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Orphanet Journal of Rare Diseases Feb 2024Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental condition characterised by a range of debilitating and lifelong symptoms. The many physical and...
Body weight, behaviours of concern, and social contact in adults and adolescents with Prader-Willi syndrome in full-time care services: Findings from pooled international archival data.
BACKGROUND
Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental condition characterised by a range of debilitating and lifelong symptoms. The many physical and behavioural challenges that arise with adults with PWS often necessitate full-time (i.e., 24-hour) professional care support. However, despite the fact that many clinicians regard full-time PWS-specific care to represent best practice, relatively few studies have directly examined the benefits of such services. The purpose of this paper is to use archival data to investigate the impact of full-time care services on people with PWS, and to assemble a large statistical dataset on which robust analyses of improvements in weight, BMI, and behavioural outcomes can be based.
METHODS
Information collated by the International PWS Organisation (IPWSO), an international non-profit membership organisation supporting national PWS associations around the world, was combined into a single anonymised dataset for statistical analysis. Data were supplied by service-providers from several countries who provide full-time support to people with PWS. The dataset included details on the specific services provided, basic demographic information on service recipients, including weight, body mass index (BMI), and observational records relating to behaviours of concern (BOC; consisting of temper outbursts, skin-picking, egocentrism, inflexibility, and striving for dominance).
RESULTS
A total of 193 people with PWS (ranging in age from < 10 yrs to > 50 yrs; 93% of whom were > 18 yrs), residing in 11 services across 6 countries, were represented in the dataset. On average, people with PWS showed significant reductions in weight and BMI after joining a full-time care service, with improvements within one year of entering, which were cumulative over time and independent of age or initial weight at entry. Similar cumulative improvements over time were seen for BOC within one year and were unrelated to age or severity of BOC at entry. The degree to which services are specialised for residents with PWS appeared to confer particular benefits, with people living in PWS-exclusive services showing the greatest improvements in weight, BMI, and BOC. Reductions in BOC were associated with greater, rather than less, social contact, suggesting that these improvements were not achieved at the expense of broader freedoms, such as the opportunity to meet with families and friends.
CONCLUSIONS
We conclude that full-time care services have a high likelihood of enhancing the lives of people with PWS within one year with long-lasting benefits, especially if those services are exclusive and specialised around the particular needs of PWS.
Topics: Adolescent; Adult; Child; Humans; Body Weight; Mental Disorders; Prader-Willi Syndrome; Middle Aged
PubMed: 38326873
DOI: 10.1186/s13023-024-03035-x -
Frontiers in Endocrinology 2024[This corrects the article DOI: 10.3389/fendo.2023.1168648.].
[This corrects the article DOI: 10.3389/fendo.2023.1168648.].
PubMed: 38318297
DOI: 10.3389/fendo.2024.1357219 -
Investigative Ophthalmology & Visual... Feb 2024To reveal the clinical significance, pathological involvement and molecular mechanism of imprinted in Prader-Willi syndrome (IPW) in RPE anomalies that contribute to AMD.
PURPOSE
To reveal the clinical significance, pathological involvement and molecular mechanism of imprinted in Prader-Willi syndrome (IPW) in RPE anomalies that contribute to AMD.
METHODS
IPW expression under pathological conditions were detected by microarrays and qPCR assays. In vitro cultured fetal RPE cells were used to study the pathogenicity induced by IPW overexpression and to analyze its upstream and downstream regulatory networks.
RESULTS
We showed that IPW is upregulated in the macular RPE-choroid tissue of dry AMD patients and in fetal RPE cells under oxidative stress, inflammation and dedifferentiation. IPW overexpression in fetal RPE cells induced aberrant apical-basal polarization as shown by dysregulated polarized markers, disrupted tight and adherens junctions, and inhibited phagocytosis. IPW upregulation was also associated with RPE oxidative damages, as demonstrated by intracellular accumulation of reactive oxygen species, reduced cell proliferation, and accelerated cell apoptosis. Mechanically, N6-methyladenosine level of the IPW transcript regulated its stability with YTHDC1 as the reader. IPW mediated RPE features by suppressing MEG3 expression to sequester its inhibition on the AKT serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) pathway. We also noticed that the mTOR inhibitor rapamycin suppresses the AKT/mTOR pathway to alleviate the IPW-induced RPE anomalies.
CONCLUSIONS
We revealed that IPW overexpression in RPE induces aberrant apical-basal polarization and oxidative damages, thus contributing to AMD progression. We also annotated the upstream and downstream regulatory networks of IPW in RPE. Our findings shed new light on the molecular mechanisms of RPE dysfunctions, and indicate that IPW blockers may be a promising option to treat RPE abnormalities in AMD.
