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Clinical Genetics Dec 2019Pathogenic MAGEL2 variants result in the phenotypes of Chitayat-Hall syndrome (CHS), Schaaf-Yang syndrome (SYS) and Prader-Willi syndrome (PWS). We present five patients...
Pathogenic MAGEL2 variants result in the phenotypes of Chitayat-Hall syndrome (CHS), Schaaf-Yang syndrome (SYS) and Prader-Willi syndrome (PWS). We present five patients with mutations in MAGEL2, including the first patient reported with a missense variant, adding to the limited literature. Further, we performed a systematic review of the CHS and SYS literature, assess the overlap between CHS, SYS and PWS, and analyze genotype-phenotype correlations among them. We conclude that there is neither a clinical nor etiological difference between CHS and SYS, and propose that the two syndromes simply be referred to as MAGEL2-related disorders.
Topics: Abnormalities, Multiple; Adult; Child, Preschool; Cluster Analysis; DNA Mutational Analysis; Female; Humans; Infant; Infant, Newborn; Male; Mutation; Proteins; Young Adult
PubMed: 31397880
DOI: 10.1111/cge.13620 -
Clinical Endocrinology May 2019The aim of this systematic review was to summarize evidence on the acute responses of individuals with Prader-Willi syndrome (PWS) to physical exercise, and on the...
OBJECTIVE
The aim of this systematic review was to summarize evidence on the acute responses of individuals with Prader-Willi syndrome (PWS) to physical exercise, and on the effectiveness of long-term exercise interventions to improve the clinical manifestations of this syndrome.
DESIGN/METHODS
Relevant articles were identified in the electronic databases PubMed, Medline, CINAHL and SPORTDiscus (from inception to December 2018). Twenty-two studies including a total of 356 patients with PWS met all inclusion criteria and were included in the review.
RESULTS
Patients with PWS present with a decreased physical performance and impaired cardiorespiratory (maximal oxygen consumption, heart rate recovery after exercise) and hormonal (growth hormone release) responses to exercise. Most long-term exercise interventions have proven to decrease body mass while improving physical performance. Some benefits have also been reported in biochemical (glucose homeostasis, lipid profile) and biomechanical (gait pattern) variables, although there is controversy regarding the effects on body composition. No exercise-related adverse events have been reported in patients with PWS.
CONCLUSION
Physical exercise seems to be safe and effective for improving several phenotypes in PWS, notably physical fitness. However, further research is needed to confirm these results and especially to corroborate whether exercise per se or combined with dietary intervention is an effective coadjuvant treatment for reducing body mass in these patients.
Topics: Exercise Therapy; Humans; Outcome Assessment, Health Care; Prader-Willi Syndrome
PubMed: 30788853
DOI: 10.1111/cen.13953 -
World Journal of Pediatrics : WJP Feb 2019Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells....
BACKGROUND
Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells. This equilibrium is regulated by numerous cytokines, but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis, respectively. The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1). RANKL, sclerostin and DKKs-1 are often up-regulated in bone diseases, and they are the target of new monoclonal antibodies.
DATA SOURCES
The authors performed a systematic literature search in PubMed and EMBASE to June 2018, reviewed and selected articles, based on pre-determined selection criteria.
RESULTS
We re-evaluated the role of RANKL, osteoprotegerin, sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases, such as type 1 diabetes mellitus (T1DM), alkaptonuria (AKU), hemophilia A, osteogenesis imperfecta (OI), 21-hydroxylase deficiency (21OH-D) and Prader-Willi syndrome (PWS). To do so, we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-ß-catenin signaling pathways have been investigated, and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.
CONCLUSIONS
The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases. Furthermore, for some of them, bone damage began in childhood but only manifested with age. The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children, although further studies need to be carried out.
Topics: Adrenal Hyperplasia, Congenital; Alkaptonuria; Biomarkers; Bone Remodeling; Bone Resorption; Child; Diabetes Mellitus, Type 1; Hemophilia A; Humans; Intercellular Signaling Peptides and Proteins; Osteogenesis Imperfecta; Osteoprotegerin; Prader-Willi Syndrome; RANK Ligand; Up-Regulation; Wnt Signaling Pathway
PubMed: 30343446
DOI: 10.1007/s12519-018-0198-7 -
Journal of Assisted Reproduction and... Jun 2018To determine whether a history of conception by assisted reproductive technology (ART) is associated with occurrence of one or more imprinting disorders of either... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To determine whether a history of conception by assisted reproductive technology (ART) is associated with occurrence of one or more imprinting disorders of either maternal or paternal origin.
