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Clinical Endocrinology Feb 2022The mainstay management of hyperphagia and obesity in Prader-Willi syndrome (PWS) relies on dietary restrictions, strict supervision and behavioural modifications, which...
OBJECTIVE
The mainstay management of hyperphagia and obesity in Prader-Willi syndrome (PWS) relies on dietary restrictions, strict supervision and behavioural modifications, which can be stressful for the patient and caregiver. There is no established pharmacological strategy to manage this aspect of PWS. Theoretically, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1-RA) used in patients with obesity and type 2 diabetes mellitus (T2DM) may be efficacious in weight and glycaemic control of PWS patients. We conducted a systematic review of the literature to summarize the evidence on the use of GLP1-RA in PWS patients.
DESIGN
Primary studies were searched in major databases using key concepts 'Prader-Willi syndrome' and 'GLP1 receptor agonist' and outcomes, 'weight control OR glycaemic control OR appetite regulation'.
RESULTS
Ten studies included, summarizing GLP1-RA use in 23 PWS patients (age, 13-37 years), who had used either exenatide (n = 14) or liraglutide (n = 9) over a duration of 14 weeks to 4 years. Sixteen (70%) of these patients had T2DM. Ten patients experienced improvement in body mass index, ranging from 1.5 to 16.0 kg/m , while improvement in HbA1c was seen in 19 of 23 cases, ranging between 0.3% and 7.5%. All five studies reporting appetite or satiety showed improvement in satiety levels. There were no reported serious side effects.
CONCLUSIONS
GLP1-RA appears safe in PWS patients and may have potential benefits for weight, glycaemic and appetite control. Nonetheless, we also highlight a significant gap in the literature on the lack of well-designed studies in this area, which limits the recommendation of GLP1-RA use in PWS patients at present.
Topics: Adolescent; Adult; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycemic Control; Humans; Liraglutide; Prader-Willi Syndrome; Young Adult
PubMed: 34448208
DOI: 10.1111/cen.14583 -
Tijdschrift Voor Psychiatrie 2021Prader-Willi syndrome (PWS) is a genetic syndrome characterized by dysmorphic features and endocrine, cognitive and psychiatric problems. Psychiatric problems interfere...
BACKGROUND
Prader-Willi syndrome (PWS) is a genetic syndrome characterized by dysmorphic features and endocrine, cognitive and psychiatric problems. Psychiatric problems interfere with the transition from pediatric to adult care. Psychiatric expertise is needed to facilitate this transition.
AIM
To provide a literature review on the prevalence and clinical presentation of psychiatric disorders in adults with PWS.
METHOD
A systematic literature review following the PRISMA-guidelines.
RESULTS
Thirty-three articles were included. Most adults with PWS had a specific behavioral profile with disruptive, autistic and compulsive characteristics. Psychotic symptoms occured in one third of adults with PWS, mostly in patients with maternal uniparental disomy. Mood disorders were present in 10 to 20% of adults with PWS and often accompanied by psychotic features. Studies were limited and heterogeneous in samples and methods.
CONCLUSION
There is a broad spectrum of psychiatric symptoms in adults with PWS. The clinical presentation does not fully fit within the DSM categories and shows differences between genetic subgroups. Longitudinal studies assessing the psychiatric symptoms with standardized methods are needed to improve practices on diagnosing, prevention, and treatment.
Topics: Adult; Child; Humans; Longitudinal Studies; Prader-Willi Syndrome; Psychotic Disorders; Transition to Adult Care
PubMed: 34231862
DOI: No ID Found -
Journal of Clinical Medicine Jun 2021Physical activity (PA) is an important aspect of the management of patients with Prader-Willi syndrome (PWS). However, the day-to-day implementation of PA programs is... (Review)
Review
Physical activity (PA) is an important aspect of the management of patients with Prader-Willi syndrome (PWS). However, the day-to-day implementation of PA programs is particularly challenging in these patients. This systematic review aimed (1) to describe habitual PA and sedentary behavior and (2) to assess the effects of PA interventions and to describe their implementation process, in children and adults with PWS. A systematic search of controlled trials, single-group interventions, observational, and qualitative studies published up to December 2020 was performed. Twenty-five studies were included. Habitual PA was found to be lower in patients with PWS compared to controls without obesity or with non-syndromic obesity. Habitual PA was positively associated with lean body mass and bone parameters in children with PWS, and these finding were strengthened by intervention studies reporting an increase in both outcomes after a PA program. PA programs also improved physical function (muscle strength, walking distance, and coordination), without significant effect on weight and fat mass. Attendance to exercise sessions was usually high and no serious adverse effect was reported. In conclusion, supervised PA programs are beneficial for children and adults with PWS. Support should be provided to families to facilitate their implementation in real-life settings.
