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Pediatric Endocrinology, Diabetes, and... 2022Prader-Willi syndrome (PWS) is a genetically determined disease that manifests itself in a number of abnormalities resulting, among others, from dysfunction of the... (Review)
Review
INTRODUCTION
Prader-Willi syndrome (PWS) is a genetically determined disease that manifests itself in a number of abnormalities resulting, among others, from dysfunction of the hypothalamic-pituitary system. Only integrated, multidisciplinary care gives patients the chance to significantly improve the quality of life and achieve a life expectancy that does not differ from the general population.
AIM
The aim of the study was to summarize the available literature on the management of patients suffering from PWS.
CONCLUSIONS
More and more reports based on clinical trials conducted around the world indicate the undeniable benefits of rhGH therapy in patients with PWS in childhood and after the end of growth period. They consist in improving the body composition, improving the lipid profile, increasing bone mineral density and improving the mental state and patients' quality of life.
Topics: Adult; Body Composition; Child; Human Growth Hormone; Humans; Prader-Willi Syndrome; Quality of Life; Recombinant Proteins
PubMed: 35307998
DOI: 10.5114/pedm.2022.112861 -
Pediatric Endocrinology, Diabetes, and... 2017Prader-Willi Syndrome is a genetic condition caused by an abnormality of chromosome 15, mostly resulting from a deletion.The prevalence of syndrome in Europe has been... (Review)
Review
Prader-Willi Syndrome is a genetic condition caused by an abnormality of chromosome 15, mostly resulting from a deletion.The prevalence of syndrome in Europe has been reported between 1 in 8,000 to 1 in 45,000 births. Characteristic features of the syndrome include hypotonia, short stature, psychomotor development delay, hypogonadism and progressive, life-threatening obesity. Treatment of Prader-Willi Syndrome consists of intensive rehabilitation, psychologicalcare, speech therapy and also, if patient is fulfilling appropriate criteria, growth hormone treatment. An extremely important element of therapy is also properly planned and implemented nutritional management. Adequate diet prevents the malnutrition in the first stage of life and the development of excessive weight in subsequent years. The aim of this article is to provide practical and accurate guidance on nutritional management and diet therapy for physicians and nutritionists who work with children, adolescents and adults with Prader-Willi Syndrome.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 15; Diet Therapy; Europe; Female; Humans; Infant; Male; Middle Aged; Practice Guidelines as Topic; Prader-Willi Syndrome; Prevalence; Young Adult
PubMed: 29073293
DOI: 10.18544/PEDM-23.02.0080 -
Orphanet Journal of Rare Diseases Jan 2020Prader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder of genetic origin. It manifests itself in endocrine and cognitive problems, including...
BACKGROUND
Prader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder of genetic origin. It manifests itself in endocrine and cognitive problems, including highly pronounced hyperphagia and severe obesity. In many cases, impaired acquisition of social and communication skills leads to autism spectrum features, and individuals with this syndrome are occasionally diagnosed with autism spectrum disorder (ASD) using specific scales. Given that communicational skills are largely based on vocal communication, it is important to study human voice processing in PWS. We were able to examine a large number of participants with PWS (N = 61) recruited from France's national reference center for PWS and other hospitals. We tested their voice and nonvoice recognition abilities, as well as their ability to distinguish between voices and nonvoices in a free choice task. We applied the hierarchical drift diffusion model (HDDM) with Bayesian estimation to compare decision-making in participants with PWS and controls.
RESULTS
We found that PWS participants were impaired on both voice and nonvoice processing, but displayed a compensatory ability to perceive voices. Participants with uniparental disomy had poorer voice and nonvoice perception than participants with a deletion on chromosome 15. The HDDM allowed us to demonstrate that participants with PWS need to accumulate more information in order to make a decision, are slower at decision-making, and are predisposed to voice perception, albeit to a lesser extent than controls.
CONCLUSIONS
The categorization of voices and nonvoices is generally preserved in participants with PWS, though this may not be the case for the lowest IQ.
Topics: Autism Spectrum Disorder; Bayes Theorem; Humans; Prader-Willi Syndrome; Uniparental Disomy
PubMed: 31959191
DOI: 10.1186/s13023-020-1298-8 -
Epidemiology and Health 2022Hyperphagia is a highly stressful, life-threatening feature of Prader-Willi syndrome (PWS). It is important to assess this complex behavior accurately over time. This...
OBJECTIVES
Hyperphagia is a highly stressful, life-threatening feature of Prader-Willi syndrome (PWS). It is important to assess this complex behavior accurately over time. This study aimed to develop and validate the Pediatric-Youth Hyperphagia Assessment for Prader-Willi syndrome (PYHAP) as a tool targeting children and adolescents.