Topics: Humans; Retinal Pigment Epithelium; Prader-Willi Syndrome; Proto-Oncogene Proteins c-akt; Up-Regulation; Macular Degeneration; Oxidative Stress; TOR Serine-Threonine Kinases; Adenine
PubMed: 38315495
DOI: 10.1167/iovs.65.2.10 -
Qualitative Health Research Jan 2024Daily experiences of mothers caring for children with Prader-Willi syndrome (PWS) are largely unknown and unvoiced. Knowledge of PWS has generally focused on pathology...
Daily experiences of mothers caring for children with Prader-Willi syndrome (PWS) are largely unknown and unvoiced. Knowledge of PWS has generally focused on pathology of the disorder. This emphasis overlooks the challenging moments of everyday life caring for children with PWS. Storied accounts of mothers caring for children with PWS offer expanded narratives to medicalized descriptions of experience. An understanding of everyday challenges in managing physical and mental health issues of PWS including hyperphagia and anxiety may create shifts in social and clinical perspectives. This understanding could improve practices in health and social care for families with PWS. This narrative inquiry studied everyday experience using storied accounts. Participants were mothers caring for children aged 3-17 years with genetically confirmed PWS who were experiencing hyperphagia. Four participants were recruited, and each interviewed 8-12 times over 12 months. Field texts and narrative accounts were co-composed through a collaborative process of analysis. Engaging with participants' day-to-day experiences offered insights into their work of nurturing, caring, and contributing to the care of a child with PWS. Narrative threads focused on complexity and rarity and include the desire to be normal, how ordinary becomes extraordinary, isolation, behaviors and normative standards, and alternative stories of mothering. Recommendations for practice and policy include (a) challenges of mothering a child with complexity, (b) moving beyond functionality and impairment to participation and quality of life, (c) re-storying narratives and supports for families, and (d) engaging with mothers to determine care priorities.
PubMed: 38282344
DOI: 10.1177/10497323231225412 -
Medicine Jan 2024Prader-Willi syndrome (PWS) is a genetic disorder affecting multiple systems. Approximately one-quarter of PWS patients will develop diabetes. Given the uncontrolled...
RATIONALE
Prader-Willi syndrome (PWS) is a genetic disorder affecting multiple systems. Approximately one-quarter of PWS patients will develop diabetes. Given the uncontrolled hyperphagia and resultant severe obesity in these patients, their glycemic management poses a significant challenge.
CASE REPORT
We present the clinical profile of a male patient diagnosed with both PWS and diabetes. Previous administration of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor Canagliflozin resulted in improved glycemic control and weight management. But at the age of 25, the patient was hospitalized due to worsened glycemic control and the detection of ketonuria. After thorough examination and clinical observation, we discovered that the patient ketonuria was associated with enhanced lipid metabolism related to Canagliflozin. After excluding the risk of SGLT-2 inhibitor-induced euglycemic diabetic ketoacidosis, adjustments of the hypoglycemic regimen, building upon prior treatment, were recommended for the patient.
CONCLUSION
It is important to note that among patients with both PWS and diabetes, the utilization of SGLT-2 inhibitors can lead to the emergence of ketonuria due to increased lipolysis. Therefore, any decision to discontinue SGLT-2 inhibitors should undergo thorough evaluation.
Topics: Adult; Humans; Male; Canagliflozin; Diabetes Mellitus; Diabetic Ketoacidosis; Ketosis; Prader-Willi Syndrome; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38277514
DOI: 10.1097/MD.0000000000037096 -
Frontiers in Endocrinology 2023
Topics: Humans; Obesity; Prader-Willi Syndrome
PubMed: 38239989
DOI: 10.3389/fendo.2023.1349582 -
Taiwanese Journal of Obstetrics &... Jan 2024We present a prenatal diagnosis strategy of using Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) for the detection of maternal...
OBJECTIVE
We present a prenatal diagnosis strategy of using Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) for the detection of maternal uniparental disomy 15/trisomy 15 (UPD(15) mat/T15) mosaicism.
CASE REPORT
A 43-year-old woman underwent amniocentesis at 19 weeks of gestation due to a high risk of trisomy 15 (T15) as indicated by non-invasive prenatal testing (NIPT). Cytogenetic analysis revealed a karyotype of 46, XX of cultured amniocytes. Further analysis using copy number variation sequencing (CNV-seq) analysis showed 55 % T15 mosaicism. The second amniocentesis was performed and showed a karyotype of 46, XX and 26 % T15 mosaicism by interphase fluorescence in situ hybridization (FISH). MS-MLPA analysis of uncultured amniocytes showed that the copy number ratio of 15q11-13 ranged from 1.3 to 1.5, and the percentage of methylation was between 70 % and 100 %. MS-MLPA assay of cultured amniocytes showed a copy number ratio of 1 and a methylation percentage of 100 %. Therefore, this fetus was identified to be an UPD(15) mat/T15 mosaicism. The parents decided to terminate the pregnancy.
