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World Journal of Pediatrics : WJP May 2023Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader-Willi syndrome (PWS), the evidence of early rhGH...
Early recombinant human growth hormone treatment improves mental development and alleviates deterioration of motor function in infants and young children with Prader-Willi syndrome.
BACKGROUND
Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader-Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS.
METHODS
A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m/day for first four weeks, and 1 mg/m/day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed.
RESULTS
Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in < 9-month group were significantly higher than ≥ 9-month group. Mild to moderate severity adverse drug reactions were reported in six patients.
CONCLUSION
Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients < 9 months old.
Topics: Child; Child, Preschool; Humans; Infant; Anthropometry; Body Mass Index; Body Weight; Human Growth Hormone; Prader-Willi Syndrome; Recombinant Proteins
PubMed: 36564648
DOI: 10.1007/s12519-022-00653-y -
Obesity (Silver Spring, Md.) May 2022The aim of this study was to review bariatric procedure outcomes among patients with Prader-Willi syndrome (PWS), melanocortin 4 receptor (MC4R) mutations, Bardet-Biedl... (Review)
Review
OBJECTIVE
The aim of this study was to review bariatric procedure outcomes among patients with Prader-Willi syndrome (PWS), melanocortin 4 receptor (MC4R) mutations, Bardet-Biedl syndrome, and hypothalamic obesity.
METHODS
Systematic published literature review used the following search terms: "Prader-Willi syndrome," "Bardet-Biedl syndrome," "hyperphagia," "bariatric surgery," "MC4R"/"melanocortin 4 receptor", "hypothalamic obesity," and "bariatric procedure." Information collected included demographics, genetics, anthropometry, procedure type, outcomes, and complications, with inclusion of case series and clinical reports given the rarity of the disorders. For PWS, postoperative weight-change percentage and BMI up to 14 years following surgery were analyzed using general linear mixed models, with descriptive outcomes for other conditions.
RESULTS
A total of 54 publications were identified, with variable follow-up periods for 202 patients (114 with PWS, 43 with MC4R mutations, 7 with Bardet-Biedl syndrome, and 38 with hypothalamic obesity) among bariatric procedures. Weight loss of patients with PWS was greatest within 1 year of surgery, with weight-change percentage not significantly different from 0 at 5 years. Long-term results in other conditions were variable and featured suboptimal weight loss and increased reoperation risk.
CONCLUSIONS
Bariatric procedures among hyperphagic individuals, including those with PWS, report variable results and outcomes. Benefits of bariatric surgery may be less durable in hyperphagic disorders in comparison with other patients with severe obesity.
Topics: Bardet-Biedl Syndrome; Bariatric Surgery; Humans; Hyperphagia; Hypothalamic Diseases; Prader-Willi Syndrome; Treatment Outcome; Weight Loss
PubMed: 35416416
DOI: 10.1002/oby.23385 -
Frontiers in Endocrinology 2023Prader-Willi syndrome (PWS, OMIM176270) is a rare genetic disorder with recognizable dysmorphic features and multisystemic consequences such as endocrine, neurocognitive... (Review)
Review
Prader-Willi syndrome (PWS, OMIM176270) is a rare genetic disorder with recognizable dysmorphic features and multisystemic consequences such as endocrine, neurocognitive and metabolic ones. Although most patients with Prader-Willi syndrome exhibit hypogonadotropic hypogonadism, there is variability regarding sexual maturation, with precocious puberty occurring in rare cases. Our aim is to elaborate a thorough review of Prader-Willi patients with central precocious puberty, in order to raise awareness of such cases and to enhance our knowledge regarding the diagnosis and prompt treatment of this particular PWS patients.
Topics: Humans; Prader-Willi Syndrome; Puberty, Precocious; Sexual Maturation; Hypogonadism; Knowledge
PubMed: 37251677
DOI: 10.3389/fendo.2023.1150323 -
Genetics in Medicine : Official Journal... Sep 2021Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with hypothalamic dysfunction due to deficiency of imprinted genes located on the 15q11-q13 chromosome....
PURPOSE
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with hypothalamic dysfunction due to deficiency of imprinted genes located on the 15q11-q13 chromosome. Among them, the SNORD116 gene appears critical for the expression of the PWS phenotype. We aimed to clarify the role of SNORD116 in cellular and animal models with regard to growth hormone therapy (GHT), the main approved treatment for PWS.