METHODS
We implemented a systematic review of scholarly literature followed by comprehensive meta-analysis to quantitatively synthesize data from reports relating to use of ART to occurrence of any imprinting disorder of humans, including Beckwith-Wiedemann (BWS), Angelman (AS), Prader-Willi (PWS), and Silver-Russell (SRS) syndromes, as well as transient neonatal diabetes mellitus (TNDB) and sporadic retinoblasoma (RB).
RESULTS
The systematic review identified 13 reports presenting unique data from 23 studies that related conception following ART to occurrence of imprinting disorders. Multiple studies of four disorder were identified, for which meta-analysis yielded the following summary estimates of associations with a history of ART: AS, summary odds ratio (sOR) = 4.7 (95% confidence interval (CI) 2.6-8.5, 4 studies); BWS, sOR = 5.8 (95% CI 3.1-11.1, 8 studies); PWS, sOR = 2.2 (95% CI 1.6-3.0, 6 studies); SRS, sOR = 11.3 (95% CI 4.5-28.5, 3 studies). Only one study reported on each of TNDB and RB.
CONCLUSION
Published data reveal positive associations between history of ART conception and each of four imprinting disorders. Reasons for these associations warrant further investigation.
Topics: Chromosome Disorders; Female; Fertilization; Genomic Imprinting; Humans; Reproductive Techniques, Assisted; Risk Factors
PubMed: 29696471
DOI: 10.1007/s10815-018-1173-x -
Advances in Nutrition (Bethesda, Md.) Nov 2017Prader-Willi syndrome (PWS) is a rare genetic disorder associated with excessive weight gain. Hyperphagia associated with PWS may result in higher energy intake, but... (Review)
Review
Prader-Willi syndrome (PWS) is a rare genetic disorder associated with excessive weight gain. Hyperphagia associated with PWS may result in higher energy intake, but alterations in energy expenditure may also contribute to energy imbalance. The purpose of this critical literature review is to determine the presence of alterations in energy expenditure in individuals with PWS. Ten studies that measured total energy expenditure (TEE), resting energy expenditure (REE), sleep energy expenditure (SEE), activity energy expenditure (AEE), and diet induced thermogenesis (DIT) were included in this review. The studies provided evidence that absolute TEE, REE, SEE, and AEE are lower in individuals with PWS than in age-, sex-, and body mass index-matched individuals without the syndrome. Alterations in lean body mass and lower physical activity amounts appear to be responsible for the lower energy expenditure in PWS rather than metabolic differences. Regardless of the underlying mechanism for lower TEE, the estimation of energy requirements with the use of equations derived for the general population would result in weight gain in individuals with PWS. The determination of energy requirements for weight management in individuals with PWS requires a more comprehensive understanding of energy metabolism. Future studies should aim to comprehensively profile all specific components of energy expenditure in individuals with PWS with the use of appropriately matched controls and gold standard methods to measure energy metabolism and body composition. One component of energy expenditure that is yet to be explored in detail in PWS is DIT. A reduced DIT (despite differences in fat free mass), secondary to hormonal dysregulation, may be present in PWS individuals, leading to a reduced overall energy expenditure. Further research exploring DIT in PWS needs to be conducted. Dietary energy recommendations for weight management in PWS have not yet been clearly established.
Topics: Body Mass Index; Diet; Energy Intake; Energy Metabolism; Humans; Prader-Willi Syndrome; Rest; Thermogenesis
PubMed: 29141973
DOI: 10.3945/an.117.016253 -
Journal of Intellectual Disabilities :... Mar 2019In Florida, the Agency for Persons with Disabilities provides waivers for adults with the following types of disabilities: intellectual disability, autism spectrum...
In Florida, the Agency for Persons with Disabilities provides waivers for adults with the following types of disabilities: intellectual disability, autism spectrum disorder, cerebral palsy, spina bifida, Down syndrome, and Prader-Willi syndrome. This review examined the peer-reviewed literature to indicate and assess the common needs for individuals with intellectual and developmental disabilities. Current models of service delivery, the efficacy of these services, and remaining gaps in the need fulfillment of individuals within the six diagnostic categorizations of interest were examined. Severity level within each diagnostic category was plotted on a matrix according to whether the needs of individuals were minimal, moderate, severe, or universal. The study found that sexual health education, socialization, and adult-focused medical care are universal needs among the six conditions. The study indicates that health-care professionals must work toward addressing the many unmet needs in comprehensive life span care services for adult individuals with neurodevelopmental disorders.