PubMed: 34200339
DOI: 10.3390/jcm10112528 -
The Journal of Clinical Endocrinology... Sep 2021Features of Prader-Willi syndrome (PWS) overlap with features of growth hormone (GH) deficiency, like small hands and feet, short stature, increased body fat, and low... (Meta-Analysis)
Meta-Analysis
CONTEXT
Features of Prader-Willi syndrome (PWS) overlap with features of growth hormone (GH) deficiency, like small hands and feet, short stature, increased body fat, and low muscle mass and strength. In children with PWS, GH treatment (GHt) improves physical health and cognition. GHt has become the standard of care in PWS children, but in adults this is not yet the case.
OBJECTIVE
This work aims to provide an overview of the current knowledge on GHt in PWS adults.
METHODS
Medline, Embase, and the Cochrane Central Register of Controlled Trials databases were searched. Study selection included randomized clinical trials (RCTs) and nonrandomized (un)controlled trials (NRCTs) that reported data for adults with PWS, who received GHt for at least 6 months. Data on body composition, body mass index (BMI), cardiovascular end points, bone, cognitive function, quality of life, and safety were extracted.
RESULTS
Nine RCTs and 20 NRCTs were included. Body composition improved during 12 months of GHt with an increase in mean (95% CI) lean body mass of 1.95 kg (0.04 to 3.87 kg) and a reduction of mean (95% CI) fat mass of -2.23% (-4.10% to -0.36%). BMI, low-density lipoprotein cholesterol levels, fasting glucose levels, and bone mineral density did not change during GHt. There were no major safety issues.
CONCLUSION
GHt appears to be safe and improves body composition in adults with PWS. Because poor body composition is closely linked to the observed high incidence of cardiovascular morbidity in adults with PWS, improving body composition might reduce cardiovascular complications in this vulnerable patient group.
Topics: Adolescent; Adult; Body Composition; Body Mass Index; Female; Human Growth Hormone; Humans; Male; Middle Aged; Prader-Willi Syndrome; Quality of Life; Treatment Outcome; Young Adult
PubMed: 34105729
DOI: 10.1210/clinem/dgab406 -
Growth Hormone & IGF Research :... 2021We sought to obtain a better understanding of the burden of short stature using a systematic literature review.
OBJECTIVE
We sought to obtain a better understanding of the burden of short stature using a systematic literature review.
METHODS
Studies of the burden of short stature, of any cause in adults and children, were searched using Embase, MEDLINE and Cochrane databases in April 2020, capturing publications from 2008 onwards. Case series and populations with adult-onset growth hormone deficiency (GHD) were excluded.
RESULTS
Of 1684 publications identified, 41 studies (33 in children, 8 in adults) were included. All studies assessed human burden. Most study populations in children included short stature due to GHD, idiopathic short stature (ISS) and short stature after being born small for gestational age (SGA). In these populations, four studies showed that quality of life (QoL) in children with short stature was significantly worse than in children with normal stature. A significant association between QoL and short stature was observed in children with chronic kidney disease (CKD) (3 studies), achondroplasia (1 study) and transfusion-dependent β-thalassaemia (1 study), and in samples with mixed causes of short stature (3 studies). Three studies (one in GHD/ISS/SGA and two in CKD) found no significant association between short stature and QoL, and several studies did not report statistical significance. Approximately half of adult studies showed that QoL was reduced with short stature, and the other half showed no association. Two studies, one in adults with Prader-Willi syndrome and one in children with GHD, suggested a potential association between short stature and poorer cognitive outcomes. Three studies demonstrated an increased caregiver burden in parents of children with short stature.
CONCLUSIONS
Evidence suggests that, compared with those with normal stature, children and adults with short stature of any cause may experience poorer QoL. Further research could extend our understanding of the human burden in this field.