METHODS
After an extensive literature review and qualitative interviews, the final version of the PYHAP with 14 questions in 3 domains (verbal [5], behavior [4], and social [5]) was developed and tested at Samsung Medical Center in Seoul, Korea from July 2018 to September 2019. Exploratory factor analysis and confirmatory factor analysis (CFA) were performed to confirm construct validity. The correlations between the PYHAP and the Korean Children's Eating Behavior Questionnaire (K-CEBQ) were calculated to evaluate convergent and discriminant validity. Criterion validity and the validity of the response categories were also tested.
RESULTS
Cronbach's alpha coefficient of the PYHAP was 0.91. The fit indices for CFA were good (comparative fit index, 0.87; standardized root mean squared residual, 0.08). The domains of the PYHAP were closely correlated with the relevant domains of the K-CEBQ. The accuracy of the PYHAP score for predicting uncontrolled hyperphagia was good (area under the curve, 0.75; 95% confidence interval, 0.65 to 0.85).
CONCLUSIONS
The PYHAP was confirmed to be a reliable and valid tool to evaluate hyperphagia in children and adolescents with PWS via caregivers' assessments. It is recommended to use the PYHAP to communicate with parents or caregivers about patients' hyperphagia or to monitor and manage extreme behaviors in children with PWS.
Topics: Adolescent; Caregivers; Child; Feeding Behavior; Humans; Hyperphagia; Prader-Willi Syndrome; Surveys and Questionnaires
PubMed: 35038830
DOI: 10.4178/epih.e2022014 -
Italian Journal of Pediatrics Jul 2022Prader-Willi syndrome (PWS) is a complex disorder caused by impaired paternally expressed genes on chromosome 15q11-q13. Variable findings have been reported about the...
BACKGROUND
Prader-Willi syndrome (PWS) is a complex disorder caused by impaired paternally expressed genes on chromosome 15q11-q13. Variable findings have been reported about the phenotypic differences among PWS genetic subtypes.
METHODS
A total of 110 PWS patients were diagnosed from 8,572 pediatric patients included from July 2013 to December 2021 by MLPA and MS-MLPA assays. Atypical deletions were defined by genomic CNV-sequencing. Maternal uniparental disomy (UPD) was subgrouped by microsatellite genotyping. Clinical data were collected for phenotype-genotype associations. Twenty-one patients received growth hormone (GH) treatment, and the anthropometric and laboratory parameters were evaluated and compared.
RESULTS
Genetically, the 110 patients with PWS included 29 type I deletion, 56 type II deletion, 6 atypical deletion, 11 heterodisomy UPD, and 8 isodisomy UPD. The UPD group had significantly higher maternal age (31.4 ± 3.4 vs 27.8 ± 3.8 years), more anxiety (64.29% vs 26.09%) and autistic traits (57.14% vs 26.09%), and less hypopigmentation (42.11% vs 68.24%) and skin picking (42.86% vs 71.01%) than the deletion group. The type I deletion group was diagnosed at earlier age (3.7 ± 3.3 vs 6.2 ± 3.2 years) and more common in speech delay (95.45% vs 63.83%) than the type II. The isodisomy UPD group showed a higher tendency of anxiety (83.33% vs 50%) than the heterodisomy. GH treatment for 1 year significantly improved the SDS of height (- 0.43 ± 0.68 vs - 1.32 ± 1.19) and IGF-I (- 0.45 ± 0.48 vs - 1.97 ± 1.12). No significant changes were found in thyroid function or glucose/lipid metabolism.
CONCLUSION
We explored the physical, psychological and behavioral phenotype-genotype associations as well as the GH treatment effect on PWS from a large cohort of Chinese pediatric patients. Our data might promote pediatricians' recognition and early diagnosis of PWS.
