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Current Obesity Reports Dec 2022Prader-Willi syndrome (PWS) is a rare and complex genetic disorder with multiple effects on the metabolic, endocrine, and neurological systems, as well as behavioral and... (Review)
Review
PURPOSE OF REVIEW
Prader-Willi syndrome (PWS) is a rare and complex genetic disorder with multiple effects on the metabolic, endocrine, and neurological systems, as well as behavioral and intellectual difficulties. Despite advances in understanding the genetic basis of obesity in PWS, there are conflicting data on its management. Therefore, the present manuscript aims to provide an update on the nutritional treatment and pharmacological approach in adult patients with PWS.
RECENT FINDINGS
The management of obesity in patients with PWS is challenging and requires the cooperation of an experienced multidisciplinary team, including the nutritionist. An adequate clinical evaluation including nutritional and biochemical parameters should be performed to tailor the best therapeutic strategy. Both lifestyle and pharmacological interventions may represent useful strategies to prevent the high rate of morbidity and mortality related to PWS. The use of bariatric surgery is still controversial. Although it is imperative to adopt an obesity prevention strategy in childhood, there is promising evidence for the treatment of obesity in adulthood with current obesity medications in conjunction with lifestyle interventions.
Topics: Humans; Adult; Prader-Willi Syndrome
PubMed: 36063285
DOI: 10.1007/s13679-022-00478-w -
Expert Review of Endocrinology &... Mar 2021: Prader-Willi syndrome (PWS) is the most well-known condition of genetic obesity. Over the past 20 years, advances have been achieved in the diagnosis and treatment of... (Review)
Review
: Prader-Willi syndrome (PWS) is the most well-known condition of genetic obesity. Over the past 20 years, advances have been achieved in the diagnosis and treatment of PWS with a significant improvement in prognosis.: This review focuses on the benefits of multidisciplinary approach in children and adolescents with PWS. In particular, the neonatologist and geneticist play a key role in early diagnosis and the clinical follow-up of the PWS patient must be guaranteed by a team including pediatric endocrinologist, psychologist, nutritionist/dietician, neurologist/neuropsychiatrist, sleep specialist, ears, nose and throat specialist (ENT), lung specialist, dentist, orthopedist and ophthalmologist and, eventually, gastroenterologist. We searched PubMed and critically summarized what has been reported in the last 10 years on PWS.: The multidisciplinary care in association with an early diagnosis and GH treatment postpones overweight development and decreases prevalence of obesity in individuals with PWS. Further prognostic improvements are expected through the selection of teams particularly experienced in the management of individuals with PWS and the discovery of new drugs.
Topics: Adolescent; Child; Early Diagnosis; Humans; Obesity; Prader-Willi Syndrome; Prognosis
PubMed: 33724138
DOI: 10.1080/17446651.2021.1898375 -
Acta Physiologica (Oxford, England) Mar 2021Ghrelin is a gastric hormone with multiple physiological functions, including the stimulation of food intake and adiposity. It is well established that circulating... (Review)
Review
Ghrelin is a gastric hormone with multiple physiological functions, including the stimulation of food intake and adiposity. It is well established that circulating ghrelin levels are closely associated with feeding patterns, rising strongly before a meal and lowering upon food intake. However, the mechanisms underlying the modulation of ghrelin secretion are not fully understood. The purpose of this review is to discuss current knowledge on the circadian oscillation of circulating ghrelin levels, the neural mechanisms stimulating fasting ghrelin levels and peripheral mechanisms modulating postprandial ghrelin levels. Furthermore, the therapeutic potential of targeting the ghrelin pathway is discussed in the context of the treatment of various metabolic disorders, including obesity, type 2 diabetes, diabetic gastroparesis and Prader-Willi syndrome. Moreover, eating disorders including anorexia nervosa, bulimia nervosa and binge-eating disorder are also discussed.
Topics: Diabetes Mellitus, Type 2; Eating; Ghrelin; Humans; Obesity; Postprandial Period; Prader-Willi Syndrome
PubMed: 33249751
DOI: 10.1111/apha.13588 -
American Journal of Medical Genetics.... Nov 2022Prader-Willi syndrome is a complex neurodevelopmental genetic imprinting disorder with severe congenital hypotonia, failure to thrive with learning and behavioral...
Prader-Willi syndrome is a complex neurodevelopmental genetic imprinting disorder with severe congenital hypotonia, failure to thrive with learning and behavioral problems, and hyperphagia with obesity developing in early childhood. Those with the typical 15q11-q13 Type I deletion compared with the smaller Type II deletion have more severe neurobehavioral problems and differ by the absence of four genes in the 15q11.2 BP1-BP2 region. Two of the genes encode magnesium transporters supporting brain and neurological function and we report on magnesium levels in the two deletion groups of PWS participants. We measured baseline plasma magnesium and analyzed data from a PWS cohort with and without the Type I or Type II deletion. Significantly lower plasma magnesium levels were found in PWS participants with the larger Type I deletion and more so with females with Type I deletion compared with females having the Type II deletion, although magnesium levels remained within normal range in both subgroups. Those with PWS and the larger 15q11-q13 Type I deletion were more clinically affected than those with the smaller Type II deletion. Two of the four genes missing in those with the larger deletion code for magnesium transporters and may impact magnesium levels. Our study showed lower magnesium levels in those with the larger deletion which could contribute to neurobehavioral differences seen in the two separate 15q11-q13 deletion subtypes and in addition affect both glucose and insulin metabolism impacting comorbidities but will require more research.