Topics: Adult; Autism Spectrum Disorder; Cerebral Palsy; Delivery of Health Care; Developmental Disabilities; Humans; Intellectual Disability; Needs Assessment; Spinal Dysraphism
PubMed: 28847208
DOI: 10.1177/1744629517726209 -
Journal of Neural Transmission (Vienna,... Jan 2017Invasive and non-invasive vagus nerve stimulation (VNS) is a promising add-on treatment for treatment-refractory depression, but is also increasingly evaluated for its... (Review)
Review
Invasive and non-invasive vagus nerve stimulation (VNS) is a promising add-on treatment for treatment-refractory depression, but is also increasingly evaluated for its application in other psychiatric disorders, such as dementia, schizophrenia, somatoform disorder, and others. We performed a systematic review aiming to give a detailed overview of the available evidence of the efficacy of VNS for the treatment of psychiatric disorders. Data derived from animal models, experimental trials without health-related outcomes, case reports, single-session studies, and reviews were excluded. From 1292 publications, 33 records were included for further analyses: 25 focused on VNS as treatment of unipolar or bipolar major depressive disorder and one investigated the neurocognitive improvement after VNS in major depressive disorder. Seven focused on the improvement of cognitive function in Alzheimer´s disease, improvement of schizophrenia symptoms, treatment of obsessive compulsive disorder (OCD), panic disorder (PD) and post-traumatic stress disorder (PTSD), treatment resistant rapid-cycling bipolar disorder, treatment of fibromyalgia, and Prader-Willi syndrome. A total of 29 studies used invasive VNS, while four studies used non-invasive, transcutaneous VNS. Only 7 out of 33 studies investigated conditions other than affective disorders. The efficacy data of VNS in affective disorders is promising, whereas more in controlled and naturalistic studies are needed. In other conditions like schizophrenia, Alzheimer's disease, OCD, PD, PTSD, and fibromyalgia, either no effects or preliminary data on efficacy were reported. At this point, no final conclusion can be made regarding the efficacy of VNS to improve symptoms in psychiatric disorders other than in affective disorders.
Topics: Evidence-Based Medicine; Humans; Mental Disorders; Psychiatry; Vagus Nerve Stimulation
PubMed: 27848034
DOI: 10.1007/s00702-016-1642-2 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2016Rare diseases (RD) are those that present a lower prevalence than 5 cases per 10.000 population. The main objective of this review was to study the effect on oral health... (Review)
Review
BACKGROUND
Rare diseases (RD) are those that present a lower prevalence than 5 cases per 10.000 population. The main objective of this review was to study the effect on oral health in rare diseases, while the secondary objective of the study is theme upgrade.
MATERIAL AND METHODS
Comparative observational case-control studies were analysed and a systematic review was conducted in PubMed. Each rare disease listed on the statistical data record of the Health Portal of the Ministry of Equality, Health and Social Policies Board of Andalusia was associated with "oral health". The variables studied included dental, oral mucosa and occlusion alterations, oral pathologies (caries, periodontal disease) and other alterations (mouth breathing, parafunctional habits, etc). A bias analysis of the variable caries was conducted.
RESULTS
Six RD were selected through our inclusion and exclusion criteria (hypogammaglobulinemia, Rett syndrome, Marfan syndrome, Prader-Willi syndrome, cystic fibrosis and Cri du chat syndrome) in a total of 8 publications, of which four trials were classified as high risk of bias and one of them as medium risk. There were not trials with low risk of bias.
CONCLUSIONS
The main statistically significant differences found by Syndrome compared to a control group were in Hypogammaglobulinemia with a greater tendency to enamel hypoplasia and dry mouth. The Rett syndrome had, as well, a greater tendency to an anterior open bite, ogival palate, bruxism, mouth breathing and tongue thrusting. Prader-Willi syndrome had a tendency of dental erosion, and Cri du chat syndrome showed a higher association to Tannerella forsythia.
