverative speech and behaviour, mental rigidity, stereotyped behaviour, impulsiveness, etc. Similar symptoms may also be found in autistic spectrum disorders and lesional pathologies of the frontal lobe. In both cases, such symptoms have been related to dysfunctions in frontal cognitive processes such as attention, working memory and executive functions. This study uses standardized neuropsychological instruments to analyse the degree to which these processes are affected in PWS. Methods The sample comprised 16 individuals with a genetically confirmed PWS diagnosis. Subjects' IQ (Wechsler Adult Intelligence Scale), academic level, laterality and body mass index (BMI) were calculated. Attention, memory and executive functions were analysed using standard, widely employed neuropsychological tests. We compared the results of the sample group with the general population. Correlation analyses were carried out with IQ, academic level and BMI. Results In all the neuropsychological measures focusing on attention, executive functions and visuoperceptual organization, the study sample scored significantly lower than the normative reference population. The scores of the tests used for measuring immediate memory were also significantly lower when trials required sequential processing, although not when they required simultaneous processing. In the memorization of a list of words, subjects showed an initial deficit which disappeared with repetition, enabling them to obtain scores similar to the reference population. No significant correlations were found with BMI, and a higher IQ or academic level did not improve scores in the majority of tests. Conclusions The study shows a deficit in elementary frontal cognitive processes in PWS patients. This deficit may be involved in the social behaviour disorders that characterize such patients, as described in other development or frontal syndrome pathologies. However, we cannot affirm that the deficits found are specific to PWS; they could also occur in other causes of intellectual disability. Although in the study sample IQ did not correlate with frontal deficits, further research is needed to establish whether the neuropsychological alterations described form part of a cognitive phenotype for PWS. We believe that our understanding of the social behaviours typical of PWS may be improved by taking into consideration the cognitive functioning models of the prefrontal lobe, particularly those applied to pervasive developmental disorders. [source] An investigation into food preferences and the neural basis of food-related incentive motivation in Prader,Willi syndromeJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 9 2006E. C. Hinton Abstract Background Research into the excessive eating behaviour associated with Prader,Willi syndrome (PWS) to date has focused on homeostatic and behavioural investigations. The aim of this study was to examine the role of the reward system in such eating behaviour, in terms of both the pattern of food preferences and the neural substrates of incentive in the amygdala and orbitofrontal cortex (OFC). Method Participants with PWS (n = 18) were given a food preference interview to examine food preferences and to inform the food-related incentive task to be conducted during the neuroimaging. Thirteen individuals with PWS took part in the positron emission tomography (PET) study, the design of which was based on a previous study of non-obese, non-PWS controls. For the task, participants were asked to consider photographs of food and to choose the food they would most like to eat in two conditions, one of high and one of low incentive foods, tailored to each participant's preferences. For comparison of the food preference data, 12 non-PWS individuals were given one part of the interview. Results Individuals with PWS expressed relative liking of different foods and showed preferences that were consistent over time, particularly for sweet foods. The participants with PWS did give the foods in the high incentive condition a significantly higher incentive value than the foods in the low incentive condition. However, activation of the amygdala and medial OFC was not associated with the prospect of highly valued foods as predicted in those with PWS. Conclusions It would appear that incentive motivation alone plays a less powerful role in individuals with PWS than in those without the syndrome. This is likely to be due to the overriding intrinsic drive to eat because of a lack of satiety in those with PWS, and the impact of this on activity in the incentive processing regions of the brain. Activity in such reward areas may not then function to guide behaviour selectively towards the consumption of high preference foods. [source] Repetitive and ritualistic behaviour in children