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Sample records for prader-willi syndrome pws

  1. Prader-Willi Syndrome Association

    Science.gov (United States)

    ... everyone will be talking about. Join the many families and individuals that are part of the PWS community this year in Orlando, FL from November ... of autism spectrum disorders in children with Prader-Willi syndrome pwsa | Jun ...

  2. Cardiac evaluation in children with Prader-Willi syndrome.

    NARCIS (Netherlands)

    Marcus, K.A.; Alfen-van der Velden, J. van; Otten, B.J.; Weijers, G.; Yntema, H.G.; Korte, C.L. de; Kapusta, L.

    2012-01-01

    AIM: To assess cardiac anatomy and myocardial systolic function in children with Prader-Willi syndrome (PWS). METHODS: Physical examination, electrocardiographic (ECG) recordings and transthoracic echocardiograms including two-dimensional speckle tracking echocardiography (2DSTE) were performed and

  3. Klinefelter's syndrome and Prader-Willi syndrome: A rare combination

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Vries, B.B. van; Duffels, S.J.H.; Egger, J.I.M.; Noordam, C.; Tuinier, S.

    2007-01-01

    In this paper a review is presented of the rare combination of Klinefelter's syndrome and Prader-Willi syndrome (PWS) and a second case of this combination with a uniparental disomy (UPD) etiology of PWS is described. Patients outlined in all other 8 reports and the present case have a PWS

  4. Klinefelter's syndrome and Prader-Willi syndrome: a rare combination.

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Vries, B.B. van; Duffels, S.J.H.; Egger, J.I.M.; Noordam, C.; Tuinier, S.

    2007-01-01

    In this paper a review is presented of the rare combination of Klinefelter's syndrome and Prader-Willi syndrome (PWS) and a second case of this combination with a uniparental disomy (UPD) etiology of PWS is described. Patients outlined in all other 8 reports and the present case have a PWS

  5. Three Siblings with Prader-Willi Syndrome: Brief Review of Sleep and Prader-Willi Syndrome

    OpenAIRE

    Bingeliene, Arina; Shapiro, Colin M.; Chung, Sharon A.

    2015-01-01

    Prader-Willi syndrome (PWS) is a genetic disorder characterized by short stature, mental retardation, hypotonia, functionally deficient gonads, and uncontrolled appetite leading to extreme obesity at an early age. Patients with this condition require multidisciplinary medical care, which facilitates a significant improvement in quality of life. PWS is the first human disorder to be attributed to genomic imprinting. Prevalence varies in the literature, ranging from 1 in 8,000 in the Swedish po...

  6. Diagnosis in Prader-Willi syndrome.

    OpenAIRE

    Chu, C E; Cooke, A; Stephenson, J B; Tolmie, J L; Clarke, B; Parry-Jones, W L; Connor, J M; Donaldson, M D

    1994-01-01

    Thirty one patients with the putative diagnosis of Prader-Willi syndrome were reassessed clinically and by DNA analysis. Eleven patients were judged not to have Prader-Willi syndrome and 20 to have the condition. This was confirmed by DNA analysis in all but one case. The diagnosis of Prader-Willi syndrome, especially in early infancy, should be made with caution unless confirmed by molecular genetic studies.

  7. Urinary incontinence in persons with Prader-Willi Syndrome

    NARCIS (Netherlands)

    Gontard, A. von; Didden, H.C.M.; Sinnema, M.; Curfs, L.M.G.

    2010-01-01

    OBJECTIVE To assess and identify the frequency and type of urinary incontinence (UI), as well as associated symptoms in persons with Prader-Willi syndrome (PWS). PWS is characterized by mental retardation, short stature, obesity and hypogonadism. The behavioural phenotype includes eating problems,

  8. Prader-Willi Syndrome: Two Case Studies.

    Science.gov (United States)

    Bahling, Elizabeth F.

    1979-01-01

    Prader-Willi Syndrome, also called "the eating disease", is a low-incidence handicap which cannot be diagnosed in infancy. Most adults reported in the literature are institutionalized and profoundly retarded. A study of the diagnosis and intervention of two Prader-Willi Syndrome children is presented. (Author/JKS)

  9. Genetics Home Reference: Prader-Willi syndrome

    Science.gov (United States)

    ... caused by a phenomenon called genomic imprinting. Most cases of Prader-Willi syndrome (about 70 percent) occur when a segment of ... More about Mutations and Health Inheritance Pattern Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a ...

  10. Case report: severe asymptomatic hyponatremia in Prader-Willi Syndrome.

    Science.gov (United States)

    Landau, Daniel; Hirsch, Harry J; Gross-Tsur, Varda

    2016-02-18

    Prader-Willi syndrome is a complex neurogenetic, multisystem disorder. Despite the variable endocrine abnormalities and hypothalamic-pituitary axis dysfunction, hyponatremia has been reported in only a few PWS patients. In previously reported PWS individuals, hyponatremia was associated with abnormal fluid intake or during desmopressin treatment. We describe an infant with Prader-Willi syndrome who had severe, prolonged asymptomatic hyponatremia without a history of excessive fluid intake or desmopressin treatment. We compare the findings with those of the few other reported cases and describe, for the first time, results of a hypertonic saline infusion test and studies of adrenal cortical function. Hyponatremia should be suspected in children with Prader-Willi syndrome, especially in infants with severe failure to thrive. Further studies are needed to determine the pathophysiology of hyponatremia in this syndrome.

  11. Physical health problems in adults with Prader-Willi syndrome

    NARCIS (Netherlands)

    Sinnema, M.; Maaskant, M.A.; Schrojenstein Lantman-de Valk, H.M.J. van; Nieuwpoort, I.C. van; Drent, M.L.; Curfs, L.M.G.; Schrander-Stumpel, C.T.R.M.

    2011-01-01

    Prader-Willi syndrome (PWS) is a genetic disorder which is characterized by severe hypotonia and feeding problems in early infancy. In later childhood and adolescence, this is followed by hyperphagia and extreme obesity if the diet is not strictly controlled. Data on physical health problems in

  12. What Causes Prader-Willi Syndrome?

    Science.gov (United States)

    ... a fundamental role in regulating hunger and fullness. Maternal uniparental disomy (pronounced yoo-nuh-puh-REN-tl ... 2018). Prader-Willi syndrome and early-onset morbid obesity NIH rare disease consortium: A review of natural ...

  13. Three Siblings with Prader-Willi Syndrome: Brief Review of Sleep and Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Arina Bingeliene

    2015-01-01

    Full Text Available Prader-Willi syndrome (PWS is a genetic disorder characterized by short stature, mental retardation, hypotonia, functionally deficient gonads, and uncontrolled appetite leading to extreme obesity at an early age. Patients with this condition require multidisciplinary medical care, which facilitates a significant improvement in quality of life. PWS is the first human disorder to be attributed to genomic imprinting. Prevalence varies in the literature, ranging from 1 in 8,000 in the Swedish population to 1 in 54,000 in the United Kingdom. Rarely, the genetic mechanism responsible for Prader-Willi syndrome can be inherited. We report a highly unique case of three siblings who share this condition. This report describes a case of two brothers and one half sister with PWS. All three siblings have sleep-related complaints. The sister died at the age of 24 years in her sleep, with the cause of death reported as obstructive sleep apnea. The outcome was positive in both of the brothers’ cases as a result of professional medical care and specific tailored recommendations implemented by their mother. A review of the relevant literature vis-à-vis sleep and PWS is provided.

  14. Prader-Willi Syndrome

    Science.gov (United States)

    ... syndrome can be helpful in genetic counseling. Complications Obesity-related complications In addition to having constant hunger, ... with this disorder are unable to have children. Osteoporosis. Osteoporosis causes bones to become weak and brittle, ...

  15. Prader Willi Syndrome: A Family's Experience

    Directory of Open Access Journals (Sweden)

    Emma Walker

    2006-01-01

    Full Text Available Genetic research has offered, and continues to offer, a medical explanation of chromosomal disorders such as Down Syndrome and Asberger Syndrome and more recently the rare chromosomal disorder Prader Willi Syndrome. This research gives a pathogenic explanation of disorders which includes historical background, genetic defects and clinical features. This study set out to offer an insight into the effects of PWS on the child and his/her family. It also aimed to highlight what support systems are in place in the Co. Louth area of Ireland for individuals with PWS. Unfortunately, PWS is not curable at this time. Between 1995-2003 there were 39 diagnosed cases of PWS in Ireland, an average of 4.3 per year. On average there are four infants or children diagnosed in Ireland with PWS per year (Turner, 2004, National Centre for Medical Genetics. This study is an exploratory and descriptive case study. This case study drew on multiple sources of evidence to construct a valid and unique illustration of PWS. The primary source of data was derived from in-depth interviews with the parents of a 3-year-old girl who has PWS. She was diagnosed during the third week of life. The evidence of this study suggests that non-specialist medical staff are not generally familiar with PWS. Training in relation to diagnostic criteria for chromosomal disorders would be extremely beneficial to them and to familes that are affected by the syndrome. This study highlights the need for parents to be their own child's advocate in obtaining desired support services for their area. Support services in the North East region have been greatly increased due to the setting up of the North Eastern Health Board (now known as Health Service Executive, North East Region Early Intervention Services (EIS in 2000.

  16. "Hungry Eyes": Visual Processing of Food Images in Adults with Prader-Willi Syndrome

    Science.gov (United States)

    Key, A. P. F.; Dykens, E. M.

    2008-01-01

    Background: Prader-Willi syndrome (PWS) is a genetic disorder associated with intellectual disabilities, compulsivity, hyperphagia and increased risks of life-threatening obesity. Food preferences in people with PWS are well documented, but research has yet to focus on other properties of food in PWS, including composition and suitability for…

  17. A Characterization of Movement Skills in Obese Children with and without Prader-Willi Syndrome

    Science.gov (United States)

    Lam, Melanie Y.; Rubin, Daniela A.; Duran, Andrea T.; Chavoya, Frank A.; White, Elizabeth; Rose, Debra J.

    2016-01-01

    Purpose: The aim of this study was twofold: (a) to measure and compare motor proficiency in obese children with Prader-Willi syndrome (OB-PWS) to that in obese children without PWS (OB), and (b) to compare motor proficiency in OB-PWS and OB to normative data. Method: Motor proficiency was measured using the Bruininks-Oseretsky Test of Motor…

  18. Visual-Motor Integration in Children with Prader-Willi Syndrome

    Science.gov (United States)

    Lo, S. T.; Collin, P. J. L.; Hokken-Koelega, A. C. S.

