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BMC Pediatrics Aug 2016Prader-Willi syndrome is a rare genetic abnormality that can be challenging to diagnose early, but for which early interventions improve prognosis.
BACKGROUND
Prader-Willi syndrome is a rare genetic abnormality that can be challenging to diagnose early, but for which early interventions improve prognosis.
METHODS
To improve understanding of Prader-Willi syndrome in neonates in Asia, we retrospectively analyzed the clinical records of 20 affected newborns diagnosed in the Department of Neonatology, Guangzhou Women and Children's Medical Center, Guangzhou, China from January 2007 to December 2014 and performed a review of the relevant literature.
RESULTS
Fourteen boys and six girls presented with hypotonia, poor responsiveness, feeding difficulty, and infrequent, weak crying. Different from western patients, the 20 Asian patients exhibited at least five of the following typical features: prominent forehead, narrow face, almond-shaped eyes, small mouth, downturned mouth, thin upper lip, and micromandible. All 14 boys had a small scrotum, including nine with cryptorchidism. Diagnoses were made with microarray comparative genomic hybridization. All 20 infants required feeding tubes. Fifteen received swallowing training immediately after admission; the period of continuous tube feeding for these patients ranged from 8 to 22 days (mean, 14 ± 5.3 days). For the five patients who did not receive swallowing training, the period of continuous tube feeding ranged from 15 to 35 days (mean, 18 ± 4.3 days). Comprehensive care measures included: giving parents detailed health education and basic information about this disease, teaching skills to promote feeding and prevent suffocation, increasing children's passive activity, providing nutrition management for normal development, and preventing excessive or inadequate nutrient intake.
CONCLUSIONS
Neonates with Prader-Willi syndrome in Asia have hypotonia, poor responsiveness, feeding difficulty, infrequent and weak crying, genital hypoplasia, and characteristic facial features. Recognition of the syndrome in neonates with confirmation by genetic testing is essential, because early diagnosis allows early intervention. Treatment measures including swallowing training can improve prognosis, prevent growth retardation and obesity, and elevate quality of life in individuals with Prader-Willi syndrome.
Topics: China; Diagnosis, Differential; Female; Humans; Infant, Newborn; Male; Prader-Willi Syndrome; Prognosis; Retrospective Studies
PubMed: 27506196
DOI: 10.1186/s12887-016-0662-2 -
Journal of Pediatric Ophthalmology and... 1999Prader-Willi syndrome (PWS) refers to a genetic disorder induced by an anomaly on chromosome 15 occurring with a frequency of one in 10,000 to 20,000. It is...
PURPOSE
Prader-Willi syndrome (PWS) refers to a genetic disorder induced by an anomaly on chromosome 15 occurring with a frequency of one in 10,000 to 20,000. It is characterized by a unique set of features including infantile hypotonia, obesity in childhood, small hands and feet, hypogonadism, and mental retardation. Reported here are the results of ophthalmic examinations of persons with PWS, together with results from controls comparable in age, percentage of body fat, and intelligence. These data bear on the hypothesis that the ocular anomalies in PWS are unique to this syndrome.
METHOD
A comprehensive investigation of PWS brought children and adults to Vanderbilt University for extended testing, which included an ophthalmic examination. Genetic analysis determined unequivocally the PWS diagnosis and identified subgroups-deletion and maternal disomy. A group of persons without PWS but generally comparable in age, body composition, and intelligence served as controls.
RESULTS
Significant differences between the deletion and disomy subgroups were not found for the clinical ophthalmic measures. The incidence of anomalies in the combined PWS was similar to those reported in previous studies. A similar pattern was present in the control group except for myopia and stereopsis. An effect of genetic subgroup, however, was observed for random element stereopsis with the maternal disomy group having a greater degree of impairment.
CONCLUSION
The overall similarity between the PWS and control groups on all measures except myopia and stereopsis suggest that many of the anomalies in PWS found in prior studies are due to factors inherent in a general dysfunctional population, rather than reflective of an ocular signature unique to PWS.
Topics: Adult; Depth Perception; Eye Abnormalities; Humans; Myopia; Perceptual Disorders; Prader-Willi Syndrome; Visual Acuity
PubMed: 11132665
DOI: 10.3928/0191-3913-19991101-08 -
Archives of Disease in Childhood Jan 1994
Review
Topics: Age Factors; Chromosomes, Human, Pair 15; Female; Gene Deletion; Humans; Male; Prader-Willi Syndrome
PubMed: 8110011
DOI: 10.1136/adc.70.1.58 -
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 -
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 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 -
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 -
Medecine Sciences : M/S Oct 2015Prader-Willi syndrome is a neurodevelopmental disorder caused by the lack of expression of imprinted genes of the chromosomal region 15q11-q12. Diagnosis can now be made... (Review)
Review
Prader-Willi syndrome is a neurodevelopmental disorder caused by the lack of expression of imprinted genes of the chromosomal region 15q11-q12. Diagnosis can now be made in the first months of life, allowing a precise description of the natural history of the disease. Of interest, nutritional phases appear to be more complex than those initially reported, starting with a severe hypotonia with deficit of suckling and failure to thrive in neonates, and subsequently switching to excessive weight gain with morbid obesity due to hyperphagia and deficit of satiety. The phenotype also includes endocrine dysfunction, intellectual disability, learning deficits, behavioural troubles with impaired social skills and psychiatric features. Multidisciplinary care has been strongly improved by the rare disease programme launched in France in 2004 and the Obesity programme in 2011 in link with the patient association. New therapeutic perspectives have arisen from knowledge of the pathophysiology of PWS.
Topics: Diagnosis, Differential; Disease Progression; France; Genetic Testing; Humans; Hypogonadism; Mental Disorders; Phenotype; Prader-Willi Syndrome
PubMed: 26481024
DOI: 10.1051/medsci/20153110011 -
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