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Pediatric Endocrinology Reviews : PER Mar 2015Prader-Willi Syndrome (PWS) is one of the most common genetic causes of obesity. The phenotype of obesity in PWS is unique and characterized by hyperphagia, earlier meal... (Review)
Review
Prader-Willi Syndrome (PWS) is one of the most common genetic causes of obesity. The phenotype of obesity in PWS is unique and characterized by hyperphagia, earlier meal initiation, delayed meal termination, reduced energy expenditure, abnormal gut hormone profiles, as well as irregular responses to food in areas of the brain associated with satiety and reward. Management of obesity is necessary to avoid major morbidity. The relentless food-seeking behavior associated with PWS such as stealing, hoarding food, eating inedibles, and lying about eating, can cause turmoil both inside and outside of the home. Management is challenging for both patients and caretakers, but at this time there are limited medical therapies available besides dietary restriction and behavior management. However, current research shows promise for discovery of additional treatment options for hyperphagia and obesity management in PWS.
Topics: Animals; Humans; Hyperphagia; Obesity; Prader-Willi Syndrome; Weight Reduction Programs
PubMed: 25962207
DOI: No ID Found -
The Biochemical Journal Jun 2017Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated... (Review)
Review
Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader-Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SHFYNG). MAGEL2 is highly expressed in the hypothalamus and plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway. MAGEL2 is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme. The AGEL2-P7-RIM27 (or MUST) complex facilitates the retromer recycling pathway through ubiquitination and activation of the WASH actin nucleation promoting factor. This review provides an overview of the MAGE protein family of ubiquitin ligases regulators and details the molecular and cellular role of MAGEL2 in ubiquitination, actin regulation and endosomal sorting processes, as well as MAGEL2 implications in PWS and SHFYNG disorders. The physiological functions of MAGEL2, elucidated through the study of knockout mouse models, are also discussed.
Topics: Endosomes; Humans; Prader-Willi Syndrome; Protein Transport; Proteins; Ubiquitination
PubMed: 28626083
DOI: 10.1042/BCJ20160616 -
Current Opinion in Psychiatry Mar 2015To provide a review of the recent advances in the diagnosis and treatment of psychiatric disorders in Prader-Willi syndrome (PWS). (Review)
Review
PURPOSE OF REVIEW
To provide a review of the recent advances in the diagnosis and treatment of psychiatric disorders in Prader-Willi syndrome (PWS).
RECENT FINDINGS
Research in the last 12 months has provided a descriptive prognosis of psychosis in PWS and highlighted the possible genes associated with the increased risk of psychosis for those with maternal uniparental disomy (mUPD). Several studies investigating social and communication skills have shown people with PWS to have difficulty with core, receptive and expressive language skills, interpreting emotional valence in faces, playing with children of their own age, understanding personal space and a developmental delay in the theory of mind. These social and communication deficits are often more pronounced in those with mUPD. Two recent clinical trials of oxytocin provide mixed results and highlight the need for an improved understanding of the neurobiological characteristics of the PWS brain. A recent pilot study suggests N-acetylcysteine may be a viable treatment for skin picking.
SUMMARY
Recent advances have contributed to our understanding of the emotional and behavioural problems associated with PWS, and provided directions for further research.
Topics: Child; Child Behavior Disorders; Cognition Disorders; Humans; Prader-Willi Syndrome; Randomized Controlled Trials as Topic
PubMed: 25599341
DOI: 10.1097/YCO.0000000000000135 -
Pediatrics International : Official... 2023Prader-Willi syndrome (PWS) is suspected at birth if extreme hypotonia, difficulty in feeding, hypogonadism, and failure to thrive are present. Genetic diagnosis of PWS...
BACKGROUND
Prader-Willi syndrome (PWS) is suspected at birth if extreme hypotonia, difficulty in feeding, hypogonadism, and failure to thrive are present. Genetic diagnosis of PWS can generally be made within the first few months of life; however, a delayed diagnosis of PWS is frequently reported. Although the clinical characteristics of perinatal and neonatal patients with PWS have been reported, there are no such reports on the clinical characteristics of these patients in Japan.
METHODS
This retrospective, single-center study involved 177 Japanese patients with PWS and their medical data regarding the perinatal and neonatal periods were evaluated.
RESULTS
The median maternal age at birth was 34 years; 12.7% of the mothers had a history of assisted reproductive technology (ART). Of the mothers, 13.5% reported polyhydramnios and 4.3% had oligohydramnios. Decreased fetal movement during pregnancy was reported by 76% of the mothers. A total of 60.5% of patients were born by cesarean section. Genetic subtypes included deletions (66.1%), uniparental disomy (31.0%), imprinting defects (0.6%), and other or unknown subtypes (2.3%). The median birth length was 47.5 cm and the median birthweight was 2476 g. Of the 160 patients, 14 (8.8%) were classified as small for gestational age. Most patients had hypotonia (98.8%), and 89.3% required gavage feeding at birth. Breathing problems, congenital heart disease, and undescended testis were noted in 33.1%, 7.0%, and 93.5% of patients, respectively.