with Prader,Willi syndrome and children with autismJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 2 2006N. Greaves Abstract Background Recent research has shown that the range of repetitive behaviour seen in individuals with Prader,Willi syndrome (PWS) extends beyond food-related behaviour. Methods The presence and intensity of repetitive, rigid and routinized behaviour in children with PWS was compared with that seen in children with another neurodevelopmental condition in which repetitive behaviour is common: children with autism. Parents completed the Childhood Routines Inventory (CRI). Results Contrary to our predictions, controlling for developmental level, children with PWS and children with autism showed similar levels of repetitive and ritualistic behaviour overall and on the two CRI factors measuring ,just right' and ,repetitive' behaviour. Indeed, the majority of the sample of parents of children with PWS endorsed most items on the CRI. However there was some specificity at the level of individual items with parents of children with PWS more frequently endorsing an item on ,collecting and storing objects' and parents of children with autism more frequently endorsing ,lining up objects', ,has a strong preference for certain foods' and ,seems aware of detail at home'. Conclusions These findings confirm the range of repetitive behaviours that form part of the behavioural phenotype of PWS, including insistence on sameness and ,just right' behaviours, and uncover a surprising overlap with those seen in children with autism. Clinical management for children with PWS should include advice and education regarding management of repetitive and rigid behaviour. Future research should investigate whether the repetitive behaviours that form part of the behavioural phenotype of both PWS and autism are associated with a common neuropsychological, neurotransmitter or genetic origin. [source] A measure of food seeking in individuals with Prader,Willi syndromeJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 1 2006J. Young Abstract Background Individuals with Prader,Willi syndrome (PWS), a chromosome 15 genetic disorder, often have a significant preoccupation with food and problem behaviour related to food seeking is often prevalent. Methods In the present study, we compared how individuals with PWS responded on a survey regarding the acceptability of food in various locations that varied according to degree of appropriateness for human consumption (e.g. food on a plate, food in a garbage can). For a subgroup of participants, we observed how they actually responded when placed in a room with food items placed in the same locations depicted in the survey. In the first part of the study, three groups (25 typically developing individuals, 7 individuals with intellectual disability (ID), and 19 individuals with PWS) responded to a visual survey to determine the degree of acceptability of food items in various locations (e.g. on a table near a hairbrush, on the floor behind a toy box, in a trash can). In the second part of the study, these food items (popcorn, jelly beans) were placed in the 12 locations described above. Nine individuals diagnosed with PWS (deletion type) and three individuals with ID were given some break time in the room for 15 min. The amount of food consumed, the time spent food seeking, and time spent interacting with materials were measured. Results Results of the survey indicated that the PWS group differed significantly with regard to how they responded on the survey from the typically developing group, but did not differ significantly from the ID group. Results of the food seeking observations indicated that only three individuals with PWS ate a significant number of items. The three individuals did not differ from the rest of the group according to IQ or compulsivity score; however, they had significantly lower body mass index (BMI) scores and were younger than the other participants. Conclusions The findings from the survey indicate that individuals with PWS are able to discriminate the appropriateness of eating items in more or less contaminated areas; however, the amount of time spent seeking food and the amount of food covertly consumed appeared to depend more directly on age and BMI. [source] Rituals and compulsivity in Prader,Willi syndrome: profile and stabilityJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 6 2003M. Wigren Abstract Background Prader,Willi syndrome (PWS) is characterized by an increased risk for obsessive,compulsive disorder. This study investigated the nature of compulsive-like behaviours in the PWS. Method Parents of 50 individuals with PWS (aged 5,18 years) and 50 typically developing 4-year-old children completed the Childhood Routines Inventory. This instrument