Topics: Achondroplasia; Adult; Body Height; Caregiver Burden; Child; Cost of Illness; Growth Disorders; Human Growth Hormone; Humans; Infant, Small for Gestational Age; Parents; Quality of Life; Renal Insufficiency, Chronic; beta-Thalassemia
PubMed: 33975197
DOI: 10.1016/j.ghir.2021.101392 -
Sleep Medicine Reviews Jun 2021Individuals with Rare Genetic Neurodevelopmental Disorders (RGND) present with significant sleep problems and circadian rhythm abnormalities of uncertain aetiology.... (Review)
Review
Individuals with Rare Genetic Neurodevelopmental Disorders (RGND) present with significant sleep problems and circadian rhythm abnormalities of uncertain aetiology. Abnormal melatonin secretion may play a role in sleep disturbance in individuals with higher incidence developmental disabilities, however, RGND research is limited. This review compared the melatonin profiles in a range of RGND with that of the general population and considered the impact of any differences on sleep. A systematic search identified 19 studies that met inclusion criteria. Each study was examined to extract data relating to the study design, participant characteristics, objectives, sleep measures and results, and melatonin measures and findings. Studies were evaluated using the BIOCROSS quality appraisal tool. Nine studies focussed on Smith-Magenis syndrome (SMS), the rest included individuals with Angelman (AS), Fragile-X (FXS), Prader-Willi (PWS), septo-optic dysplasia, PAX6/WAGR and Williams (WS) syndromes (N = 349). Individuals with RGND present with a range of sleep problems, particularly dyssomnias. The melatonin profile varied within and between RGND, with low nocturnal melatonin levels commonly reported. Understanding the relationship between specific sleep and melatonin parameters within RGND may help inform sleep intervention.
Topics: Humans; Melatonin; Neurodevelopmental Disorders; Sleep; Sleep Wake Disorders; Smith-Magenis Syndrome
PubMed: 33561678
DOI: 10.1016/j.smrv.2021.101433 -
Clinical Endocrinology Apr 2021Despite clear benefits in the management of children with Prader-Willi syndrome (PWS), the role of growth hormone (GH) in adults is unclear. The aim of this study was to...
OBJECTIVE
Despite clear benefits in the management of children with Prader-Willi syndrome (PWS), the role of growth hormone (GH) in adults is unclear. The aim of this study was to conduct a systematic review to evaluate the effects of GH on body composition, bone health and cardiovascular health in adults with PWS.
DESIGN
A systematic computerized literature search of the PubMed database was conducted by two independent reviewers. Inclusion criteria were individuals over the age of 16 years with a genetic diagnosis of PWS who had received GH therapy, together with assessment of body composition, bone health or cardiovascular health.
RESULTS
Twenty full-text papers met the inclusion criteria, encompassing 364 unique patients. No differences in body mass index (BMI) were noted, although 2 studies reported increased BMI after GH cessation. Data demonstrated statistically significant increases in lean body mass and reductions in percentage fat mass. Studies reported inconsistent effects of GH on cholesterol and echocardiography parameters. No studies reported differences in bone mineral density, although one reported improved bone geometry. Minor adverse events including pretibial oedema, headache and transient impaired glucose tolerance were reported in 7 studies.
CONCLUSIONS
These data suggest that GH is safe and well tolerated in adults with PWS, with evidence of improvement in body composition. Further longitudinal studies are still required to investigate the effects of GH on bone and cardiovascular health. Where GH is used in adults with PWS, this should be managed by a specialist multidisciplinary team with regular monitoring initiated.
Topics: Adolescent; Adult; Body Composition; Bone Density; Child; Growth Hormone; Human Growth Hormone; Humans; Prader-Willi Syndrome
PubMed: 33296095
DOI: 10.1111/cen.14372 -
The Laryngoscope Apr 2021Prader-Willi syndrome (PWS) increases the risk of obstructive sleep apnea (OSA) due to obesity, hypotonia, and abnormal ventilatory responses. We evaluated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Prader-Willi syndrome (PWS) increases the risk of obstructive sleep apnea (OSA) due to obesity, hypotonia, and abnormal ventilatory responses. We evaluated post-adenotonsillectomy complications, polysomnography changes, and quality of life in children with OSA and PWS.
STUDY DESIGN
Systematic review and meta-analysis.
METHODS
We conducted a systematic review and meta-analysis by searching PubMed, Embase, Cochrane, Web of Science, and Scopus. Two researchers independently reviewed studies about adenotonsillectomy for OSA in patients <21 years with PWS. We extracted study design, patient numbers, age, complications, polysomnography, and quality of life. We pooled postoperative changes in apnea hypopnea index (AHI) for meta-analysis. We applied Methodological Index for Nonrandomized Studies (MINORS) criteria to assess study quality.
RESULTS
The initial search yielded 169 studies. We included 68 patients from eight studies with moderate to high risk of bias. Six studies reported on complications and 12 of 51 patients (24%) had at least one. Velopharyngeal insufficiency was the most commonly reported complication (7/51, 14%). We included seven studies in meta-analysis. Mean postoperative improvement in AHI was 7.7 (95% CI: 4.9-10.5). Postoperatively 20% (95% CI: 3%-43%) had resolution of OSA with AHI < 1.5 while 67% (95% CI: 50%-82%) had improvement from severe/moderate OSA to mild/resolved (AHI < 5). Two studies evaluated quality of life and demonstrated improvement.