CONCLUSION
In our study, higher rates of ART, polyhydramnios, decreased fetal movements, cesarean section, hypotonia, feeding difficulties, and undescended testis were observed in PWS.
Topics: Infant, Newborn; Male; Humans; Pregnancy; Female; Adult; Prader-Willi Syndrome; Muscle Hypotonia; Cesarean Section; Cryptorchidism; Polyhydramnios; Japan; Retrospective Studies
PubMed: 36975754
DOI: 10.1111/ped.15540 -
The Journal of Clinical Endocrinology... Jun 2023
Topics: Humans; Child; Adolescent; Prader-Willi Syndrome; Liraglutide; Obesity
PubMed: 36638011
DOI: 10.1210/clinem/dgad017 -
Best Practice & Research. Clinical... Dec 2016Prader-Willi syndrome (PWS) results from under-expression of the paternally-derived chromosomal region 15q11-13. Growth failure is a recognized feature of PWS, and both... (Review)
Review
Prader-Willi syndrome (PWS) results from under-expression of the paternally-derived chromosomal region 15q11-13. Growth failure is a recognized feature of PWS, and both quantitative and qualitative defects of the GH/IGF-I axis revealing GH deficiency (GHD) have been demonstrated in most children with PWS. In PWS adults, criteria for GHD are biochemically fulfilled in 8-38% of the studied cohorts. Published data support benefits of early institution of GH therapy (GHT) in PWS children, with positive effects on statural growth, body composition, metabolic homeostasis, and neurocognitive function. Like in pediatric PWS, GHT also yields beneficial effects on lean and body fat, exercise capacity, and quality of life of PWS adults. Although GHT has been generally administered safely in PWS children and adults, careful surveillance of risks is mandatory during prolonged GH replacement for all PWS individuals.
Topics: Hormone Replacement Therapy; Human Growth Hormone; Humans; Prader-Willi Syndrome
PubMed: 27974191
DOI: 10.1016/j.beem.2016.11.003 -
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 -
Orphanet Journal of Rare Diseases Jun 2022Prader-Willi syndrome (PWS) is a complex and multisystem neurobehavioral disease, which is caused by the lack of expression of paternally inherited imprinted genes on... (Review)
Review
Prader-Willi syndrome (PWS) is a complex and multisystem neurobehavioral disease, which is caused by the lack of expression of paternally inherited imprinted genes on chromosome15q11.2-q13.1. The clinical manifestations of PWS vary with age. It is characterized by severe hypotonia with poor suck and feeding difficulties in the early infancy, followed by overeating in late infancy or early childhood and progressive development of morbid obesity unless the diet is externally controlled. Compared to Western PWS patients, Chinese patients have a higher ratio of deletion type. Although some rare disease networks, including PWS Cooperation Group of Rare Diseases Branch of Chinese Pediatric Society, Zhejiang Expert Group for PWS, were established recently, misdiagnosis, missed diagnosis and inappropriate intervention were usually noted in China. Therefore, there is an urgent need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy. Our purpose is to evaluate the current literature and evidences on diagnosis and management of PWS in order to provide evidence-based guidelines for this disease, specially from China.
Topics: Child; Child, Preschool; China; Early Diagnosis; Humans; Muscle Hypotonia; Prader-Willi Syndrome; Quality of Life
PubMed: 35698200
DOI: 10.1186/s13023-022-02302-z -
Biochemical and Biophysical Research... Aug 2024Prader-Willi syndrome (PWS) is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13. This syndrome also includes...
Prader-Willi syndrome (PWS) is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13. This syndrome also includes endocrine dysfunction, leading to short stature, hypogonadism, and obscure hyperphagia. Although recent progress has been made toward understanding the genetic basis for PWS, the molecular mechanisms underlying its pathology in obesity remain unclear. In this study, we examined the adipocytic characteristics of two PWS-induced pluripotent stem cell (iPSC) lines: those with the 15q11-q13 gene deletion (iPWS cells) and those with 15q11-q13 abnormal methylation (M-iPWS cells). The transcript levels of the lipid-binding protein aP2 were decreased in iPWS and M-iPWS adipocytes. Flow-cytometry analysis showed that PWS adipocytes accumulated more lipid droplets than did normal individual adipocytes. Furthermore, glucose uptake upon insulin stimulation was attenuated compared to that in normal adipocytes. Overall, our results suggest a significantly increased lipid content and defective in glucose metabolism in PWS adipocytes.
Topics: Prader-Willi Syndrome; Adipocytes; Humans; Induced Pluripotent Stem Cells; Glucose; Chromosomes, Human, Pair 15; Fatty Acid-Binding Proteins; Cell Line; DNA Methylation; Gene Deletion; Lipid Metabolism; Insulin
PubMed: 38776833
DOI: 10.1016/j.bbrc.2024.150124 -
Tijdschrift Voor Psychiatrie 2021
Topics: Adult; Comorbidity; Human Growth Hormone; Humans; Prader-Willi Syndrome
PubMed: 34851524
DOI: No ID Found