Topics: Child, Preschool; Chromosomes, Human, Pair 15; Female; Genomic Imprinting; Glucose; Humans; Insulins; Magnesium; Prader-Willi Syndrome
PubMed: 36190479
DOI: 10.1002/ajmg.a.62928 -
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 -
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 -
Adolescent Health, Medicine and... 2020Prader-Willi syndrome (PWS) is a complex, multisystem neurodevelopmental disorder affecting approximately 1 in 25,000 live births. PWS is caused by absence of expression... (Review)
Review
Prader-Willi syndrome (PWS) is a complex, multisystem neurodevelopmental disorder affecting approximately 1 in 25,000 live births. PWS is caused by absence of expression of paternally inherited imprinted genes on chromosome 15q11-q13. The syndrome typically occurs due to one of three genetic mechanisms: paternal deletion of involved genes, maternal uniparental disomy, or imprinting center defects. These genetic anomalies lead to well-described clinical phenotype that includes hypotonia, hypothalamic dysfunction, social and behavioral issues, life-threatening hyperphagia, and elevated probability of obesity. Adolescents with PWS are at the highest risk for development of life-threatening obesity due to increased access to food, decreased physical activity, and hyperphagia. Currently, the only treatment for the hyperphagia is environmental control, including locked kitchens and continuous supervision of the affected individual. Caloric intake must be restricted to prevent obesity, which subsequently increases the hunger drive even more. Research and clinical practice have demonstrated that increasing physical activity along with insuring a well-balanced, nutritionally dense diet can improve overall weight control in adolescents with PWS.
PubMed: 32922110
DOI: 10.2147/AHMT.S214893 -
Acta Paediatrica (Oslo, Norway : 1992) May 2021Prader-Willi syndrome is a complex condition requiring constant care and supervision of the affected child.
UNLABELLED
Prader-Willi syndrome is a complex condition requiring constant care and supervision of the affected child.
AIM
To evaluate quality of life and caregiver burden in children with Prader-Willi syndrome.
METHODS
All children with Prader-Willi syndrome, attending a tertiary referral centre, were invited to participate (n = 44). Quality of life was evaluated using the PedsQL questionnaire. Family impact modules and parent proxy reports evaluated the impact on the quality of life of the child and family. Additional challenges were captured using a burden questionnaire.
RESULTS
Nineteen children participated. Median age was 7.9 years (0.6-18.1 years). Majority were female (n = 14, 74%). Median age at diagnosis was 2.5 weeks (range birth-2 years 8 months). Growth hormone treatment was in place for the majority (n = 14, 74%). Increased weight and age were identified as significantly impacting on family functioning and relationships. Parents perceived increased weight and age to have a significant negative impact on their child's psychosocial health and social functioning. Caregivers of children >12 years reported an increased burden of care. Disruption to routines, restriction of social activities and psychological difficulties were reported as increasing caregiver burden.
CONCLUSION
Prader-Willi syndrome impacts significantly on quality of life for both the affected child and the family.
Topics: Caregiver Burden; Caregivers; Child; Female; Humans; Infant, Newborn; Male; Prader-Willi Syndrome; Quality of Life; Surveys and Questionnaires
PubMed: 33378107
DOI: 10.1111/apa.15738 -
Journal of Pediatric Orthopedics. Part B Nov 2023Although scoliosis is commonly seen in patients with Prader-Willi syndrome, the patterns and extent of the deformity may change along their growth. Increased body weight...
Although scoliosis is commonly seen in patients with Prader-Willi syndrome, the patterns and extent of the deformity may change along their growth. Increased body weight is another issue in these patients, and its relationship with scoliosis is still controversial. The aim of this study was to evaluate scoliosis in patients with PWS, and its relationship with BMI. This was a retrospective cohort study in which a series of radiographic images and BMI from each patient were collected, and the data were rearranged following the age at which they were recorded. These patients were subsequently labeled as non-Scoliotic (<10°), Moderate (10° - 39°), and Severe (≥40°) according to their final Cobb angle, also as Normal (≤85%), Overweight (86%-95%), and Obese (≥95%) according to final BMI percentage. Thirty-four patients with age from 1 to 20 years old were recruited for this study, and the mean length of follow-up was 6.6 years. The prevalence of scoliosis was 71% (24 patients in Moderate, and 9 patients in Severe), and 65.6% were either overweight (11 patients) or obese (10 patients). The mean BMI percentage in non-scoliotic patients was 93.10 ± 13.84, which was significantly higher than that of the scoliotic groups ( P = 0.0180). When looking at the longitudinal change, the non-Scoliotic group had high BMI since childhood, and obese patients had less spine deformity also from early childhood. In this study, we found that the prevalence of scoliosis in Taiwanese population with PWS was 71% without gender preference. Not every patient had a high BMI, and obese patients seemed to have significantly less chance to develop scoliosis. Level III.
Topics: Humans; Child, Preschool; Infant; Child; Adolescent; Young Adult; Adult; Prader-Willi Syndrome; Scoliosis; Body Mass Index; Retrospective Studies; Overweight; Obesity
PubMed: 36445375
DOI: 10.1097/BPB.0000000000001031