measures compulsive-like behaviours in normative childhood. Results Many childhood compulsive behaviours are prevalent among older children and adolescents with PWS. Group differences were observed in that the PWS group, independent of age, gender and cognitive dysfunctions, exhibited more intense compulsive behaviours related to insistence on sameness in many daily activities and social contexts. Findings also revealed an age-independent low-prevalent pattern of PWS compulsivity, probably related to other features in the PWS symptomatology. Conclusions Compulsions of childhood do not subside with age in adolescents with PWS. The findings indicate that the differentiation between delayed childhood rituals and pathological manifestations of compulsive features is complex in PWS populations. [source] Autonomy and intellectual disability: the case of prevention of obesity in Prader,Willi syndromeJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 7 2002R. H. van Hooren Abstract Background The policy concerning care for people with intellectual disability (ID) has developed from segregation via normalization towards integration and autonomy. Today, people with ID are seen as citizens who need to be supported to achieve a normal role in society. The aim of care is to optimize quality of life and promote self-determination. The promotion of autonomy for people with ID is not easy and gives rise to ethical dilemmas. Caregivers are regularly confronted with situations in which there is a conflict between providing good care and respecting the client's autonomy. This becomes evident in the case of prevention of obesity in people with Prader,Willi syndrome (PWS). Method As part of a study about the ethical aspects of the prevention of obesity, in-depth qualitative interviews were conducted with the parents and professional caregivers of people with PWS. Results In analysing interviews with parents and formal caregivers, the present authors found that the dichotomy between respecting autonomy and securing freedom of choice on the one hand, and paternalism on the other, is too crude to do justice to the process of care. The stories indicated that caregivers see other options and act in other ways than to intervene without taking into account the wishes of the individual with PWS. The present authors elaborated these options, taking models of the physician,patient relationship as a heuristic starting point. They extended the logic of these models by focusing on the character of the process of interaction between caregiver and care receiver, and on the emotional aspects of the interactions. Conclusion This approach results in more attention to processes of interpretation, deliberation and joint learning. [source] Intellectual characteristics of Prader,Willi syndrome: comparison of genetic subtypesJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 1 2000E. Roof Advances in genetics have led to an increased understanding of the role of the genotype on behavioural functioning. The purpose of the present study was to examine differences in intellectual functioning in individuals with Prader,Willi syndrome (PWS) with a paternal 15q11,q13 deletion versus maternal uniparental disomy (UPD) of chromosome 15. Measures of intelligence and academic achievement were administered to 38 individuals with PWS (24 with deletion and 14 with UPD). The subjects with UPD had significantly higher verbal IQ scores than those with deletion (P0.01). The magnitude of the difference in verbal IQ was 9.1 points (69.9 versus 60.8 for UPD and deletion PWS subjects, respectively). Only 17% of subjects with the 15q11,q13 deletion had a verbal IQ,70, while 50% of those with UPD had a verbal IQ,70. Performance IQ scores did not differ between the two PWS genetic subtype groups. This is the first report to document the difference between verbal and performance IQ score patterns among subjects with PWS of the deletion versus the UPD subtype. [source] Uniparental disomy and human disease: An overview,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2010Kazuki Yamazawa Abstract Uniparental disomy (UPD) refers to the situation in which both homologues of a chromosomal region/segment have originated from only one parent. This can involve the entire chromosome or only a small segment. As a consequence of UPD, or uniparental duplication/deficiency of part of a chromosome, there are two types of developmental risk: aberrant dosage of genes regulated by genomic imprinting and homozygosity of a recessive mutation. UPD models generated by reciprocal and Robertsonian translocation heterozygote intercrosses have been a powerful tool to investigate genomic imprinting in mice, whereas novel UPD patients such as those with cystic fibrosis and Prader,Willi syndrome, triggered the