    2015-01-01

    Background: Prader-Willi syndrome (PWS) is characterised by hypotonia, hypogonadism, short stature, obesity, behavioural problems, intellectual disability, and delay in language, social and motor development. There is very limited knowledge about visual-motor integration in children with PWS. Method: Seventy-three children with PWS aged 7-17 years…

  19. Pituitary-Adrenal Axis in Prader Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Olivia S. Edgar

    2016-01-01

    Full Text Available Purpose: Prader Willi syndrome (PWS is a rare genetic condition that has concurrent endocrinological insufficiencies. The presence of growth hormone deficiency has been well documented, but adrenal insufficiency (AI is not widely reported. A review was conducted to investigate its prevalence and relevance in PWS in both adults and children. Methodology: A literature review was performed with the search terms “Prader-Willi syndrome” and “adrenal insufficiency”. Results: The review found studies disagree on the prevalence and method of investigation of AI in PWS. Case studies demonstrate that patients with PWS are at risk of premature death, often secondary to respiratory infections. The possibility that this may be the result of the inability to mount an effective cortisol response has been studied, with some evidence confirming AI in PWS patients. Most reports agreed AI is present in PWS, however, Farholt et al. showed no HPA axis dysfunction in adults, suggesting that perhaps it is rare in adults, and children should be the focus of further studies. Conclusion: AI is present in some patients with PWS. Further research is required to ensure optimal treatment can be implemented and to prevent premature deaths related to adrenal insufficiency. Clinicians should have a low threshold for testing the adrenal axis and considering treatment for adrenal insufficiency in PWS patients.

  20. Psychiatric disorders and behavioral problems in children with Prader-Willi syndrome and the effects of growth hormone treatment

    NARCIS (Netherlands)

    S.T. Lo (Sinddie)

    2015-01-01

    markdownabstract__Abstract__ This thesis includes studies about developmental, behavioral and psychiatric characteristics in children with Prader-Willi syndrome (PWS). Endocrinologists Prader, Labhart, and Willi were the first describing the combination of neonatal hypotonia, short

  1. Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome

    NARCIS (Netherlands)

    A. Lukoshe (Akvile); Van Dijk, S.E. (Suzanne E.); G.E. van den Bosch (Gerbrich); A. van der Lugt (Aad); T.J.H. White (Tonya); A.C.S. Hokken-Koelega (Anita)

    2017-01-01

    textabstractBackground: Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional

  2. Causes of death in Prader-Willi syndrome: Prader-Willi Syndrome Association (USA) 40-year mortality survey.

    Science.gov (United States)

    Butler, Merlin G; Manzardo, Ann M; Heinemann, Janalee; Loker, Carolyn; Loker, James

    2017-06-01

    Prader-Willi syndrome (PWS) is a rare, complex, neurodevelopmental genetic disorder that is associated with hyperphagia and morbid obesity in humans and leads to a shortened life expectancy. This report summarizes the primary causes of death and evaluates mortality trends in a large cohort of individuals with PWS. The US Prader-Willi Syndrome Association (PWSA (USA)) syndrome-specific database of death reports was collected through a cursory bereavement program for PWSA (USA) families using a brief survey created in 1999. Causes of death were descriptively characterized and statistically examined using Cox proportional hazards. A total of 486 deaths were reported (263 males, 217 females, 6 unknown) between 1973 and 2015, with mean age of 29.5 ± 16 years (2 months-67 years); 70% occurred in adulthood. Respiratory failure was the most common cause, accounting for 31% of all deaths. Males were at increased risk for presumed hyperphagia-related accidents/injuries and cardiopulmonary factors compared to females. PWS maternal disomy 15 genetic subtype showed an increased risk of death from cardiopulmonary factors compared to the deletion subtype. These findings highlight the heightened vulnerability to obesity and hyperphagia-related mortality in PWS. Future research is needed to address critical vulnerabilities such as gender and genetic subtype in the cause of death in PWS.Genet Med advance online publication 17 November 2016.

  3. An obese young man with uncontrolled diabetes and insatiable hunger: Prader-Willi syndrome

    Directory of Open Access Journals (Sweden)

    Abilash Nair

    2013-01-01

    Full Text Available Prader-Willi syndrome (PWS is a rare cause of obesity. With the rising incidence of obesity, clinicians need to be aware of genetic causes of obesity and when to suspect them. A case of PWS, which was diagnosed in adulthood, has been discussed. This case is special because of lack of history of floppiness in infancy and predominance behavioral problems.

  4. High unacylated ghrelin levels support the concept of anorexia in infants with Prader-Willi syndrome

    NARCIS (Netherlands)

    V. Beauloye (Véronique); G. Diène; R.J. Kuppens (Renske); Zech, F. (Francis); Winandy, C. (Coralie); C. Molinas (Catherine); S. Faye; Kieffer, I. (Isabelle); Beckers, D. (Dominique); R. Nergårdh (Ricard); B.P. Hauffa (Berthold); Derycke, C. (Christine); P.J.D. Delhanty (Patric); A.C.S. Hokken-Koelega (Anita); M. Tauber (Maïthé)

    2016-01-01

    textabstractBackground: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with different nutritional phases from suckling deficit with failure to thrive to early onset of obesity. Hyperghrelinemia has been described in PWS long before the development of obesity. Ghrelin is

  5. Face Discrimination Skills in Prader-Willi Syndrome and Autism Spectrum Disorder

    Science.gov (United States)

    Feldman, Benjamin H.; Dimitropoulos, Anastasia

    2014-01-01

    Individuals with Prader-Willi Syndrome (PWS) are at risk for autism spectrum disorder (ASD), including socialization problems. The PWS chromosome 15q11-13 maternal uniparental disomy (mUPD) subtype displays greater ASD symptoms than the paternal deletion (DEL) subtype. Since interpreting faces leads to successful socialization, we compared face…

  6. Life Satisfaction among Mothers of Individuals with Prader-Willi Syndrome

    Science.gov (United States)

    Shivers, Carolyn M.; Leonczyk, Caroline L.; Dykens, Elisabeth M.

    2016-01-01

    Mothers of individuals with Prader-Willi syndrome (PWS) often experience numerous stressors, even when compared to mothers of children with other intellectual and developmental disabilities. Despite this, these mothers show great variability in self-reported life satisfaction. Using data from a longitudinal study of individuals with PWS and their…

  7. The Transition between the Phenotypes of Prader-Willi Syndrome during Infancy and Early Childhood

    Science.gov (United States)

    Butler, Jill V.; Whittington, Joyce E.; Holland, Anthony J.; McAllister, Catherine J.; Goldstone, Anthony P

    2010-01-01

    Aim: Prader-Willi syndrome (PWS) is a genetic disorder historically characterized by two phenotypic stages. The early phenotype in infants is associated with hypotonia, poor suck, and failure to thrive. In later childhood, PWS is associated with intellectual disability, hyperphagia, as well as growth and sex hormone deficiency. Little is known…

  8. Recognition of Emotion in Facial Expression by People with Prader-Willi Syndrome

    Science.gov (United States)

    Whittington, J.; Holland, T.

    2011-01-01

    Background: People with Prader-Willi syndrome (PWS) may have mild intellectual impairments but less is known about their social cognition. Most parents/carers report that people with PWS do not have normal peer relationships, although some have older or younger friends. Two specific aspects of social cognition are being able to recognise other…

  9. A Preliminary Analysis of the Phenomenology of Skin-Picking in Prader-Willi Syndrome

    Science.gov (United States)

    Morgan, Jessica R.; Storch, Eric A.; Woods, Douglas W.; Bodzin, Danielle; Lewin, Adam B.; Murphy, Tanya K.

    2010-01-01

    To examine the nature and psychosocial correlates of skin-picking behavior in youth with Prader-Willi Syndrome (PWS). Parents of 67 youth (aged 5-19 years) with PWS were recruited to complete an internet-based survey that included measures of: skin-picking behaviors, the automatic and/or focused nature of skin-picking, severity of skin-picking…

  10. Cognitive and Adaptive Advantages of Growth Hormone Treatment in Children with Prader-Willi Syndrome

    Science.gov (United States)

    Dykens, Elisabeth M.; Roof, Elizabeth; Hunt-Hawkins, Hailee

    2017-01-01

    Background: People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient…

  11. Students with Prader-Willi Syndrome: Case Law under the IDEA

    Science.gov (United States)

    Zirkel, Perry A.

    2017-01-01

    Prader-Willi Syndrome (PWS) is one of the low-incidence physical disabilities that the literature has not addressed in relation to the Individuals with Disabilities Education Act and its case law applications. To help fill the gap, this relatively brief article provides (a) an introduction of PWS from legal sources; (b) an overview of the IDEA,…

  12. Prader-Willi Syndrome, Management of Impulsivity, and Hyperphagia in an Adolescent.

    Science.gov (United States)

    Puri, M Rehan; Sahl, Robert; Ogden, Shawwna; Malik, Salma

    2016-05-01

    The aim of this article is to review related literature on management of hyperphagia and impulsive behaviors in Prader-Willi syndrome (PWS) that includes either naltrexone or bupropion. In this article we also discuss a case of a 13-year-old female with PWS struggling with some behavioral and psychiatric symptoms.

  13. Behavioural and Emotional Disturbances in People with Prader-Willi Syndrome

    Science.gov (United States)

    Steinhausen, H.-C.; Eiholzer, U.; Hauffa, B. P.; Malin, Z.

    2004-01-01

    The study of the behaviour profile in subjects with Prader-Willi Syndrome (PWS). A total of fifty-eight 3- to 29-year-old subjects with PWS were studied using a standardized parent report of behavioural and emotional disturbances. There was an increase of behavioural and emotional disturbances for the adolescent and young adult age range, whereas…

  14. Food addiction and cues in prader-willi syndrome.

    Science.gov (United States)

    von Deneen, Karen M; Gold, Mark S; Liu, Yijun

    2009-03-01

    Obesity research has recognized that there are many factors contributing to this devastating disorder. Much debate has arisen among scientists to develop models that might be useful in understanding why obesity has become a major health problem and epidemic. However, much of the current debate has been fractious and causes of obesity have been attributed solely to behavior or fast food, personality issues, depression, addiction, or genetics. One of the neurohormonal and genetic causes has been found in Prader-Willi syndrome (PWS), which results in excessive, pathologic reinforcement of food. We have studied PWS to delineate the neurobiology so that environmental cue stimulation may be explained for PWS. Neuroimaging studies have shown that appetizing food and food cues are associated with appetite stimulation. Appetite control is poor in PWS, thus food cues play a major role in its regulation. Hence, PWS may be the genetic model of choice for obesity.

