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Value in Health : the Journal of the... Feb 2023To facilitate the development of new therapies for Prader-Willi syndrome (PWS), we sought to develop a reliable and valid assessment of anxiousness and distress, common...
OBJECTIVES
To facilitate the development of new therapies for Prader-Willi syndrome (PWS), we sought to develop a reliable and valid assessment of anxiousness and distress, common characteristics that have a significant negative impact on individuals with PWS and their families.
METHODS
The PWS Anxiousness and Distress Behaviors Questionnaire (PADQ) was developed with extensive input from clinical experts, as well as caregivers of individuals with PWS, who participated in iterative sets of qualitative interviews. The psychometric properties of the PADQ were subsequently demonstrated in a cross-sectional evaluation using data from the Global PWS Registry provided by > 400 caregivers and confirmed using data from a phase 3 clinical trial of an oxytocin analogue (intranasal carbetocin, LV-101).
RESULTS
Qualitative interview participants consistently endorsed the content of the PADQ and were confident they could accurately respond to each item based on their observations of their child's behavior. Analysis of cross-sectional data supported the computation of a total PADQ score, as well as the reliability and validity of the measure. The results of analyses using longitudinal clinical trial data confirmed these properties and provided evidence for the responsiveness of the PADQ, further supporting its appropriateness for the evaluation of new treatments targeting anxiousness and distress in PWS.
CONCLUSIONS
The current body of evidence supports the conclusion that the PADQ measures observable behaviors that are meaningful to patients and their families and provides a valid and reliable method to assess beneficial treatment effects for some of the most challenging behaviors associated with PWS.
Topics: Child; Humans; Prader-Willi Syndrome; Psychometrics; Reproducibility of Results; Cross-Sectional Studies; Anxiety; Surveys and Questionnaires
PubMed: 36202701
DOI: 10.1016/j.jval.2022.08.004 -
Tijdschrift Voor Psychiatrie 2021
Topics: Adult; Comorbidity; Human Growth Hormone; Humans; Prader-Willi Syndrome
PubMed: 34851524
DOI: No ID Found -
Canadian Respiratory Journal 2023Sleep-disordered breathing (SDB) is common in patients with Prader-Willi Syndrome (PWS). However, the prevalence of SDB varies widely between studies. Early...
INTRODUCTION
Sleep-disordered breathing (SDB) is common in patients with Prader-Willi Syndrome (PWS). However, the prevalence of SDB varies widely between studies. Early identification of SDB and factors contributing to its incidence is essential, particularly when considering growth hormone (GH) therapy.
OBJECTIVES
The aims of the study were to describe the prevalence and phenotypes of sleep-disordered breathing (SDB) in patients with Prader-Willi syndrome (PWS) and to determine the effects of age, gender, symptoms, GH therapy and body mass index on SDB severity.
METHODS
This study was a retrospective chart review of all patients with genetically confirmed Prader-Willi syndrome who underwent diagnostic overnight polysomnography (PSG) in the sleep laboratory at Sidra Medicine. Clinical and PSG data of enrolled patients were collected.
RESULTS
We identified 20 patients (nine males, eleven females) with PWS who had overnight sleep polysomnography (PSG) at a median age (IQR) of 5.83 (2.7-12) years. The median apnea-hypopnea index (AHI) was 8.55 (IQR 5.8-16.9) events/hour. The median REM-AHI was 27.8 (IQR 15-50.6) events/hour. The median obstructive apnea-hypopnea index (OAHI) was 7.29 (IQR 1.8-13.5) events/hour. The median central apnea-hypopnea index (CAHI) was 1.77 (IQR 0.6-4.1) events/hour. Nineteen patients (95%) demonstrated SDB by polysomnography (PSG) based on AHI ≥1.5 events/hour. Nine patients (45%) were diagnosed with obstructive sleep apnea (OSA). Three patients (15%) were diagnosed with central sleep apnea (CSA). Seven patients (35%) were diagnosed with mixed sleep apnea. No correlations were observed between AHI and age, gender, BMI, symptoms, or GH therapy. However, REM-AHI was significantly correlated with BMI (=0.031).
CONCLUSION
This study shows a high prevalence of SDB among our patients with PWS. Obstructive sleep apnea was the predominant phenotype. BMI was the only predictor for high REM-AHI. Further studies of large cohorts are warranted to define SDB in PWS and design the appropriate treatment.