CONCLUSIONS
Children with PWS undergoing adenotonsillectomy for OSA have a substantial risk of postoperative complications that may require additional interventions, especially velopharyngeal insufficiency. Despite improvements in polysomnography and quality of life, many patients had residual OSA. This information can be used to counsel families when considering OSA treatment options. Laryngoscope, 131:898-906, 2021.
Topics: Adenoidectomy; Child; Humans; Polysomnography; Postoperative Complications; Prader-Willi Syndrome; Quality of Life; Sleep Apnea, Obstructive; Tonsillectomy
PubMed: 33026674
DOI: 10.1002/lary.28922 -
BMJ Paediatrics Open 2020Growth hormone (GH) treatment is currently recommended in Prader-Willi syndrome (PWS) patients.
BACKGROUND
Growth hormone (GH) treatment is currently recommended in Prader-Willi syndrome (PWS) patients.
OBJECTIVES
To evaluate the impact (efficacy and safety) of the use of recombinant human GH (rhGH) as a treatment for PWS.
METHOD
We performed a systematic review and, where possible, meta-analysis for the following outcomes: growth, body mass index, body composition, cognitive function, quality of life, head circumference, motor development/strength, behaviour and adverse effects. We included all PWS patients, with all types of genetic defects and with or without GH deficiency, who participated in rhGH studies performed in infancy, childhood and adolescence, that were either randomised controlled trials (RCTs) (double-blinded or not) or non-randomised controlled trials (NRCTs) (cohort and before and after studies). The databases used were MEDLINE, Embase and Cochrane Central.
RESULTS
In 16 RCTs and 20 NRCTs selected, the treated group had an improvement in height (1.67 SD scores (SDS); 1.54 to 1.81); body mass index z-scores (-0.67 SDS; -0.87 to -0.47) and fat mass proportion (-6.5% SDS; -8.46 to -4.54) compared with the control group. Data about cognition could not be aggregated. Based on high quality evidence, rhGH treatment favoured an improvement of stature, body composition and body mass index, modifying the disease's natural history; rhGH treatment may also be implicated in improved cognition and motor development in PWS patients at a young age.
ETHICS AND DISSEMINATION
The current review was approved by the ethical committee of our institution. The results will be disseminated through conference presentations and publications in peer-reviewed journals.
PROSPERO REGISTRATION NUMBER
CRD42019140295.
PubMed: 32411831
DOI: 10.1136/bmjpo-2019-000630 -
Journal of the American Academy of... Sep 2020The behavioral phenotype of neurogenetic disorders associated with intellectual disability often includes psychiatric comorbidity. The objectives of this systematic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The behavioral phenotype of neurogenetic disorders associated with intellectual disability often includes psychiatric comorbidity. The objectives of this systematic review and meta-analysis were to systematically review the prevalence of psychiatric disorders and symptoms in children and adolescents with these disorders and compare phenotypic signatures between syndromes.
METHOD
MEDLINE and PsycINFO databases were searched for articles from study inception to December 2018. Eligible articles were peer reviewed, were published in English, and reported prevalence data for psychiatric disorders and symptoms in children and adolescents aged 4 to 21 years using a formal psychiatric assessment or a standardized assessment of mental health symptoms. Pooled prevalence was determined using a random-effects meta-analysis in studies with sufficient data. Prevalence estimates were compared with general population data using a test of binomial proportions.
RESULTS
Of 2,301 studies identified for review, 39 articles were included in the final pool, which provided data on 4,039 children and adolescents. Ten syndromes were represented, and five were predominant: Down syndrome, 22q11.2 deletion syndrome, fragile X syndrome, Williams syndrome, and Prader-Willi syndrome. The Child Behavior Checklist was the most commonly used assessment tool for psychiatric symptoms. The pooled prevalence with total scores above the clinical threshold was lowest for Down syndrome (32% [95% confidence interval, 19%-44%]) and highest for Prader-Willi syndrome (74% [95% CI, 65%-82%]) with each syndrome associated with significantly higher prevalence than in the general population. Parallel trends were observed for the internalizing and externalizing domains and social subscale scores.
CONCLUSION
Differential vulnerability for psychiatric phenotype expression across the disorders was observed. Syndromes with higher levels of social ability or competence appear to offer relative protection against developing psychopathology. This preliminary finding merits further exploration.
Topics: Adolescent; Adult; Child; Child, Preschool; Comorbidity; Humans; Intellectual Disability; Mental Disorders; Mental Health; Prader-Willi Syndrome; Prevalence; Young Adult
PubMed: 31945412
DOI: 10.1016/j.jaac.2020.01.006