  15. Growth Hormone Therapy in Adults with Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Karen S. Vogt

    2015-04-01

    Full Text Available Prader-Willi syndrome (PWS is characterized by hyperphagia, obesity if food intake is not strictly controlled, abnormal body composition with decreased lean body mass and increased fat mass, decreased basal metabolic rate, short stature, low muscle tone, cognitive disability, and hypogonadism. In addition to improvements in linear growth, the benefits of growth hormone therapy on body composition and motor function in children with PWS are well established. Evidence is now emerging on the benefits of growth hormone therapy in adults with PWS. This review summarizes the current literature on growth hormone status and the use of growth hormone therapy in adults with PWS. The benefits of growth hormone therapy on body composition, muscle strength, exercise capacity, certain measures of sleep-disordered breathing, metabolic parameters, quality of life, and cognition are covered in detail along with potential adverse effects and guidelines for initiating and monitoring therapy.

  16. Molecular characterization of a patient presumed to have prader-willi syndrome.

    Science.gov (United States)

    Falaleeva, Marina; Sulsona, Carlos R; Zielke, Horst R; Currey, Kathleen M; de la Grange, Pierre; Aslanzadeh, Vahid; Driscoll, Daniel J; Stamm, Stefan

    2013-01-01

    Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116. Currently, there are no mouse models that faithfully reflect the human phenotype and investigations rely on human post-mortem material. During molecular characterization of tissue deposited in a public brain bank from a patient diagnosed with Prader-Willi syndrome, we found RNA expression from SNRPN, SNORD115, and SNORD116 which does not support a genetic diagnosis of Prader-Willi syndrome. The patient was a female, Caucasian nursing home resident with history of morbid obesity (BMI 56.3) and mental retardation. She died at age of 56 from pulmonary embolism. SNORD115 and SNORD116 are unexpectedly stable in post mortem tissue and can be used for post-mortem diagnosis. Molecular characterization of PWS tissue donors can confirm the diagnosis and identify those patients that have been misdiagnosed.

  17. Physical health problems in adults with Prader-Willi syndrome.

    Science.gov (United States)

    Sinnema, Margje; Maaskant, Marian A; van Schrojenstein Lantman-de Valk, Henny M J; van Nieuwpoort, I Caroline; Drent, Madeleine L; Curfs, Leopold M G; Schrander-Stumpel, Constance T R M

    2011-09-01

    Prader-Willi syndrome (PWS) is a genetic disorder which is characterized by severe hypotonia and feeding problems in early infancy. In later childhood and adolescence, this is followed by hyperphagia and extreme obesity if the diet is not strictly controlled. Data on physical health problems in adults with PWS are scarce. We report on the prevalence of physical health problems in a Dutch cohort of adults with PWS in relation to age, BMI, and genetic subtype. Participants (n = 102) were retrieved via the Dutch Prader-Willi Parent Association and through physicians specializing in persons with intellectual disabilities (ID). Details regarding physical health problem spanning the participants' lifespan were collected from caretakers through semi-structured interviews. Cardiovascular problems included diabetes mellitus, hypertension, and cerebrovascular accidents. Respiratory infections were frequent in adulthood. In males, cryptorchidism was almost universal, for which 28/48 males had a history of surgery, mostly orchidopexy. None of the women had a regular menstrual cycle. Sixteen individuals had a diagnosis of osteoporosis. Spinal deformation, hip dysplasia, and foot abnormalities were common. Skinpicking, leg edema, and erysipelas were frequent dermatological problems. The findings in our group support the notion that the prevalence of physical health problems is underestimated. This underscores the importance of developing monitoring programs which would help to recognize physical health problems at an early stage. Copyright © 2011 Wiley-Liss, Inc.

  18. Testicular failure in boys with Prader-Willi syndrome: Longitudinal studies of reproductive hormones

    NARCIS (Netherlands)

    E.P.C. Siemensma (Elbrich); R.F.A. De Lind Van Wijngaarden (Roderick F.); B.J. Otten (Barto); F.H. de Jong (Frank); A.C.S. Hokken-Koelega (Anita)

    2012-01-01

    textabstractContext: The pathophysiology of hypogonadism in boys with Prader-Willi Syndrome( PWS) remains uncertain. Several reports described hypogonadotropic hypogonadism, some reported primary gonadal failure, and others a combination of both. Objectives: The aim of the study was to evaluate

  19. Testicular failure in boys with Prader-Willi syndrome: longitudinal studies of reproductive hormones.

    NARCIS (Netherlands)

    Siemensma, E.P.C.; Lind van Wijngaarden, R.F. de; Otten, B.J.; Jong, F.H. de; Hokken-Koelega, A.C.S.

    2012-01-01

    CONTEXT: The pathophysiology of hypogonadism in boys with Prader-Willi Syndrome (PWS) remains uncertain. Several reports described hypogonadotropic hypogonadism, some reported primary gonadal failure, and others a combination of both. OBJECTIVES: The aim of the study was to evaluate gonadal function

  20. The Relationship between Specific Cognitive Impairment and Behaviour in Prader-Willi Syndrome

    Science.gov (United States)

    Woodcock, K. A.; Oliver, C.; Humphreys, G. W.

    2011-01-01

    Background: Individuals with Prader-Willi syndrome (PWS) have been shown to demonstrate a particular cognitive deficit in attention switching and high levels of preference for routine and temper outbursts. This study assesses whether a specific pathway between a cognitive deficit and behaviour via environmental interaction can exist in individuals…

  1. The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome.

    NARCIS (Netherlands)

    Fronczek, R.; Lammers, G.J.; Balesar, R.; Unm, U.A.hopa; Swaab, D.F.

    2005-01-01

    CONTEXT: Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration of the hypocretin neurons. In addition to excessive daytime sleepiness, Prader-Willi syndrome (PWS) patients may show

  2. The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome

    NARCIS (Netherlands)

    Fronczek, Rolf; Lammers, Gert Jan; Balesar, Rawien; Unmehopa, Unga A.; Swaab, Dick F.

    2005-01-01

    Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration of the hypocretin neurons. In addition to excessive daytime sleepiness, Prader-Willi syndrome (PWS) patients may show narcolepsy-like

  3. The dilemma of diagnostic testing for Prader-Willi syndrome

    Science.gov (United States)

    Hung, Dorothy

    2017-01-01

    Although Prader-Willi syndrome (PWS) is a well-described clinical dysmorphic syndrome, DNA testing is required for a definitive diagnosis. A definitive diagnosis can be made in approximately 99% of cases using DNA testing; there are a number of DNA tests that can be used for this purpose, although there is no set standard algorithm of testing. The dilemma arises because of the complex genetic mechanisms at the basis of PWS, which need to be elucidated. To establish the molecular mechanism with a complete work up, involves at least 2 tests. Here we discuss the commonly used tests currently available and suggest a cost—effective approach to diagnostic testing. PMID:28164030

  4. The Need for Control/Comparison Studies in Establishing Diagnostic Indicators: Prader-Willi Syndrome as a Case in Point.

    Science.gov (United States)

    Taylor, Ronald L.; Caldwell, Mary Lou

    1990-01-01

    The psychometric characteristics of 12 adults with Prader-Willi syndrome (PWS) and a group without PWS but with other similar traits were compared. Results found cognitive, behavioral and educational traits often associated with PWS to be present in both groups, illustrating the importance of control/comparison groups in research establishing…

  5. Mechanisms of obesity in Prader-Willi syndrome.

    Science.gov (United States)

    Khan, M J; Gerasimidis, K; Edwards, C A; Shaikh, M G

    2018-01-01

    Obesity is the most common cause of metabolic complications and poor quality of life in Prader-Willi syndrome (PWS). Hyperphagia and obesity develop after an initial phase of poor feeding and failure to thrive. Several mechanisms for the aetiology of obesity in PWS are proposed, which include disruption in hypothalamic pathways of satiety control resulting in hyperphagia, aberration in hormones regulating food intake, reduced energy expenditure because of hypotonia and altered behaviour with features of autism spectrum disorder. Profound muscular hypotonia prevents PWS patients from becoming physically active, causing reduced muscle movements and hence reduced energy expenditure. In a quest for the aetiology of obesity, recent evidence has focused on several appetite-regulating hormones, growth hormone, thyroid hormones and plasma adipocytokines. However, despite advancement in understanding of the genetic basis of PWS, there are contradictory data on the role of satiety hormones in hyperphagia and data regarding dietary intake are limited. Mechanistic studies on the aetiology of obesity and its relationship with disease pathogenesis in PWS are required. . In this review, we focused on the available evidence regarding mechanisms of obesity and potential new areas that could be explored to help unravel obesity pathogenesis in PWS. © 2016 World Obesity Federation.

  6. Thoughts on the behavioural phenotypes in Prader-Willi syndrome and velo-cardio-facial syndrome: A novel approach

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Egger, J.I.M.; Tuinier, S.

    2007-01-01

    In both Prader-Willi syndrome (PWS) and 22q11 deletion syndrome [velo-cardio-facial syndrome (VCFS)], an increased risk for psychotic disorders is reported, which are as a rule not included in the behavioural phenotype of these two syndromes. For the description of a behavioural phenotype, the

  7. Polysomnography test and sleep disordered breathing in Prader-Willi syndrome

    Directory of Open Access Journals (Sweden)

    Andreea- Iulia Dobrescu1,

    2016-12-01

    Full Text Available INTRODUCTION Prader Willi syndrome (PWS is a rare condition and represents the most frequent cause of syndromic obesity. Sleep apnea is a life-threatening affection and is documented as the main cause of sudden death in PWS. OBJECTIVES AND BACKGROUND The aim of our study was to evaluate sleep disorders in PWS patients. MATERIALS AND METHODS We used a portable monitor that recorded time in bed (TIB, the air flow in the upper airways, oxygen saturation, heart rate and snoring. The included patients had a positive clinical and molecular diagnosis of PWS. RESULTS The mean of TIB was 439.3±117.19 minutes. We recorded obstructive, central and mixed apnea, hypopnea and short wakes caused by respiratory events that were variable number and duration, in all patients. cardiovascular morbidity and mortality and improved life quality. Moreover, small doses of these drugs proved to be effective even in patients where hemodialysis alone was enough to control blood pressure. CONCLUSIONS Sleep disorders are present in most PWS patients, not only obese ones according to their anatomical particularities. These events prevent the use of growth hormone therapy, the only available treatment that decreases the adipose mass and increase both prognosis and life quality in PWS patients. Graphical abstract: Polysomnography Test in a PWS patient. REFERENCES 1. Vandeleur M, Davey MJ, Nixon GM. Are sleep studies helpful in children with Prader-Willi syndrome prior to commencement of growth hormone therapy? J Paediatr Child Health. 2013;49:238–41. 2. Giordano L, Toma S, Palonta F, Teggi R, Zucconi M, Candia SD, et al. Obstructive sleep apnea in Prader-Willi syndrome: risks and advantages of adenotonsillectomy. Pediatr Med Chir. 2015;37(2. 3. Pavone M, Caldarelli V, Khirani S, Colella M, Ramirez A, Aubertin G, et al. Sleep disordered breathing in patients with Prader-Willi syndrome: A multicenter study. Pediatr Pulmonol. 2015;50:1354–9

  8. Blount disease in a case of Prader-Willi syndrome: why is it not as prevalent as in obesity without Prader-Willi syndrome?