CONCLUSION
MS-MLPA can be used in combination with karyotype and CNV-seq for prenatal diagnosis of NIPT high-risk T15 to avoid missed diagnosis of UPD(15) mat/T15 mosaicism.
Topics: Pregnancy; Female; Humans; Adult; In Situ Hybridization, Fluorescence; Prader-Willi Syndrome; Multiplex Polymerase Chain Reaction; Trisomy; DNA Copy Number Variations; Prenatal Diagnosis; Amniocentesis; Mosaicism; Comparative Genomic Hybridization; Chromosomes, Human, Pair 15; Uniparental Disomy
PubMed: 38216276
DOI: 10.1016/j.tjog.2023.09.022 -
Annals of Translational Medicine Dec 2023
PubMed: 38213817
DOI: 10.21037/atm-23-1718 -
BMC Pediatrics Jan 2024Recombinant human growth hormone (rhGH) therapy is beneficial for children with Prader-Willi syndrome (PWS) in improving short stature and metabolism, but the effect of...
Evaluating the effect of recombinant human growth hormone treatment on sleep-related breathing disorders in toddlers with Prader-Willi syndrome: a one-year retrospective cohort study.
BACKGROUND
Recombinant human growth hormone (rhGH) therapy is beneficial for children with Prader-Willi syndrome (PWS) in improving short stature and metabolism, but the effect of early rhGH treatment on respiratory and sleep parameters for PWS children under three years old remains elusive. Thus, this study aimed to investigate the impact of rhGH treatment on sleep-related breathing disorders (SRBDs) for toddlers with PWS.
METHODS
A total of 17 age-matched PWS patients receiving rhGH treatment (rhGH group) and 17 control individuals not receiving rhGH treatment (non-rhGH group) were recruited for this study between October 2018 and January 2023. Data related to polysomnography-polygraphy (PSG) and serum levels of insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) were collected.
RESULTS
The mean age in the rhGH group was 20.76 ± 9.22 months, which was comparable to that of the non-rhGH group (25.23 ± 13.81 months). The demographic and anthropometric parameters were similar across the two groups after 52 weeks of treatment. Administration of rhGH to toddlers did not exert adverse effects on the obstructive apnea-hypopnea index (OAHI), central apnea index (CAI), oxygen desaturation index (ODI), mean percutaneous oxygen saturation (SpO), lowest SpO, duration when SpO is lower than 90%, or proportion of the patients with SpO lower than 90%. Furthermore, the increased IGF-1 z-score and IGFBP-3 level did not worsen SRBDs.
CONCLUSION
Treatment with rhGH for 52 weeks on young toddlers with PWS showed no deleterious effects on SRBDs. This shed more light on the importance of initiating rhGH therapy early in PWS patients.
Topics: Humans; Child, Preschool; Infant; Human Growth Hormone; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Prader-Willi Syndrome; Retrospective Studies; Sleep
PubMed: 38200464
DOI: 10.1186/s12887-023-04513-0 -
Journal of Medical Case Reports Dec 2023Prader-Willi syndrome is a complex multisystem disorder due to the absent expression of paternally active genes in the Prader-Willi syndrome-critical region on...
BACKGROUND
Prader-Willi syndrome is a complex multisystem disorder due to the absent expression of paternally active genes in the Prader-Willi syndrome-critical region on chromosome 15 (15q11.2-q13). The main clinical features are hyperphagia (which frequently results in early-onset obesity), hypogonadism, developmental delays, typical behaviors (such as obsessive-compulsive tendencies, tantrums, perseveration, insistence on sameness, and rigidity), and distinctive facial features. In infants, the most prominent findings are hypotonia and feeding difficulties.
CASE PRESENTATION
This paper highlights a case of a 14 year old male patient of an Ethiopian ethnicity with diagnosis of Prader-Willi syndrome, which is first report in Ethiopia. He presented with progressive excessive weight gain, insatiable appetite, clinical and laboratory features of hypogonadism, ophthalmological refractory error, and facial features of Prader-Willi syndrome, which was further confirmed by genetic analysis. He is currently on lifestyle intervention, testosterone replacement, and treatment for vitamin D deficiency.
CONCLUSION
Prader-Willi syndrome should be considered in a child who presents with progressive weight gain and other typical clinical features such as cognitive impairment, excessive insatiable eating, or hypothalamic hypogonadism. Early lifestyle intervention may help to reduce excessive weight gain. To our knowledge, this is the first case reported in Ethiopia.
Topics: Adolescent; Humans; Male; Cognitive Dysfunction; Ethiopia; Hypogonadism; Prader-Willi Syndrome; Weight Gain
PubMed: 38143282
DOI: 10.1186/s13256-023-04282-5