METHODS
We collected serum and induced pluripotent stem cells (iPSCs) from GH-treated PWS patients to differentiate into dopaminergic neurons, and in parallel used a Snord116 knockout mouse model. We analyzed the expression of factors potentially linked to GH responsiveness.
RESULTS
We found elevated levels of circulating IGFBP7 in naive PWS patients, with IGFBP7 levels normalizing under GHT. We found elevated IGFBP7 levels in the brains of Snord116 knockout mice and in iPSC-derived neurons from a SNORD116-deleted PWS patient. High circulating levels of IGFBP7 in PWS patients may result from both increased IGFBP7 expression and decreased IGFBP7 cleavage, by downregulation of the proconvertase PC1.
CONCLUSION
SNORD116 deletion affects IGFBP7 levels, while IGFBP7 decreases under GHT in PWS patients. Modulation of the IGFBP7 level, which interacts with IGF1, has implications in the pathophysiology and management of PWS under GHT.
Topics: Animals; Growth Hormone; Humans; Induced Pluripotent Stem Cells; Mice; Neurons; Prader-Willi Syndrome; RNA, Small Nucleolar
PubMed: 34040195
DOI: 10.1038/s41436-021-01185-y -
Frontiers in Endocrinology 2023Oxytocin and vasopressin systems are altered in Prader Willi syndrome (PWS). However, investigations into endogenous oxytocin and vasopressin levels as well as clinical...
BACKGROUND
Oxytocin and vasopressin systems are altered in Prader Willi syndrome (PWS). However, investigations into endogenous oxytocin and vasopressin levels as well as clinical trials evaluating the effect of exogenous oxytocin on PWS symptoms have had mixed results. It is also unknown whether endogenous oxytocin and vasopressin levels are associated with certain PWS behaviours.
METHOD
We compared plasma oxytocin and vasopressin and saliva oxytocin levels in 30 adolescents and adults with PWS to 30 typically developing age-matched controls. We also compared neuropeptide levels between gender and genetic subtypes within the PWS cohort and examined the relationship between neuropeptide levels and PWS behaviours.
RESULTS
While we did not measure a group difference in plasma or saliva oxytocin levels, plasma vasopressin was significantly lower in individuals with PWS compared to controls. Within the PWS cohort, saliva oxytocin levels were higher in females compared to males and individuals with the mUPD compared to the deletion genetic subtype. We also found the neuropeptides correlated with different PWS behaviours for males and females and for genetic subtypes. For the deletion group, higher plasma and saliva oxytocin levels were related to fewer behaviour problems. For the mUPD group, higher plasma vasopressin levels were related to more behaviour problems.
CONCLUSION
These findings support existing evidence of a vasopressin system defect in PWS and for the first time identify potential differences in the oxytocin and vasopressin systems across PWS genetic subtypes.
Topics: Female; Male; Humans; Prader-Willi Syndrome; Oxytocin; Vasopressins; Phenotype; Plasma
PubMed: 37313445
DOI: 10.3389/fendo.2023.1183525 -
Genes Jan 2020Prader-Willi syndrome (PWS) is an imprinting disorder caused by lack of expression of the paternally inherited 15q11.2-q13 chromosome region. The risk of death from...
Prader-Willi syndrome (PWS) is an imprinting disorder caused by lack of expression of the paternally inherited 15q11.2-q13 chromosome region. The risk of death from obesity-related complications can worsen with age, but survival trends are improving. Comorbidities and their complications such as thrombosis or blood clots and venous thromboembolism (VTE) are uncommon but reported in PWS. Two phases of analyses were conducted in our study: unadjusted and adjusted frequency with odds ratios and a regression analysis of risk factors. Individuals with PWS or non-PWS controls with exogenous obesity were identified by specific International Classification of Diseases (ICD)-9 diagnostic codes reported on more than one occasion to confirm the diagnosis of PWS or exogenous obesity in available national health claims insurance datasets. The overall average age or average age per age interval (0-17yr, 18-64yr, and 65yr+) and gender distribution in each population were similar in 3136 patients with PWS and 3945 non-PWS controls for comparison purposes, with exogenous obesity identified from two insurance health claims dataset sources (i.e., commercial and Medicare advantage or Medicaid). For example, 65.1% of the 3136 patients with PWS were less than 18 years old (subadults), 33.2% were 18-64 years old (adults), and 1.7% were 65 years or older. After adjusting for comorbidities that were identified with diagnostic codes, we found that commercially insured PWS individuals across all age cohorts were 2.55 times more likely to experience pulmonary embolism (PE) or deep vein thrombosis (DVT) than for obese controls (-value: 0.013; confidence interval (CI) :1.22-5.32). Medi caid-insured individuals across all age cohorts with PWS were 0.85 times more likely to experience PE or DVT than obese controls (-value: 0.60; CI: 0.46-1.56), with no indicated age difference. Age and gender were statistically significant predictors of VTEs, and they were independent of insurance coverage. There was an increase in occurrence of thrombotic events across all age cohorts within the PWS patient population when compared with their obese counterparts, regardless of insurance type.