    Science.gov (United States)

    Dulka, Susan; Choudhary, Arabinda Kumar; Methratta, Sosamma; Fortuna, Kristine

    2013-05-01

    Prader-Willi syndrome (PWS) is a genetic disorder causing multisystem abnormalities with obesity. Obesity is a well established cause of Blount disease. A 7-year-old girl with PWS presented with genu varum of the left knee with deformity of the proximal medial tibial condyle, which was consistent with Blount disease. A lateral physeal stapling and subsequent osteotomy for the left proximal tibia and fibula were performed with improved anatomical alignment. Blount disease has not been reported in the literature in association with PWS despite excessive obesity.

  9. The use of medical care and the prevalence of serious illness in an adult Prader-Willi syndrome cohort

    NARCIS (Netherlands)

    Sinnema, M.; Maaskant, M.A.; Schrojenstein Lantman-de Valk, H.M. van; Boer, H. de; Curfs, L.M.G.; Schrander-Stumpel, C.T.R.M.

    2013-01-01

    INTRODUCTION: Adults with Prader-Willi syndrome (PWS) have an increased occurrence of several medical conditions. We report on the consequences of high morbidity rates such as prevalence rate of hospital admissions, medication use and surgery in a Dutch cohort of adults with PWS. Special attention

  10. Gait Pattern in Two Rare Genetic Conditions Characterized by Muscular Hypotonia: Ehlers-Danlos and Prader-Willi Syndrome

    Science.gov (United States)

    Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

    2011-01-01

    This study aimed to quantify and compare the gait pattern in Ehlers-Danlos (EDS) and Prader-Willi syndrome (PWS) patients to provide data for developing evidence-based rehabilitation strategies. Twenty EDS and 19 PWS adult patients were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters…

  11. Randomized controlled trial to investigate the effects of growth hormone treatment on scoliosis in children with Prader-Willi syndrome.

    NARCIS (Netherlands)

    Lind van Wijngaarden, R.F. de; Klerk, L.W. de; Festen, D.A.M.; Duivenvoorden, H.J.; Otten, B.J.; Hokken-Koelega, A.C.S.

    2009-01-01

    CONTEXT: The prevalence of scoliosis in children with Prader-Willi syndrome (PWS) is 30-80%, depending on age. Although reports about effects of GH treatment on scoliosis in children with PWS are limited, scoliosis is generally considered a contraindication for GH treatment. OBJECTIVE: The aim was

  12. Psychomotor development in infants with Prader-Willi syndrome and associations with sleep-related breathing disorders.

    NARCIS (Netherlands)

    Festen, D.A.M.; Wevers, M.; Weerd, A.W. de; Bossche, R.A. van den; Duivenvoorden, H.J.; Otten, B.J.; Wit, J.M.; Hokken-Koelega, A.C.S.

    2007-01-01

    Prader-Willi syndrome (PWS) is a neurogenetic disorder with hypotonia, psychomotor delay, obesity, short stature, and sleep-related breathing disorders. The aim of this study was to evaluate the association between psychomotor development and sleep-related breathing disorders in PWS infants. Bayley

  13. Reduced cortical complexity in children with prader-willi syndrome and its association with cognitive impairment and developmental delay

    NARCIS (Netherlands)

    A. Lukoshe (Akvile); A.C.S. Hokken-Koelega (Anita); A. van der Lugt (Aad); T.J.H. White (Tonya)

    2014-01-01

    textabstractBackground: Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no

  14. Functional Assessment and Behavioral Treatment of Skin Picking in a Teenage Girl With Prader-Willi Syndrome

    NARCIS (Netherlands)

    Radstaake, M.; Didden, H.C.M.; Bolio, M.M.L.; Lang, R.B.; Lancioni, G.E.; Curfs, L.M.G.

    2011-01-01

    Skin picking is common in individuals with Prader-Willi Syndrome (PWS) but few treatment studies exist. This study reports the successful functional behavioral assessment (FBA) and treatment of skin picking in a 16-year-old female with PWS. A treatment package based on FBA results consisted of

  15. The GH/IGF-I axis and pituitary function and size in adults with Prader-Willi syndrome

    NARCIS (Netherlands)

    van Nieuwpoort, I.C.; Sinnema, M.; Castelijns, J.A.; Twisk, J.W.; Curfs, L.M.; Drent, M.L.

    2011-01-01

    Background: In adults with Prader-Willi syndrome (PWS), limited information is available about pituitary function, more specifically the prevalence of growth hormone deficiency (GHD). The aim of this study was to gain more insight into endocrine function in PWS adults, with emphasis on GH secretion.

  16. Subclinical dysphagia in persons with Prader-Willi syndrome.

    Science.gov (United States)

    Gross, Roxann Diez; Gisser, Ronit; Cherpes, Gregory; Hartman, Katie; Maheshwary, Rishi

    2017-02-01

    Prader-Willi Syndrome (PWS) is caused by a genetic imprinting abnormality resulting from the lack of expression of the paternal genes at 15q11-q13. Intellectual disability, low muscle tone, and life-threatening hyperphagia are hallmarks of the phenotype. The need for the Heimlich maneuver, death from choking, and pulmonary infection occur in a disproportionally high number of persons with PWS. The widely held belief is that eating behaviors are responsible for choking and aspiration; yet, no investigation had sought to determine if swallowing impairments were present in persons with PWS. To address this research and clinical gap, simultaneous videofluoroscopy and nasal respiratory signals were used to record swallowing function and breathing/swallowing coordination in 30 participants with PWS. Subjects consumed thin liquid and barium cookies under two randomized conditions as follows: (i) controlled (cues to swallow and standardized bolus sizes); (ii) spontaneous (no cues or bolus size control). Under videofluoroscopy, the cohort showed disordered pharyngeal and esophageal swallowing in both conditions with disturbances in timing, clearance, and coordination of swallowing with the respiratory cycle. No participant showed a sensory response such as attempting to clear residue or coughing; thereby supporting the lack of overt symptoms. We conclude that the high death rate from choking and pulmonary infection in children and adults with PWS may be related, in part, to underlying, asymptomatic dysphagia. The combination of rapid eating and dysphagia would increase the risk of aspiration-related morbidity and mortality. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Cognitive and behavioural aspects of Prader-Willi syndrome.

    Science.gov (United States)

    Rice, Lauren J; Einfeld, Stewart L

    2015-03-01

    To provide a review of the recent advances in the diagnosis and treatment of psychiatric disorders in Prader-Willi syndrome (PWS). Research in the last 12 months has provided a descriptive prognosis of psychosis in PWS and highlighted the possible genes associated with the increased risk of psychosis for those with maternal uniparental disomy (mUPD). Several studies investigating social and communication skills have shown people with PWS to have difficulty with core, receptive and expressive language skills, interpreting emotional valence in faces, playing with children of their own age, understanding personal space and a developmental delay in the theory of mind. These social and communication deficits are often more pronounced in those with mUPD. Two recent clinical trials of oxytocin provide mixed results and highlight the need for an improved understanding of the neurobiological characteristics of the PWS brain. A recent pilot study suggests N-acetylcysteine may be a viable treatment for skin picking. Recent advances have contributed to our understanding of the emotional and behavioural problems associated with PWS, and provided directions for further research.

  18. The High Direct Medical Costs of Prader-Willi Syndrome.

    Science.gov (United States)

    Shoffstall, Andrew J; Gaebler, Julia A; Kreher, Nerissa C; Niecko, Timothy; Douglas, Diah; Strong, Theresa V; Miller, Jennifer L; Stafford, Diane E; Butler, Merlin G

    2016-08-01

    To assess medical resource utilization associated with Prader-Willi syndrome (PWS) in the US, hypothesized to be greater relative to a matched control group without PWS. We used a retrospective case-matched control design and longitudinal US administrative claims data (MarketScan) during a 5-year enrollment period (2009-2014). Patients with PWS were identified by Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 759.81. Controls were matched on age, sex, and payer type. Outcomes included total, outpatient, inpatient and prescription costs. After matching and application of inclusion/exclusion criteria, we identified 2030 patients with PWS (1161 commercial, 38 Medicare supplemental, and 831 Medicaid). Commercially insured patients with PWS (median age 10 years) had 8.8-times greater total annual direct medical costs than their counterparts without PWS (median age 10 years: median costs $14 907 vs $819; P < .0001; mean costs: $28 712 vs $3246). Outpatient care comprised the largest portion of medical resource utilization for enrollees with and without PWS (median $5605 vs $675; P < .0001; mean $11 032 vs $1804), followed by mean annual inpatient and medication costs, which were $10 879 vs $1015 (P < .001) and $6801 vs $428 (P < .001), respectively. Total annual direct medical costs were ∼42% greater for Medicaid-insured patients with PWS than their commercially insured counterparts, an increase partly explained by claims for Medicaid Waiver day and residential habilitation. Direct medical resource utilization was considerably greater among patients with PWS than members without the condition. This study provides a first step toward quantifying the financial burden of PWS posed to individuals, families, and society. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Prader-willi syndrome: A case report and a Chinese literature review.

    Science.gov (United States)

    Zhu, Junzhen; Cao, Qinying; Zhang, Ning; Zhao, Lijuan

    2013-11-01

    Prader-Willi syndrome (PWS) is a genetic disorder, resulting from lack of gene expression on the paternally inherited chromosome 15. It is important to determine diagnostic methods for PWS for early treatment. In this study, we report a newborn with Prader-willi syndrome. We further summarized the genetic testing results in the Chinese literature and the relevance of high resolution chromosome and genome-wide copy number variation analysis. There is a heterozygosis deletion of a 5 Mb region in the paternal chromosome 15q11.3-q13.3 by genome-wide copy number variation analysis. However, there is no abnormality in high resolution chromosome karyotype analysis. In conclusion, genome-wide copy number variation analysis is an effective and specific diagnosis method, which will provide scientific evidence for the clinical diagnosis and early treatment of PWS.