clarification of recessive diseases and genomic imprinting disorders in human. Newly developed genomic technologies as well as conventional microsatellite marker methods have been contributing to the functional and mechanistic investigation of UPD, leading to not only the acquisition of clinically valuable information, but also the further clarification of diverse genetic processes and disease pathogenesis. © 2010 Wiley-Liss, Inc. [source] Prader,Willi syndrome and Angelman syndrome,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2010Karin Buiting Abstract Prader,Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct neurogenetic disorders in which imprinted genes on the proximal long arm of chromosome 15 are affected. Although the SNORD116 gene cluster has become a prime candidate for PWS, it cannot be excluded that other paternally expressed genes in the chromosomal region 15q11q13 contribute to the full phenotype. AS is caused by a deficiency of the UBE3A gene, which in the brain is expressed from the maternal allele only. The most frequent genetic lesions in both disorders are a de novo deletion of the chromosomal region 15q11q13, uniparental disomy 15, an imprinting defect or, in the case of AS, a mutation of the UBE3A gene. Microdeletions in a small number of patients with PWS and AS have led to the identification of the chromosome 15 imprinting center (IC). The IC consists of two critical elements, which act in cis to regulate imprinting in the whole chromosome 15q11q13 imprinted domain. © 2010 Wiley-Liss, Inc. [source] Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for microdeletion syndromes and subtelomere imbalancesPRENATAL DIAGNOSIS, Issue 10 2010S. Kjaergaard Abstract Objective The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader,Willi/Angelman, Miller,Dieker, Smith,Magenis, 1p-, Williams), the reciprocal microduplication syndromes and imbalance at the subtelomere regions of chromosomes in a routine prenatal setting. Method A total of 530 prenatal samples were analysed by commercial MLPA kits (SALSA P064, P036 and P069) in addition to rapid aneuploidy testing and G-band karyotyping. Results Among the prenatal samples with a normal metaphase karyotype, nine submicroscopic imbalances were detected: seven 22q11 deletions (Velocardiofacial/DiGeorge syndrome), one 15q11deletion (Prader,Willi syndrome) and one terminal deletion of the short arm of chromosome 4 (Wolf,Hirschhorn syndrome). All imbalances were found in amniocentesis (AC) taken due to fetal structural malformation and/or other ultrasound scan (US) detected abnormality. The diagnostic yield was 4.1% in the subgroup with structural malformation and 1.6% in the subgroup with other US abnormality. Conclusion The data set substantiates that additional MLPA analyses for selected microdeletions and subtelomere imbalances are valuable in routine prenatal diagnostics, when a malformation(s) and/or other abnormalities are detected by US. In contrast, the additional MLPA analyses gave no diagnostic yield in case of increased nuchal translucency (NT). Copyright © 2010 John Wiley & Sons, Ltd. [source] Relationship between hypersomnia and respiratory disorder during sleep in Prader,Willi syndromePSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2000Yu Hiroe MD Abstract To assess whether hypersomnia in Prader,Willi syndrome (PWS) patients is related to the respiratory disorder during sleep (RDDS), we made a systematic evaluation regarding the relationship between the two disorders in three patients. All patients showed hypersomnia manifested as the long duration of night sleep and shortened sleep latencies of multiple sleep latency test. Although magnetic resonance imaging and laboratory studies revealed obstruction of the upper airway and mild increase of esophageal pressure during sleep, the number of other apneic episodes or awakenings was not as frequent. From the above results, we speculate that the mechanism of excessive daytime sleepiness in PWS is not caused by RDDS and quite resembles that of essential hypersomnia. [source] Adrenal function and mortality in children and adolescents with Prader,Willi syndrome attending a single centre from 1991,2009CLINICAL ENDOCRINOLOGY, Issue 5 2010Natalie A. Connell No abstract is available for this article. [source] Altered distribution of adiponectin isoforms in children with Prader,Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormonesCLINICAL ENDOCRINOLOGY, Issue 6 2007Andrea M. Haqq Summary Objective, Prader,Willi syndrome (PWS) is a genetic syndrome characterized by relative hypoinsulinaemia and normal or increased insulin sensitivity despite profound obesity. We hypothesized that this increased insulin sensitivity is mediated by increased levels of total and high molecular weight adiponectin