Topics: Bruxism; Cri-du-Chat Syndrome; Dental Caries; Humans; Oral Health; Rare Diseases
PubMed: 27475682
DOI: 10.4317/medoral.20972 -
European Journal of Pediatrics Jan 2016Prader-Willi syndrome (PWS) is a rare genetic syndrome. The phenotype includes moderate to intellectual disability, dysmorphia, obesity, and behavioral disturbances... (Review)
Review
UNLABELLED
Prader-Willi syndrome (PWS) is a rare genetic syndrome. The phenotype includes moderate to intellectual disability, dysmorphia, obesity, and behavioral disturbances (e.g., hetero and self-injurious behaviors, hyperphagia, psychosis). Psychotropic medications are widely prescribed in PWS for symptomatic control. We conducted a systematic review of published literature to examine psychotropic medications used in PWS. MEDLINE was searched to identify articles published between January 1967 and December 2014 using key words related to pharmacological treatments and PWS. Articles with original data were included based on a standardized four-step selection process. The identification of studies led to 241 records. All selected articles were evaluated for case descriptions (PWS and behavioral signs) and treatment (type, titration, efficiency, and side effects). Overall, 102 patients were included in these studies. Treatment involved risperidone (three reports, n = 11 patients), fluoxetine (five/n = 6), naltrexone (two/n = 2), topiramate (two/n = 16), fluvoxamine (one/n = 1), mazindol (one/n = 2), N-acetyl cysteine (one/n = 35), rimonabant (one/n = 15), and fenfluramine (one/n = 15).
CONCLUSION
We identified promising treatment effects with topiramate for self-injury and impulsive/aggressive behaviors, risperidone for psychotic symptoms associated with uniparental disomy (UPD), and N-acetyl cysteine for skin picking. The pharmacological approach of behavioral impairment in PWS has been poorly investigated to date. Further randomized controlled studies are warranted.
WHAT IS KNOWN
Behavioral disturbances in Prader-Willi syndrome including aggressive reactions, skin picking, and hyperphagia might be very difficult to manage. Antipsychotic drugs are widely prescribed, but weight gain and increased appetite are their major side effects.
WHAT IS NEW
Topiramate might be efficient for self-injury and impulsive/aggressive behaviors, N-acetyl cysteine is apromising treatment for skin picking and Antidepressants are indicated for OCD symptoms. Risperidone is indicated in case of psychotic symptoms mainly associated with uniparental disomy.
Topics: Adolescent; Child; Child, Preschool; Cystine; Fructose; Humans; Prader-Willi Syndrome; Psychotropic Drugs; Risperidone; Topiramate
PubMed: 26584571
DOI: 10.1007/s00431-015-2670-x -
American Journal of Medical Genetics.... Dec 2015Prader-Willi syndrome (PWS) is a rare genetic disorder that results from lack of expression of paternally-derived genes on chromosome 15q11-13; caused by a deletion... (Meta-Analysis)
Meta-Analysis Review
Prader-Willi syndrome (PWS) is a rare genetic disorder that results from lack of expression of paternally-derived genes on chromosome 15q11-13; caused by a deletion (DEL), uniparental disomy (UPD), or a rare imprinting center defect. PWS is associated with a distinct behavioral phenotype that in some respects overlaps with autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by restricted or repetitive behaviors (RRBs) and social-communication impairment. The goal of this review was to (i) review published literature investigating core ASD symptoms in PWS and (ii) provide a prevalence estimate of ASD in PWS. Two independent reviewers searched Medline, CINAHL, PsychINFO, Embase, and Web of Science to find studies that answered the research questions. Individuals with PWS demonstrate significant levels of RRBs and social-communication impairment, in some reports reaching similar levels to those of non-PWS ASD comparison groups. Individuals with UPD had more social-communication impairment than those with DEL. Of 786 PWS participants, 210 (26.7%) were reported as meeting criteria for ASD, either based on clinical diagnosis or by exceeding clinical cut-points on relevant ASD symptom measures. In studies that distinguished genetic subtypes, rates of ASD were higher in individuals with PWS with UPD (67 of 190; 35.3%) than those with DEL (47 of 254; 18.5%). Published data on the association of PWS and ASD to date are limited to sample means of 8 years of age and older. Further research is needed to identify early markers of ASD in PWS children, to support earlier diagnosis and intervention for this important comorbidity.
Topics: Autism Spectrum Disorder; Humans; Prader-Willi Syndrome; Sequence Deletion; Social Communication Disorder; Uniparental Disomy
PubMed: 26331980
DOI: 10.1002/ajmg.a.37286