Topics: Humans; Body Height; Maternal Age; Phenotype; Prader-Willi Syndrome; Uniparental Disomy; Female; Adult; Child
PubMed: 35870983
DOI: 10.1186/s13052-022-01319-1 -
Frontiers in Endocrinology 2022The generalized dysfunction of the hypothalamic-pituitary axis in patients with Prader-Willi syndrome (PWS) is the most likely cause of hypogonadism, inadequate growth... (Review)
Review
The generalized dysfunction of the hypothalamic-pituitary axis in patients with Prader-Willi syndrome (PWS) is the most likely cause of hypogonadism, inadequate growth hormone secretion, excessive appetite and associated obesity, impaired body temperature regulation, and hypothyroidism. The syndrome is also related to an increased risk of central adrenal insufficiency, although its prevalence remains unknown. The results of the studies in which different methods of pharmacological stimulation were used do not provide conclusive outcomes. As a result, there are no clear guidelines with regard to diagnosis, prevention, or long-term care when adrenal insufficiency is suspected in patients with PWS. Currently, most patients with PWS are treated with recombinant human growth hormone (rhGH). It has been confirmed that rhGH therapy has a positive effect on growth, body composition, body mass index (BMI), and potentially on psychomotor development in children with PWS. Additionally, rhGH may reduce the conversion of cortisone to cortisol through inhibition of 11β-hydroxysteroid dehydrogenase type 1. However, its influence on basal adrenal function and adrenal stress response remains unexplained in children with PWS. This paper reviews the literature related to the hypothalamic-pituitary-adrenal axis dysfunction in the PWS patient population with a focus on children.
Topics: Child; Humans; Prader-Willi Syndrome; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Hydrocortisone; Human Growth Hormone; Adrenal Insufficiency
PubMed: 36465638
DOI: 10.3389/fendo.2022.1021704 -
Phylogenetic and Molecular Analyses Identify SNORD116 Targets Involved in the Prader-Willi Syndrome.Molecular Biology and Evolution Jan 2022The eutherian-specific SNORD116 family of repeated box C/D snoRNA genes is suspected to play a major role in the Prader-Willi syndrome (PWS), yet its molecular function...
The eutherian-specific SNORD116 family of repeated box C/D snoRNA genes is suspected to play a major role in the Prader-Willi syndrome (PWS), yet its molecular function remains poorly understood. Here, we combined phylogenetic and molecular analyses to identify candidate RNA targets. Based on the analysis of several eutherian orthologs, we found evidence of extensive birth-and-death and conversion events during SNORD116 gene history. However, the consequences for phylogenetic conservation were heterogeneous along the gene sequence. The standard snoRNA elements necessary for RNA stability and association with dedicated core proteins were the most conserved, in agreement with the hypothesis that SNORD116 generate genuine snoRNAs. In addition, one of the two antisense elements typically involved in RNA target recognition was largely dominated by a unique sequence present in at least one subset of gene paralogs in most species, likely the result of a selective effect. In agreement with a functional role, this ASE exhibited a hybridization capacity with putative mRNA targets that was strongly conserved in eutherians. Moreover, transient downregulation experiments in human cells showed that Snord116 controls the expression and splicing levels of these mRNAs. The functions of two of them, diacylglycerol kinase kappa and Neuroligin 3, extend the description of the molecular bases of PWS and reveal unexpected molecular links with the Fragile X syndrome and autism spectrum disorders.
Topics: Humans; Phylogeny; Prader-Willi Syndrome; RNA Stability; RNA, Messenger; RNA, Small Nucleolar
PubMed: 34893870
DOI: 10.1093/molbev/msab348 -
Journal of Clinical Research in... Aug 2021To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey.
OBJECTIVE
To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey.
METHODS
The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated.
RESULTS
The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged.
CONCLUSION
The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.
Topics: Adolescent; Adolescent Development; Age Factors; Body Height; Body Mass Index; Child; Child Development; Child, Preschool; Female; Genetic Predisposition to Disease; Human Growth Hormone; Humans; Infant; Infant, Newborn; Male; Phenotype; Prader-Willi Syndrome; Retrospective Studies; Treatment Outcome; Turkey
PubMed: 33565750
DOI: 10.4274/jcrpe.galenos.2021.2020.0228 -
Orphanet Journal of Rare Diseases Feb 2023Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and...
BACKGROUND
Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients' care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results.
MATERIALS AND METHODS
The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality.
RESULTS
A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019-2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment.
CONCLUSIONS
The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Chromosomes, Human, Pair 15; Delayed Diagnosis; Italy; Prader-Willi Syndrome; Quality of Life; Registries
PubMed: 36793093
DOI: 10.1186/s13023-023-02633-5 -
Advances in Pediatrics Aug 2016
Review
Topics: Adrenal Insufficiency; Bariatric Surgery; Body Composition; Child; Child Behavior Disorders; Diabetes Mellitus, Type 2; Diet, Reducing; Dwarfism; Energy Metabolism; Ghrelin; Gonadal Steroid Hormones; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hyperphagia; Hypogonadism; Hypothyroidism; Mental Disorders; Obesity; Prader-Willi Syndrome; Sleep Wake Disorders
PubMed: 27426895
DOI: 10.1016/j.yapd.2016.04.005