and associated with changes in levels of satiety hormones. Design, patients and measurements, We measured total adiponectin and its isoforms [high molecular weight (HMW), middle molecular weight (MMW) and low molecular weight (LMW) adiponectin] and satiety hormones in 14 children with PWS [median age 11·35 years, body mass index (BMI) Z- score 2·15] and 14 BMI-matched controls (median age 11·97 years, BMI Z- score 2·34). Results, Despite comparable BMI Z- scores and leptin levels, the PWS children exhibited lower fasting insulin and HOMA-IR (homeostasis model assessment of insulin resistance) scores compared to obese controls. For any given BMI Z- score, the PWS children showed higher concentrations of fasting total and HMW adiponectin and higher HMW/total adiponectin ratios. The HMW/total adioponectin ratio was preserved in children with PWS at high degrees of obesity. In PWS children, fasting plasma total adiponectin, HMW adiponectin and HMW/total adiponectin ratio correlated negatively with age (P < 0·05), HOMA-IR (P < 0·01), BMI Z- score (P < 0·05), insulin (P < 0·01) and leptin (P < 0·05). In addition to higher fasting ghrelin concentrations, the PWS children showed significantly higher fasting levels of total peptide YY (PYY) and gastric inhibitory polypeptide (GIP) compared to obese controls. Conclusions, Relative to controls of similar age and BMI Z- score, the PWS children had significantly higher levels of total and HMW adiponectin, and increased ratios of HMW/total adiponectin. These findings may explain in part the heightened insulin sensitivity of PWS children relative to BMI-matched controls. [source] Thyroid hormone levels in children with Prader,Willi syndrome before and during growth hormone treatmentCLINICAL ENDOCRINOLOGY, Issue 3 2007D. A. M. Festen Summary Background, Prader,Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, obesity and short stature. Several endocrine abnormalities have been described, including GH deficiency and hypogonadotrophic hypogonadism. Published data on thyroid hormone levels in PWS children are very limited. Objective, To evaluate thyroid function in children with PWS, before and during GH treatment. Design/patients, At baseline, serum levels of T4, free T4 (fT4), T3, reverse T3 (rT3) and TSH were assessed in 75 PWS children. After 1 year, assessments were repeated in 57 of the them. These children participated in a randomized study with two groups: group A (n = 34) treated with 1 mg GH/m2/day and group B (n = 23) as controls. Results, Median age (interquartile range, IQR) of the total group at baseline was 4·7 (2·7,7·6) years. Median (IQR) TSH level was ,0·1 SDS (,0·5 to 0·5), T4 level ,0·6 SDS (,1·7 to 0·0) and fT4 level ,0·8 SDS (,1·3 to ,0·3), the latter two being significantly lower than 0 SDS. T3 level, at 0·3 SDS (,0·3 to 0·9), was significantly higher than 0 SDS. After 1 year of GH treatment, fT4 decreased significantly from ,0·8 SDS (,1·5 to ,0·2) to ,1·4 SDS (,1·6 to ,0·7), compared to no change in untreated PWS children. However, T3 did not change, at 0·3 SDS (,0·1 to 0·8). Conclusions We found normal fT4 levels in most PWS children. During GH treatment, fT4 decreased significantly to low-normal levels. TSH levels remained normal. T3 levels were relatively high or normal, both before and during GH treatment, indicating that PWS children have increased T4 to T3 conversion. [source] Prader,Willi syndrome phenocopy due to duplication of Xq21.1,q21.31, with array CGH of the critical regionCLINICAL GENETICS, Issue 4 2008MT Gabbett We report on a 4-year-old male with an interstitial tandem duplication of Xq21.1,q21.31 who presented with clinical features of Prader,Willi syndrome (PWS). The duplication was maternally inherited. Abnormalities of the X chromosome have previously been reported in association with a PWS phenotype, but to date, specific duplications of Xq21.1,q21.31 have not. We refined the chromosomal breakpoints seen on initial G-banded karyotyping in our case with comparative genomic hybridization by microarray (array CGH). The duplication was between 11.1 and 14.4 Mb in length and overlaps with three loci to which mental retardation with PWS-like features have been previously mapped, showing the utility of array CGH in helping to identify candidate genes. We conclude that duplication of chromosomal region Xq21.1,q21.31 potentially results in a PWS-like phenotype. Reviewing the literature on similar duplications, we further conclude that distal Xq duplications can result in features typically seen in infants with PWS, while proximal duplications can result in features typically seen in older children and adults with PWS. Duplications of chromosome Xq should be considered in the differential diagnosis of PWS, especially in males. [source] | |||||||||||||