  20. Gait patterns in Prader-Willi and Down syndrome patients

    Directory of Open Access Journals (Sweden)

    Albertini Giorgio

    2010-06-01

    Full Text Available Abstract Background Prader-Willi (PWS and Down Syndrome (DS are two genetic disorders characterised by some common clinical and functional features. A quantitative description and comparison of their patterns would contribute to a deeper understanding of the determinants of motor disability in these two syndromes. The aim of this study was to measure gait pattern in PWS and DS in order to provide data for developing evidence-based deficit-specific or common rehabilitation strategies. Methods 19 PWS patients (17.7-40 yr and 21 DS patients (18-39 yr were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of normal-weight controls (Control Group: CG; 33.4 + 9.6 yr. Results and Discussion The results show that PWS and DS are characterised by different gait strategies. Spatio-temporal parameters indicated a cautious, abnormal gait in both groups, but DS walked with a less stable strategy than PWS. As for kinematics, DS showed a significantly reduced hip and knee flexion, especially at initial contact and ankle range of motion than PWS. DS were characterised by lower ranges of motion (p Conclusions Our data show that DS walk with a less physiological gait pattern than PWS. Based on our results, PWS and DS patients need targeted rehabilitation and exercise prescription. Common to both groups is the aim to improve hypotonia, muscle strength and motor control during gait. In DS, improving pelvis and hip range of motion should represent a major specific goal to optimize gait pattern.

  1. Severe tooth wear in Prader-Willi syndrome. A case-control study.

    Science.gov (United States)

    Saeves, Ronnaug; Espelid, Ivar; Storhaug, Kari; Sandvik, Leiv; Nordgarden, Hilde

    2012-05-28

    Prader-Willi syndrome (PWS) is a rare complex multsystemic genetic disorder characterized by severe neonatal hypotonia, endocrine disturbances, hyperphagia and obesity, mild mental retardation, learning disabilities, facial dysmorphology and oral abnormalities. The purpose of the present study was to explore the prevalence of tooth wear and possible risk factors in individuals with Prader-Willi syndrome. Forty-nine individuals (6-40 years) with PWS and an age- and sex-matched control group were included. Tooth wear was evaluated from dental casts and intraoral photographs and rated by four examiners using the Visual Erosion Dental Examination (VEDE) scoring system and the individual tooth wear index IA. In accordance with the VEDE scoring system, tooth wear was also evaluated clinically. Whole saliva was collected. Mean VEDE score was 1.70 ± 1.44 in the PWS group and 0.46 ± 0.36 in the control group (p Prader-Willi syndrome. There is therefore considerable need for prosthodontic rehabilitation in young adults with PWS.

  2. Premature Birth with Complicated Perinatal Course Delaying Diagnosis of Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    G. Ciana

    2011-01-01

    Full Text Available Prader-Willi syndrome in the newborn is essentially characterized by marked hypotonia, feeding difficulties, hypogonadism, and possible characteristic facial features. However, diagnosis at this age may be particularly difficult, and dysmorphic features may be subtle or absent. Prematurity can furthermore delay clinical features recognition and typical complications due to preterm birth may contribute to divert the diagnosis. We describe a preterm baby with a complicated perinatal course later diagnosed as PWS.

  3. Clinical Management of a Child with Prader-Willi Syndrome from Maternal Uniparental Disomy (UPD) Genetic Inheritance

    Science.gov (United States)

    Bellon-Harn, Monica L.

    2005-01-01

    Prader-Willi Syndrome (PWS) is reported in 1 in 10,000-15,000 individuals. Unfortunately, many cases are missed due to clinicians' lack of familiarity with the syndrome as well as clinical and laboratory diagnostic criteria. Although common clinical characteristics are reported, variety exists in the nature and severity of dysfunction associated…

  4. Adult Prader-Willi Syndrome: An Update on Management

    Directory of Open Access Journals (Sweden)

    Luk Ho-Ming

    2016-01-01

    Full Text Available With the advancement of medical care, the survival of most patients with syndromal genetic disease is greatly improved. In this case report, we have reported an adult Prader-Willi syndrome patient who is being diagnosed at the age of 33. The clinical features and their associated complications during adulthood have been reviewed.

  5. Adult Prader-Willi Syndrome: An Update on Management

    OpenAIRE

    Ho-Ming, Luk

    2016-01-01

    With the advancement of medical care, the survival of most patients with syndromal genetic disease is greatly improved. In this case report, we have reported an adult Prader-Willi syndrome patient who is being diagnosed at the age of 33. The clinical features and their associated complications during adulthood have been reviewed.

  6. Sedation in a Patient with Prader-Willi Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Hayrettin Daşkaya

    2014-12-01

    Full Text Available Prader-Willi syndrome (PWS is a rare disorder characterized by hypotonia, growth retardation, characteristic face shape, hypogonadism, hyperphagia and related morbid obesity. Anesthesia application in these patients has increased risk of peroperative complication due the central hypotonia, abnormal teeth structure, and limited neck mobility. Therefore, clinicians should be prepared for the worst scenario before anesthesia application in patients with PWS during general or out-patient surgery. Here, in this case report, outpatient anesthesia performed in a patient with PWS for diagnostic electromyography is presented with the literature review.

  7. Prader-Willi syndrome: a case report with atypical developmental features.

    Science.gov (United States)

    Sewaybricker, Letícia E; Guaragna-Filho, Guilherme; Paula, Georgette B; Andrade, Juliana G R; Tincani, Bruna J; D'Souza-Li, Lília; Lemos-Marini, Sofia H V; Maciel-Guerra, Andréa T; Guerra-Júnior, Gil

    2014-09-01

    To describe the case of a male Prader-Willi syndrome (PWS) patient with atypical development features. We report the case of a male adolescent with confirmed diagnosis of PWS which presents atypical phenotype. The patient progressed with spontaneous and complete pubertal development, stature in the normal range, and weight control without any pharmacological treatment, except metformin. PWS is an imprinting paternally inherited disorder of 15q11-13 characterized by hypotonia in infant age, hyperphagia, varied degrees of mental retardation, behavior problems, hypogonadism, short stature, and other less common findings.

  8. Cognitive, Emotional, Physical and Social Effects of Growth Hormone Treatment in Adults with Prader-Willi Syndrome

    Science.gov (United States)

    Hoybye, C; Thoren, M.; Bohm, B.

    2005-01-01

    Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by short stature, muscular hypotonia, hyperphagia, obesity, maladaptive behaviour, hypogonadism and partial growth hormone (GH) deficiency (GHD). Severe GHD of other aetiologies has been shown to affect mood and quality of life negatively, and there are reports of…

  9. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P

    1997-01-01

    Prader-Willi syndrome (PWS) is a neuroendocrine disorder caused by a non-functioning paternally derived gene(s) within the chromosome region 15q11-q13. Most cases result from microscopically visible deletions of paternal origin, or maternal uniparental disomy of chromosome 15. In both instances n...

  10. IGF-1 levels, complex formation, and IGF bioactivity in growth hormone-treated children with Prader-Willi syndrome

    NARCIS (Netherlands)

    Bakker, N. E.; Van Doorn, J.; Renes, J. S.; Donker, G. H.; Hokken-Koelega, A. C S

    2015-01-01

    Context: Children with Prader-Willi syndrome (PWS) attain high-serum immunoreactive IGF-1 levels during a standard-dose GH treatment, which leads to concern, but lowering the dose deteriorates their body composition. Objective: The objective of the study was to evaluate serum IGF-1, IGF binding

  11. Parental Ratings of Children and Adolescents with Prader-Willi Syndrome on the Behavior Rating Inventory of Executive Function (BRIEF)

    Science.gov (United States)

    Hutchison, Marnie; Pei, Jacqueline; Leung, Wing Sze Wence; Mackenzie, Michelle; Hicks, Melanie D.; Thurm, Audrey E.; Han, Joan C.; Haqq, Andrea M.

    2015-01-01

    We investigated executive functioning in 25 children and adolescents with Prader-Willi syndrome (PWS) on the Behavior Rating Inventory of Executive Function (BRIEF). Significant deficits emerged, with mean scores on all but two scales reaching levels of clinical significance (T score = 65). Older children tended to have higher scores than younger…

  12. Birth prevalence of Prader-Willi syndrome in Australia.

    Science.gov (United States)

    Smith, A; Egan, J; Ridley, G; Haan, E; Montgomery, P; Williams, K; Elliott, E

    2003-03-01

    This is the first population based study to estimate the birth prevalence of DNA proven Prader-Willi syndrome. Thirty infants were reported to the Australian Paediatric Surveillance Unit between 1998 and 2000, a prevalence of 4 per 100,000 live births or approximately 1/25,000 live births per annum.

  13. Prader-Willi syndrome in South African patients clinical and ...

    African Journals Online (AJOL)

    Prader-Willi syndrome in. South African patients clinical and molecular diagnosis. A L Christianson, 0 L Viljoen, W S Winship,. M de la Rey, E J van Rensburg. Study objective. ... This probe detects a parent-of-origin-specific methylation imprint at locus ... These studies were undertaken in the Molecular Genetic. Laboratory of ...

  14. Prader-Willi Syndrome in Two Institutionalized Older Adults.

    Science.gov (United States)

    Goldman, Jeri J.

    1988-01-01

    Two case reports are presented of institutionalized women who were diagnosed as having Prader-Willi syndrome at the ages of 54 and 69. Implications are discussed for management of such persons and for program planning/funding for a much longer life expectancy than earlier realized. (Author/JDD)

  15. Bone mineral density and effects of growth hormone treatment in prepubertal children with Prader-Willi syndrome: a randomized controlled trial.

    NARCIS (Netherlands)

    Lind van Wijngaarden, R.F. de; Festen, D.A.M.; Otten, B.J.; Mil, E.G. van; Rotteveel, J.J.; Odink, R.J.; Leeuwen, M. van; Haring, D.A.; Bocca, G.; Mieke Houdijk, E.C.; Hokken-Koelega, A.C.S.

    2009-01-01

    BACKGROUND: Bone mineral density (BMD) is unknown in children with Prader-Willi syndrome (PWS), but is decreased in adults with PWS. In patients with GH deficiency, BMD increases during GH treatment. OBJECTIVES: The aim of the study was to evaluate BMD in children with PWS and to study the effects

  16. Bone Mineral Density and Effects of Growth Hormone Treatment in Prepubertal Children with Prader-Willi Syndrome : A Randomized Controlled Trial

    NARCIS (Netherlands)

    van Wijngaarden, Roderick F. A. de Lind; Festen, Dederieke A. M.; Otten, Barto J.; van Mil, Edgar G. A. H.; Rotteveel, Joost; Odink, Roelof J.; van Leeuwen, Mariette; Haring, Danny A. J. P.; Bocca, Gianni; Houdijk, E. C. A. Mieke; Hokken-Koelega, Anita C. S.