Topics: Male; Female; Humans; Child, Preschool; Prader-Willi Syndrome; Retrospective Studies; Prevalence; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
PubMed: 37927914
DOI: 10.1155/2023/9992668 -
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 -
Endocrine Reviews Jan 2022Prader-Willi syndrome (PWS) is a rare genetic syndrome, caused by the loss of expression of the paternal chromosome 15q11-q13 region. Over the past years, many cases of... (Review)
Review
Prader-Willi syndrome (PWS) is a rare genetic syndrome, caused by the loss of expression of the paternal chromosome 15q11-q13 region. Over the past years, many cases of patients with characteristics similar to PWS, but without a typical genetic aberration of the 15q11-q13 region, have been described. These patients are often labelled as Prader-Willi-like (PWL). PWL is an as-yet poorly defined syndrome, potentially affecting a significant number of children and adults. In the current clinical practice, patients labelled as PWL are mostly left without treatment options. Considering the similarities with PWS, children with PWL might benefit from the same care and treatment as children with PWS. This review gives more insight into the pheno- and genotype of PWL and includes 86 papers, containing 368 cases of patients with a PWL phenotype. We describe mutations and aberrations for consideration when suspicion of PWS remains after negative testing. The most common genetic diagnoses were Temple syndrome (formerly known as maternal uniparental disomy 14), Schaaf-Yang syndrome (truncating mutation in the MAGEL2 gene), 1p36 deletion, 2p deletion, 6q deletion, 6q duplication, 15q deletion, 15q duplication, 19p deletion, fragile X syndrome, and Xq duplication. We found that the most prevalent symptoms in the entire group were developmental delay/intellectual disability (76%), speech problems (64%), overweight/obesity (57%), hypotonia (56%), and psychobehavioral problems (53%). In addition, we propose a diagnostic approach to patients with a PWL phenotype for (pediatric) endocrinologists. PWL comprises a complex and diverse group of patients, which calls for multidisciplinary care with an individualized approach.
Topics: Child; Genotype; Humans; Intellectual Disability; Muscle Hypotonia; Phenotype; Prader-Willi Syndrome; Proteins
PubMed: 34460908
DOI: 10.1210/endrev/bnab026 -
Frontiers in Endocrinology 2023Prader-Willi syndrome (PWS) is a rare, complex, genetic disorder characterized by hyperphagia, hypotonia, delayed psychomotor development, low muscle mass and...
BACKGROUND
Prader-Willi syndrome (PWS) is a rare, complex, genetic disorder characterized by hyperphagia, hypotonia, delayed psychomotor development, low muscle mass and hypothalamic dysfunction. Adults with PWS often have obesity, hypertension and type 2 diabetes mellitus (DM2), known risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Early symptoms of CVD and CKD may be masked by intellectual disability and inability to express physical complaints. Furthermore, kidney diseases are often asymptomatic. Therefore, renal and cardiovascular disease might be missed in patients with PWS. Microalbuminuria is an early sign of microvascular damage in the kidneys and other vascular beds. Therefore, we screened our adult PWS cohort for the presence of elevated urinary albumin and (micro)albuminuria.
METHODS
We retrospectively collected anthropometric measurements, blood pressure, medical history, medication use, urine dipstick and biochemical measurements form electronic patient files. In addition, we performed a systematic literature review on kidney disease in PWS.
RESULTS
We included 162 adults with genetically confirmed PWS (56% male, median age 28 years), of whom 44 (27%) had DM2. None had known CVD. All subjects had normal estimated glomerular filtration rate (eGFR) according to non-PWS reference intervals. Elevated urinary albumin or (micro)albuminuria was present in 28 (18%); 19 out of 75 (25%) had an increased urinary albumin-to-creatinine ratio (UACR) and 10 out of 57 (18%) had an increased urinary protein-to-creatinine ratio. Elevated urinary albumin was present at a young age (median age 26 (IQR 24-32) years) and was associated with an significantly higher BMI and LDL-cholesterol levels and higher prevalence of DM2, hypertension and dyslipidemia than those with normal UACR (=0.027, =0.019, <0.001, <0.001, =0.011 and respectively).
CONCLUSION
Upon screening, one in every five adults with PWS had increased urinary albumin or (micro)albuminuria, early signs of microvascular disease. All had normal eGFR, according to non-PWS reference intervals, and none had a formal diagnosis of CVD. As muscle mass is low in PWS, creatinine levels and eGFR may be spuriously normal. Urinalysis in this patient group can be used as a screening tool for microvascular (kidney) disease. We propose an algorithm for the detection and management of microvascular disease in adults with PWS.
Topics: Humans; Adult; Male; Young Adult; Female; Cohort Studies; Prader-Willi Syndrome; Diabetes Mellitus, Type 2; Retrospective Studies; Creatinine; Albuminuria; Hypertension; Cardiovascular Diseases; Renal Insufficiency, Chronic; Albumins
PubMed: 37547314
DOI: 10.3389/fendo.2023.1168648 -
Journal of Human Nutrition and... Oct 2021The management of Prader-Willi Syndrome (PWS) requires strict dietary supervision to prevent obesity, avoid micronutrient deficiencies and ensure optimal growth. The...