Topics: Age Distribution; Age Factors; Comorbidity; Female; Humans; Insurance, Health; Male; Medicaid; Medicare; Obesity; Odds Ratio; Prader-Willi Syndrome; Risk Factors; Thrombosis; United States; Venous Thromboembolism
PubMed: 31936105
DOI: 10.3390/genes11010067 -
Surgery For Obesity and Related... Aug 2023Obesity is the leading cause of morbidity and mortality in patients with Prader-Willi Syndrome (PWS). Our objective was to compare changes in body mass index (BMI) after... (Meta-Analysis)
Meta-Analysis
Obesity is the leading cause of morbidity and mortality in patients with Prader-Willi Syndrome (PWS). Our objective was to compare changes in body mass index (BMI) after metabolic and bariatric surgery (MBS) for the treatment of obesity (BMI ≥35 kg/m) in PWS. A systematic review of MBS in PWS was performed using PubMed, Embase, and Cochrane Central, identifying 254 citations. Sixty-seven patients from 22 articles met criteria for inclusion in the meta-analysis. Patients were organized into 3 groups: laparoscopic sleeve gastrectomy (LSG), gastric bypass (GB), and biliopancreatic diversion (BPD). No mortality within 1 year was reported in any of the 3 groups after a primary MBS operation. All groups experienced a significant decrease in BMI at 1 year with a mean reduction in BMI of 14.7 kg/m (P < .001). The LSG groups (n = 26) showed significant change from baseline in years 1, 2, and 3 (P value at year 3 = .002) but did not show significance in years 5, 7, and 10. The GB group (n = 10) showed a significant reduction in BMI of 12.1 kg/m in the first 2 years (P = .001). The BPD group (n = 28) had a significant reduction in BMI through 7 years with an average reduction of 10.7 kg/m (P = .02) at year 7. Individuals with PWS who underwent MBS had significant BMI reduction sustained in the LSG, GB, and BPD groups for 3, 2, and 7 years, respectively. No deaths within 1 year of these primary MBS operations were reported in this study or any other publication.
Topics: Humans; Bariatric Surgery; Biliopancreatic Diversion; Gastric Bypass; Obesity; Prader-Willi Syndrome; Body Mass Index
PubMed: 36872159
DOI: 10.1016/j.soard.2023.01.017 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Feb 2023
Topics: Humans; Prader-Willi Syndrome
PubMed: 36720608
DOI: 10.3760/cma.j.cn112140-20221126-01005 -
International Journal of Molecular... Feb 2021Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical... (Review)
Review
Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical manifestations are reported, such as short stature, cognitive and behavioral disability, temperature instability, hypotonia, hypersomnia, hyperphagia, and multiple endocrine abnormalities, including growth hormone deficiency and hypogonadism. The hypogonadism in PWS is due to central and peripheral mechanisms involving the hypothalamus-pituitary-gonadal axis. The early diagnosis and management of hypogonadism in PWS are both important for physicians in order to reach a better quality of life for these patients. The aim of this study is to summarize and investigate causes and possible therapies for hypogonadism in PWS. Additional studies are further needed to clarify the role of different genes related to hypogonadism and to establish a common and evidence-based therapy.
Topics: Chromosome Aberrations; Hormones; Humans; Hypogonadism; Prader-Willi Syndrome
PubMed: 33671467
DOI: 10.3390/ijms22041993 -
Revista Medica Del Instituto Mexicano... Jun 2021In this editorial the author presents a study, concerning Prader-Willi syndrome, which is paradigmatic for translational medicine, given that it creates a synergy...
In this editorial the author presents a study, concerning Prader-Willi syndrome, which is paradigmatic for translational medicine, given that it creates a synergy between genetics and molecular biology, in order to improve the care for patients suffering from this syndrome.
Topics: Angelman Syndrome; Epigenesis, Genetic; Humans; Prader-Willi Syndrome; Translational Research, Biomedical
PubMed: 34231979
DOI: No ID Found