    2009-01-01

    Background: Bone mineral density (BMD) is unknown in children with Prader-Willi syndrome (PWS), but is decreased in adults with PWS. In patients with GH deficiency, BMD increases during GH treatment. Objectives: The aim of the study was to evaluate BMD in children with PWS and to study the effects

  17. Diagnosis and treatments of Prader-Willi syndrome: a review of current consensuses

    Directory of Open Access Journals (Sweden)

    2014-05-01

    Full Text Available We analyzed international consensuses of experts and clinical recommendations on diagnosis and treatment of Prader-Willi syndrome (PWS: PWS consensus diagnostic criteria (1993; US PWS Association (PWSA-USA consensus statements on evaluating of breathing abnormalities (2007, osteoporosis (2008, growth hormone treatment in PWS (2000 and 2009; Endocrine society clinical practice guideline on Prevention and treatment of pediatric obesity (2008; the Second Expert Meeting of the Comprehensive Care of Patients with PWS Consensus published as Recommendations for the diagnosis and management of PWS (2008. Historical analysis and comparison of recommendations are presented in this review article. Absence of Russian clinical practice guidelines on PWS patients management makes necessary the detailed study of listed documents.

  18. Assessment of Sleep and Breathing in Adults with Prader-Willi Syndrome: A Case Control Series

    Science.gov (United States)

    Yee, Brendon J.; Buchanan, Peter R.; Mahadev, Sri; Banerjee, Dev; Liu, Peter Y.; Phillips, Craig; Loughnan, Georgina; Steinbeck, Kate; Grunstein, Ronald R.

    2007-01-01

    Objectives: Prader-Willi syndrome (PWS) is a genetic disorder (linked to chromosome 15q11-13) characterized by hypotonia and developmental delay, hyperphagia and obesity, hypersomnia and abnormal sleep, and behavioral problems. Such patients may also be at increased risk of obstructive sleep apnea (OSA), although whether this risk is explained by known risk factors has not previously been directly tested. Our aim was to compare sleep and breathing in an older group of patients with Prader-Willi syndrome with a control group—matched on the basis of age, sex, and body mass index (BMI)—in order to determine which specific features are not explained by these known confounders. Methods: Consecutive patients with PWS attending the PWS clinic at Royal Prince Alfred Hospital Sydney, Australia, were recruited. Age-, sex-, and BMI-matched controls were selected from the Sleep Investigation Unit at Royal Prince Alfred Hospital, and polysomnography-derived sleep and other parameters were compared across the groups. Results: Nineteen subjects with PWS (14 males) were included in the study. Eighteen (95 %) had a total respiratory disturbance index (TRDI) of greater than 5 events per hour, with 4 (21%) having severe obstructive sleep apnea (TRDI ≥ 30 events/hour) and 9 (47%) having evidence of obesity hypoventilation syndrome. Patients with PWS, as compared with the control group, had evidence of more nocturnal hypoxemia, with lower oxyhemoglobin saturations and percentages of sleep time at less than 80% oxyhemoglobin saturation (all p values Prader-Willi syndrome: a case control series. J Clin Sleep Med 2007;3(7):713–718. PMID:18198805

  19. The Effects of Muscle Hypotonia and Weakness on Balance: A Study on Prader-Willi and Ehlers-Danlos Syndrome Patients

    Science.gov (United States)

    Galli, Manuela; Cimolin, Veronica; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

    2011-01-01

    Prader-Willi syndrome (PWS) and Ehlers-Danlos syndrome (EDS) are two different genetical disorders both characterized, among other features, by muscular hypotonia. Postural control seems to be impaired in both conditions. The aim of the present study was to quantitatively compare postural control in adult PWS and EDS using stabilometric platform…

  20. Salivary flow rate and oral findings in Prader-Willi syndrome: a case-control study.

    Science.gov (United States)

    Saeves, Ronnaug; Nordgarden, Hilde; Storhaug, Kari; Sandvik, Leiv; Espelid, Ivar

    2012-01-01

    BACKGROUND. Prader-Willi syndrome (PWS) is a rare complex multisystemic genetic disorder. AIM. The objective of this study was to provide a systematic assessment of whole saliva secretion and oral manifestations associated with PWS. DESIGN. Fifty individuals (5-40 years) with PWS and an age- and sex-matched control group were included. Whole saliva was collected. All participants underwent an anamnestic interview. Radiological and dental clinical examinations were carried out to identify hypodontia, dental caries, enamel defects and gingival inflammation. RESULTS. Mean whole salivary flow rate was 0.12 ± 0.11 mL/min in the study group compared with 0.32 ± 0.20 mL/min in the control group (P 19 years was significantly lower in PWS (P = 0.04) compared with the controls. There was no significant difference in the prevalence of dental caries in the primary dentition or in the frequency of enamel defects in the permanent dentition between the two groups. Median Gingival Index was significantly higher in the Prader-Willi group compared with the controls (P = 0.02). CONCLUSIONS. Low salivary flow is a consistent finding in PWS. Nevertheless, despite dry mouth and dietary challenges, dental caries is not increased in Norwegian individuals with PWS. © 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

  1. Motor performance in Prader-Willi syndrome patients and its potential influence on caregiver’s quality of life

    OpenAIRE

    Valeria Jia-Yi Chiu; Li-Ping Tsai; Jang-Ting Wei; I-Shiang Tzeng; Hsin-Chi Wu

    2017-01-01

    Background Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by a variety of physical, cognitive, and behavioral impairments. PWS is a unique sarcopenia model characterized by an abnormal increase in body fat mass and a decrease in muscle mass that predisposes patients to reduced physical activity, functional limitations, and disability. These manifestations may require both symptomatic and supportive management, thus negatively influencing their lifelong fa...

  2. Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: Results of a 2-year crossover GH trial

    NARCIS (Netherlands)

    R.J. Kuppens (Renske); Mahabier, E.F.; N.E. Bakker (Nienke); E.P.C. Siemensma (Elbrich); S.H. Donze (Stephanie); A.C.S. Hokken-Koelega (Anita)

    2016-01-01

    textabstractBackground: Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH)

  3. Scatter Plot Analysis of Excessive Daytime Sleepiness and Severe Disruptive Behavior in Adults with Prader-Willi Syndrome: A Pilot Study

    Science.gov (United States)

    Maas, Anneke P. H. M.; Didden, Robert; Bouts, Lex; Smits, Marcel G.; Curfs, Leopold M. G.

    2009-01-01

    Individuals with Prader-Willi syndrome (PWS) are at risk for excessive daytime sleepiness (EDS) and disruptive behavior. This pilot study explores temporal characteristics of EDS and severe disruptive behavior across time of day and day of week in seven individuals with PWS (aged between 33 and 49 years) of whom five were matched to controls.…

  4. A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Elena G. Bochukova

    2018-03-01

    Full Text Available Summary: Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight disease mechanisms and therapeutic targets. We performed RNA sequencing of hypothalamus from individuals with Prader-Willi syndrome (PWS, a genetic obesity syndrome characterized by severe hyperphagia. We found that upregulated genes overlap with the transcriptome of mouse Agrp neurons that signal hunger, while downregulated genes overlap with the expression profile of Pomc neurons activated by feeding. Downregulated genes are expressed mainly in neuronal cells and contribute to neurogenesis, neurotransmitter release, and synaptic plasticity, while upregulated, predominantly microglial genes are involved in inflammatory responses. This transcriptional signature may be mediated by reduced brain-derived neurotrophic factor expression. Additionally, we implicate disruption of alternative splicing as a potential molecular mechanism underlying neuronal dysfunction in PWS. Transcriptomic analysis of the human hypothalamus may identify neural mechanisms involved in energy homeostasis and potential therapeutic targets for weight loss. : Prader-Willi syndrome (PWS is a genetic obesity syndrome. Bochukova et al. report gene expression changes in the hypothalamus of people with PWS that support neurodegeneration and neuroinflammation as key processes involved in this condition. Keywords: hypothalamus, Prader-Willi syndrome, BDNF, Agrp, obesity, SNORD116

  5. A variety of genetic mechanisms are associated with the Prader-Willi syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Woodage, T.; Deng, Z.M.; Prasad, M. [Royal Prince Alfred Hospital, Camperdown (Australia)] [and others

    1994-09-15

    An extensive set of chromosome 15 DNA polymorphisms and densitometric analysis with four markers mapping to the Prader-Willi chromosome region (PWCR) of chromosome 15 have been used to characterize a cohort of 30 subjects with classical Prader-Willi syndrome (PWS). Molecular analysis enabled the classification of the PWS subjects into four groups: (A) 18 subjects (60%) had deletions of paternal 15q11-13 involving a common set of DNA markers. Two subjects had differently sized deletions, one larger and one smaller than the other cases. (B) Eight (27%) had maternal uniparental disomy for chromosome 15. (C) One (3%) had a marker chromosome carrying an extra copy of the PWCR. The marker chromosome was demonstrated to be of paternal origin and the two intact chromosomes were maternally derived. This case represents an apparent exception to the generally held view that PWS is associated with an absence of paternally inherited gene(s) located in the PWCR. (D) The remaining three cases (10%) had none of the above abnormalities. This last subgroup of patients has not previously been well characterized but could represent limited deletions not detectable with the markers used or abnormalities in the imprinting process. These cases represent potentially valuable resources to elucidate more precisely the fundamental disorders responsible for PWS. 39 refs., 2 figs., 3 tabs.

  6. Gastric Dilatation and Abdominal Compartment Syndrome in a Child with Prader-Willi Syndrome.

    Science.gov (United States)

    Blat, Clara; Busquets, Elisenda; Gili, Teresa; Caixàs, Assumpta; Gabau, Elisabeth; Corripio, Raquel

    2017-06-07

    BACKGROUND Prader-Willi syndrome (PWS) is a genetic disorder characterized by initial muscular hypotonia and feeding difficulties, and later an insatiable appetite, hyperphagia and obesity along with mild to moderate intellectual impairment. Affected individuals' food-seeking behavior and suspected delayed gastric emptying can lead to gastric dilatation with subsequent necrosis and perforation. CASE REPORT We present the case of a 5-year-old boy diagnosed with Prader-Willi syndrome at neonatal age due to muscular hypotonia, who started growth hormone therapy at 20 months. He presented with two episodes of a rapidly progressing gastric dilatation that led to abdominal hypertension and secondary shock at the age of 2 and 5. No large amount of food was eaten before any of the episodes, and he had abdominal pain and vomiting on both occasions. On arrival at the emergency room, a nasogastric tube was placed and aspiration of food material was performed. Abdominal X-ray and CT scan revealed massive gastric dilatation. He was admitted at the Pediatric Intensive Care Unit and after a variable period of fasting, tolerated oral intake and could be discharged. CONCLUSIONS Gastric dilatation due to gastroparesis in PWS is a rare complication. However, it is a life-threatening situation and physicians should therefore maintain a high level of suspicion for gastric dilatation when patients present with warning symptoms such as abdominal pain or discomfort and vomiting.