BACKGROUND
The management of Prader-Willi Syndrome (PWS) requires strict dietary supervision to prevent obesity, avoid micronutrient deficiencies and ensure optimal growth. The present study aimed to examine the growth and dietary intake of children with PWS.
METHODS
All children with genetically confirmed PWS attending Children's Health Ireland (CHI) at Tallaght (n = 44) were invited to participate. Anthropometry was performed and body composition measured using bioelectrical impedance analysis. Three-day food diaries were used to evaluate dietary intake and the presence of early feeding issues was assessed. Serum haemoglobin, ferritin and vitamin D levels were measured.
RESULTS
Nineteen children participated, with a mean (range) age of 7.6 (0.6-18.1) years. Most were female (n = 14, 74%). Twenty-percent (n = 3) were underweight, 60% (n = 9) were healthy weight, n = 1 was overweight and n = 2 were obese. Mean (range) percentage body fat was 25.7% (10%-40%). Eigthy-three percent reported early feeding issues. Ninety-four percent (n = 16) achieved ≤ 100% of estimated average requirement (EAR) for energy. Mean daily energy intake for ≤ 5 years old was 722 kcal (9 kcal cm /72-112% EAR); for those ≥ 12 years, it was 1203 kcal (8.3 kcal cm /41%-82% EAR). Suboptimal calcium, vitamin D, iron, zinc and fibre intake was evident. Iron deficiency anaemia and vitamin D insufficiency occurred in two children.
CONCLUSIONS
The present study provides the first Irish data for PWS and shows that energy intake does not appear to be excessive, with four in five patients being underweight or of a normal BMI. Suboptimal dietary intake of several micronutrients was evident and biochemical nutrient deficiencies were present.
Topics: Adolescent; Child; Child, Preschool; Eating; Energy Intake; Female; Humans; Iron Deficiencies; Micronutrients; Prader-Willi Syndrome
PubMed: 33835604
DOI: 10.1111/jhn.12882 -
International Journal of Molecular... Oct 2022This article reviews what we know of the phenotype and genotype of Prader-Willi syndrome and hypothesizes two possible paths from phenotype to genotype. It then suggests... (Review)
Review
This article reviews what we know of the phenotype and genotype of Prader-Willi syndrome and hypothesizes two possible paths from phenotype to genotype. It then suggests research that may strengthen the case for one or other of these hypotheses.
Topics: Humans; Prader-Willi Syndrome; Phenotype; Genotype
PubMed: 36292940
DOI: 10.3390/ijms232012089 -
Diabetes & Metabolic Syndrome Feb 2023Prader-Willi Syndrome (PWS) is a rare genetic disease. Oxytocin is a neuropeptide hormone that impacts fear, and social recognition. Intranasal administration of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Prader-Willi Syndrome (PWS) is a rare genetic disease. Oxytocin is a neuropeptide hormone that impacts fear, and social recognition. Intranasal administration of oxytocin can be utilized to treat PWS patients. The results of published trials assessing the effects of intranasal oxytocin in PWS are variable. The current systematic review aims to investigate the efficacy of oxytocin in Prader-Willi patients.
METHODS
We conducted a systematic literature search on Pubmed, Web of Science, and Scopus from inception to March 2022 for relevant interventional randomized controlled trials (RCTs) reporting the effect of oxytocin in patients with Prader-Willi syndrome. We assessed the quality of included trials using the Cochrane tool risk of bias 1. We performed the meta-analysis with Revman software version 5.4. In addition, we visualized our results using forest plots. We assessed the heterogeneity by using the Chi-square test.
RESULTS
Relevant to hyperphagia, the data extracted in three studies comprising 92 patients did not show positive outcomes of oxytocin compared to placebo (MD = 0.18; 95% CI: -0.44, 0.80; P = 0.56). Three studies that included 94 patients revealed no significant effects regarding weight between oxytocin and placebo (MD = 0.30; 95% CI: -0.22, 0.83; P = 0.25). The Aberrant Behaviour Checklist found that group-administered oxytocin improved behaviour compared to their counterpart who received a placebo.
CONCLUSION
Oxytocin didn't have significant effects on hyperphagia or weight. To establish the impact of oxytocin in Prader-Willi patients, additional prospective, large-sample randomized controlled trials (RCTs) are needed to avoid controversy.
Topics: Humans; Oxytocin; Prader-Willi Syndrome; Administration, Intranasal; Hyperphagia
PubMed: 36774885
DOI: 10.1016/j.dsx.2023.102711 -
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