  7. Severe Short Stature in an Adolescent Male with Prader-Willi Syndrome and Congenital Adrenal Hyperplasia: A Therapeutic Conundrum

    Directory of Open Access Journals (Sweden)

    Meredith Wasserman

    2017-01-01

    Full Text Available Congenital adrenal hyperplasia (CAH due to 21-hydroxylase deficiency results in excess androgen production which can lead to early epiphyseal fusion and short stature. Prader-Willi syndrome (PWS is a genetic disorder resulting from a defect on chromosome 15 due to paternal deletion, maternal uniparental disomy, or imprinting defect. Ninety percent of patients with PWS have short stature. In this article we report a patient with simple-virilizing CAH and PWS who was overtreated with glucocorticoids for CAH and not supplemented with growth hormone for PWS, resulting in a significantly short adult height.

  8. Severe tooth wear in Prader-Willi syndrome. A case–control study

    Directory of Open Access Journals (Sweden)

    Saeves Ronnaug

    2012-05-01

    Full Text Available Abstract Background Prader-Willi syndrome (PWS is a rare complex multsystemic genetic disorder characterized by severe neonatal hypotonia, endocrine disturbances, hyperphagia and obesity, mild mental retardation, learning disabilities, facial dysmorphology and oral abnormalities. The purpose of the present study was to explore the prevalence of tooth wear and possible risk factors in individuals with Prader-Willi syndrome. Methods Forty-nine individuals (6-40 years with PWS and an age- and sex-matched control group were included. Tooth wear was evaluated from dental casts and intraoral photographs and rated by four examiners using the Visual Erosion Dental Examination (VEDE scoring system and the individual tooth wear index IA. In accordance with the VEDE scoring system, tooth wear was also evaluated clinically. Whole saliva was collected. Results Mean VEDE score was 1.70 ± 1.44 in the PWS group and 0.46 ± 0.36 in the control group (p A was 7.50 (2.60-30.70 in the PWS group and 2.60 (0.90-4.70 among controls (p A; r = 0.82, p A; r = 0.43, p = 0.002. Tooth grinding was also associated with tooth wear in the PWS group, as indicated by the mean VEDE 2.67 ± 1.62 in grinders and 1.14 ± 0.97 in non-grinders (p = 0.001 and median IA values 25.70 (5.48-68.55 in grinders and 5.70 (1.60-9.10 in non-grinders (p = 0.003. Multivariate linear regression analysis was performed with tooth wear as the dependent variable and PWS (yes/no, age, tooth grinding and saliva secretion as independent variables. PWS (yes/no, age and tooth grinding retained a significant association with tooth wear, VEDE (p A (p  Conclusions Our study provides evidence that tooth wear, in terms of both erosion and attrition, is a severe problem in Prader-Willi syndrome. There is therefore considerable need for prosthodontic rehabilitation in young adults with PWS.

  9. Prader-Willi Critical Region, a Non-Translated, Imprinted Central Regulator of Bone Mass: Possible Role in Skeletal Abnormalities in Prader-Willi Syndrome.

    Directory of Open Access Journals (Sweden)

    Ee-Cheng Khor

    Full Text Available Prader-Willi Syndrome (PWS, a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR, including a set of small non-translated nucleolar RNA's (snoRNA. Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health

  10. The European Prader-Willi Syndrome Clinical Research Database: An Aid in the Investigation of a Rare Genetically Determined Neurodevelopmental Disorder

    Science.gov (United States)

    Holland, A.; Whittington, J.; Cohen, O.; Curfs, L.; Delahaye, F.; Dudley, O.; Horsthemke, B.; Lindgren, A. -C.; Nourissier, C.; Sharma, N.; Vogels, A.

    2009-01-01

    Background: Prader-Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub-type, age and gender limits clinical studies of sufficient size in any one country. A clinical research…

  11. Hypothalamic growth hormone-releasing hormone (GHRH) cell number is increased in human illness, but is not reduced in Prader-Willi syndrome or obesity

    NARCIS (Netherlands)

    Goldstone, Anthony P.; Unmehopa, Unga A.; Swaab, Dick F.

    2003-01-01

    Acute illness leads to increased GH, but reduced IGF-I secretion, while both are reduced in chronic illness. Prader-Willi syndrome (PWS) is a genetic obesity syndrome, with GH deficiency a feature independent of obesity. Reduced GH secretion may result from decreased hypothalamic release of

  12. Psychotropic treatments in Prader-Willi syndrome: a critical review of published literature.

    Science.gov (United States)

    Bonnot, O; Cohen, D; Thuilleaux, D; Consoli, A; Cabal, S; Tauber, M

    2016-01-01

    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). 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. 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. Topiramate might be efficient for self-injury and impulsive/aggressive behaviors, N-acetyl cysteine is apromising treatment for

  13. High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome

    DEFF Research Database (Denmark)

    DelParigi, Angelo; Tschöp, Matthias; Heiman, Mark L

    2002-01-01

    Prader-Willi syndrome (PWS) is a genetic disorder occurring in 1 of 10,000-16,000 live births and is characterized by excessive appetite with progressive massive obesity as well as short stature and mental retardation. Most patients have GH deficiency and hypogonadotropic hypogonadism. The causes...... of the hyperphagia and abnormal GH secretion are unknown. To determine whether ghrelin, a novel GH secretagogue with orexigenic properties, is elevated in PWS, we measured fasting plasma ghrelin concentration; body composition (dual-energy x-ray absorptiometry); and subjective ratings of hunger (visual analog scale......) in seven subjects (6 males and 1 female; age, 26 +/- 7 yr; body fat, 39 +/- 11%, mean +/- SD) with PWS (diagnosis confirmed by genetic test) and 30 healthy subjects (reference population, 15 males and 15 females; age, 32 +/- 7 yr; body fat, 36 +/- 11%) fasted overnight. All subjects were weight stable...

  14. Decline of CSF orexin (hypocretin) levels in Prader-Willi syndrome.

    Science.gov (United States)

    Omokawa, Mayu; Ayabe, Tadayuki; Nagai, Toshiro; Imanishi, Aya; Omokawa, Ayumi; Nishino, Seiji; Sagawa, Yohei; Shimizu, Tetsuo; Kanbayashi, Takashi

    2016-05-01

    Prader-Willi syndrome is a congenital neurodevelopmental disorder resulting from deletion of the paternal copies of genes within the chromosome region 15q11-q13. Patients with Prader-Willi syndrome often exhibit excessive daytime sleepiness, excessive appetite, and obesity. As is the case in narcolepsy, orexin (hypocretin) may be responsible for these symptoms. However, reports showing cerebrospinal fluid orexin levels in Prader-Willi syndrome patients have been limited. The aim of this study was to examine the relationship between the characteristic symptoms of Prader-Willi syndrome and cerebrospinal fluid orexin levels. We clinically identified 14 Prader-Willi syndrome patients and examined their cerebrospinal fluid orexin levels. A total of 12 patients with a 15q11-q13 deletion and two patients with maternal uniparental disomy of chromosome 15 were identified. A total of 37 narcoleptic patients and 14 idiopathic hypersomnia patients were recruited for comparison. Cerebrospinal fluid orexin levels (median [25-75 percentiles]) in the 14 Prader-Willi syndrome patients were intermediate (192 [161-234.5] pg/ml), higher than in the narcoleptic patients, but lower than in the idiopathic hypersomnia patients. Body mass index of the Prader-Willi syndrome patients was higher than in the narcoleptic and idiopathic hypersomnia patients. There was also a negative correlation between Epworth sleepiness scale scores and orexin levels in Prader-Willi syndrome patients. Decreased cerebrospinal fluid orexin levels in Prader-Willi syndrome may play an important role in severity of obesity and excessive daytime sleepiness. © 2016 Wiley Periodicals, Inc.

  15. Severe obstructive sleep disorders in Prader-Willi syndrome patients in southern Italy.

    Science.gov (United States)

    Canora, Angelo; Franzese, Adriana; Mozzillo, Enza; Fattorusso, Valentina; Bocchino, Marialuisa; Sanduzzi, Alessandro

    2018-01-09

    Sleep-related disordered breathing (SDB) is very common in paediatric patients affected by Prader-Willi Syndrome (PWS). However, data addressing SBD patterns and their management are lacking. The aim of the present study was to analyse SDB features in 14 PWS patients (age range, 8 months-17 years). Polygraphic registration (PG) during a 12-h nocturnal sleep was performed in all patients. Obstructive and central apnoea indices and oxygen saturation (SpO 2 ) were recorded along with demographic and clinical data. Obstructive sleep apnoea (OSA) was diagnosed in 13/14 patients (92.9%); the mean obstructive apnoea-hypopnea index (OAHI) was 7.6 ± 4.2 events/h with a mean central apnoea index (CAI) of 0.7 ± 1.04 events/h. Time spent with SpO 2 Prader-Willi syndrome. What is New: • Severe obstructive sleep apnoea is the most frequent sleep-related disorder in our case series.

  16. Growth hormone usage in Prader-Willi syndrome

    OpenAIRE

    Damiani, Durval

    2008-01-01

    A síndrome de Prader-Willi (PWS), com prevalência de 60:1.000.000, é o resultado da perda de parte do cromossomo 15 paterno, em razão da deleção em 56% dos casos, dissomia uniparental materna em 24% dos casos, ou por causa da metilação, fenômeno epigenético, em 18% dos casos. O quadro clínico inicia-se com profunda hipotonia que, especialmente no primeiro ano de vida, torna difícil a alimentação da criança. Conforme melhora a hipotonia, nos primeiros dois anos, por volta do quarto ano de vida...

  17. Brief Report: Repetitive Behaviour Profiles in Williams Syndrome: Cross Syndrome Comparisons with Prader-Willi and Down Syndromes

    Science.gov (United States)

    Royston, R.; Oliver, C.; Moss, J.; Adams, D.; Berg, K.; Burbidge, C.; Howlin, P.; Nelson, L.; Stinton, C.; Waite, J.

    2018-01-01

    This study describes the profile of repetitive behaviour in individuals with Williams syndrome, utilising cross-syndrome comparisons with people with Prader-Willi and Down syndromes. The Repetitive Behaviour Questionnaire was administered to caregivers of adults with Williams (n = 96), Prader-Willi (n = 103) and Down (n = 78) syndromes. There were…

  18. Cardiovascular and metabolic risk profile and acylation-stimulating protein levels in children with Prader-Willi syndrome and effects of growth hormone treatment

    NARCIS (Netherlands)

    R.F.A. de Lind van Wijngaarden (Roderick); K. Cianflone (Katherine); Y. Gao; R.W.J. Leunissen (Ralph); A.C.S. Hokken-Koelega (Anita)

    2010-01-01

    textabstractContext: Reports on the cardiovascular and metabolic risk profile in children with Prader-Willi syndrome (PWS) and the effects of GH treatment are scarce. Acylation-stimulating protein (ASP) stimulates glucose uptake and triglyceride storage in adipose tissue. Objectives: The aim was to

  19. Relationship between the IQ of People with Prader-Willi Syndrome and that of Their Siblings: Evidence for Imprinted Gene Effects

    Science.gov (United States)

    Whittington, J.; Holland, A.; Webb, T.

    2009-01-01

    Background: Genetic disorders occasionally provide the means to uncover potential mechanisms linking gene expression and physical or cognitive characteristics or behaviour. Prader-Willi syndrome (PWS) is one such genetic disorder in which differences between the two main genetic subtypes have been documented (e.g. higher verbal IQ in one vs.…

  20. Beneficial Effects of Growth Hormone Treatment on Cognition in Children with Prader-Willi Syndrome : A Randomized Controlled Trial and Longitudinal Study

    NARCIS (Netherlands)

    Siemensma, Elbrich P. C.; van Wijngaarden, Roderick F. A. Tummers-de Lind; Festen, Dederieke A. M.; Troeman, Zyrhea C. E.; van Alfen-van der Velden, A. A. E. M. (Janielle); Otten, Barto J.; Rotteveel, Joost; Odink, Roelof J. H.; Bindels-de Heus, G. C. B. (Karen); van Leeuwen, Mariette; Haring, Danny A. J. P.; Oostdijk, Wilma; Bocca, Gianni; Houdijk, E. C. A. Mieke; van Trotsenburg, A. S. Paul; Hoorweg-Nijman, J. J. Gera; van Wieringen, Hester; Vreuls, Rene C. F. M.; Jira, Petr E.; Schroor, Eelco J.; van Pinxteren-Nagler, Evelyn; Pilon, Jan Willem; Lunshof, L. (Bert); Hokken-Koelega, Anita C. S.

    Background: Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited. Methods: Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study during 4 yr

  1. Beneficial effects of growth hormone treatment on cognition in children with Prader-Willi syndrome: a randomized controlled trial and longitudinal study.

    NARCIS (Netherlands)

    Siemensma, E.P.C.; Tummers-de Lind van Wijngaarden, R.F.; Festen, D.A.M.; Troeman, Z.C.; Alfen-van der Velden, A.A.E.M. van; Otten, B.J.; Rotteveel, J.J.; Odink, R.J.; Bindels-de Heus, G.C.; Leeuwen, M. van; Haring, D.A.; Oostdijk, W.; Bocca, G.; Mieke Houdijk, E.C.; Trotsenburg, A.S. van; Hoorweg-Nijman, J.J.G.; Wieringen, H. van; Vreuls, R.C.; Jira, P.E.; Schroor, E.J.; Pinxteren-Nagler, E. van; Willem Pilon, J.; Lunshof, L.B.; Hokken-Koelega, A.C.S.

    2012-01-01

    BACKGROUND: Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited. METHODS: Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study during 4 yr

  2. Beneficial Effects of Growth Hormone Treatment on Cognition in Children with Prader-Willi Syndrome: A Randomized Controlled Trial and Longitudinal Study

    NARCIS (Netherlands)

    Siemensma, Elbrich P. C.; Tummers-de Lind van Wijngaarden, Roderick F. A.; Festen, Dederieke A. M.; Troeman, Zyrhea C. E.; van Alfen-van der Velden, A. A. E. M. Janielle; Otten, Barto J.; Rotteveel, Joost; Odink, Roelof J. H.; Bindels-de Heus, G. C. B. Karen; van Leeuwen, Mariette; Haring, Danny A. J. P.; Oostdijk, Wilma; Bocca, Gianni; Mieke Houdijk, E. C. A.; van Trotsenburg, A. S. Paul; Hoorweg-Nijman, J. J. Gera; van Wieringen, Hester; Vreuls, René C. F. M.; Jira, Petr E.; Schroor, Eelco J.; van Pinxteren-Nagler, Evelyn; Willem Pilon, Jan; Lunshof, L. Bert; Hokken-Koelega, Anita C. S.

    2012-01-01

    Background: Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited. Methods: Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study during 4 yr

  3. Beneficial effects of growth hormone treatment on cognition in children with prader-willi syndrome: A randomized controlled trial and longitudinal study

    NARCIS (Netherlands)

    E.P.C. Siemensma (Elbrich); R.F.A. Tummers-de Lind Van Wijngaarden (Roderick F.); D.A.M. Festen (Dederieke); Z.C.E. Troeman (Zyrhea C.); A.A.E.M. van der Alfen-van Der Velden; B.J. Otten (Barto); J. Rotteveel (Joost); R.J.H. Odink (Roelof); G.C.B. Bindels-de Heus (Karen); M. van Leeuwen (Mariëtte); D.A.J.P. Haring (Danny); W. Oostdijk (Wilma); G. Bocca (Gianni); E.C.A.M. Houdijk (Mieke); A.S.P. van Trotsenburg (Paul); J.J.G. Hoorweg-Nijman (Gera); H. van Wieringen (Hester); R.C.F.M. Vreuls (René); P.E. Jira (Petr); E.J. Schroor (Eelco); E. van Pinxteren-Nagler (Evelyn); J.W. Pilon; S. Lunshof (Simone); A.C.S. Hokken-Koelega (Anita)

    2012-01-01

    textabstractBackground: Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited. Methods: Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study

  4. An 18-year-old patient with Prader-Willi syndrome: a case report on dental management under sedation and general anesthesia

    OpenAIRE

    Song, Ki Un; Nam, Ok Hyung; Kim, Mi Sun; Choi, Sung Chul; Lee, Hyo-Seol

    2015-01-01

    Prader-Willi syndrome (PWS) is a rare genetic disorder reported rarely in dentistry. Dental practitioners should know the features of PWS because affected patients have a variety of dental symptoms. The current report describes a case of PWS. An 18-year-old male patient presented with traumatic injuries. Initial emergency treatments were performed under sedation, and further treatments were conducted under general anesthesia. After adequate healing, periodic follow-up and dietary management a...

  5. Prader-Willi Syndrome: Frequently Asked Questions

    Science.gov (United States)

    ... techniques or tube feeding for several months after birth, until muscle control improves. Sometime in the following years, usually before school age, children with PWS develop an intense interest ...

  6. Congenital hypothyroidism due to ectopic sublingual thyroid gland in Prader-Willi Syndrome: a case report.

    Science.gov (United States)

    Bocchini, Sarah; Fintini, Danilo; Grugni, Graziano; Boiani, Arianna; Convertino, Alessio; Crinò, Antonino

    2017-09-22

    Thyroid gland disorders are variably associated with Prader-Willi syndrome (PWS). Many of the clinical features in newborns with PWS are similar to those found in congenital hypothyroidism (CH). We report a case of a girl with CH and PWS. At the age of 9 months CH caused by an ectopic sublingual thyroid was diagnosed, and hormone replacement therapy was started. In spite of this treatment a decrease in growth velocity, weight excess and delayed development were observed. At the age of 9 years PWS was suspected on the basis of phenotype and genetic tests confirmed a maternal uniparental disomy of chromosome 15. This is the second reported case of hypothyroidism due to an ectopic sublingual thyroid gland in PWS suggesting that, although rare, an association between CH and PWS may exist. In our case diagnosis of PWS was delayed because mental retardation, hypotonia, obesity and short stature were initially attributed to hypothyroidism. In this context PWS should be considered in obese children with CH who do not improve adequately with l-thyroxine therapy. Also, thyroid function in all PWS children should be assessed regularly in order to avoid delayed diagnosis of hypothyroidism.

  7. Near demise of a child with Prader-Willi syndrome during elective orchidopexy.

    Science.gov (United States)

    Mantadakis, Elpis; Spanaki, Anna-Maria; Geromarkaki, Elsa; Vassilaki, Efrosini; Briassoulis, George

    2006-07-01

    The case of a morbidly obese 3.5-year-old boy, with Prader-Willi syndrome (PWS), who experienced a life-threatening episode of pulmonary edema soon after induction of general anesthesia with sevoflurane and intubation for orchidopexy is presented. The patient who had history of sleep apnea and who had an uneventful laparoscopy under general anesthesia 6 months previously was supported with mechanical ventilation with positive end expiratory pressure but developed hyperthermia, pneumonia, sepsis, and Acute Respiratory Distress Syndrome in the intensive care unit. He recovered fully 11 days after surgery. The possible contributing factors for the development of pulmonary edema are discussed. Arrangements for monitoring in an intensive care setting after surgery are highly recommended for patients with PWS.

  8. [Care continuity for patients with Prader-Willi syndrome during transition from childhood to adulthood].

    Science.gov (United States)

    Saitoh, Shinji

    2010-01-01

    Prader-Willi syndrome(PWS) is a complex multisystem genetic disorder, of which characteristic phenotypes include neonatal hypotonia, hyperphagia resulting in obesity, mental retardation, hypogonadism, and behavioral and psychiatric problems. The diagnosis can be obtained as early as during neonatal period thanks to development of genetic testing. Clinical features of PWS will change depending on age, although core phenotypes of hyperphagia, obesity and psychiatric issues stay for lifetime. Therefore, integrated multidisciplinary approach starting from neonatal period is mandatory to ensure optimal management to improve lifelong quality of life. For successful transition from childhood to adulthood, multidisciplinary team need to share clinical information, and should keep the same policy about food, environment and psychiatric issues.

  9. Life Satisfaction Among Mothers of Individuals with Prader-Willi Syndrome.

    Science.gov (United States)

    Shivers, Carolyn M; Leonczyk, Caroline L; Dykens, Elisabeth M

    2016-06-01

    Mothers of individuals with Prader-Willi syndrome (PWS) often experience numerous stressors, even when compared to mothers of children with other intellectual and developmental disabilities. Despite this, these mothers show great variability in self-reported life satisfaction. Using data from a longitudinal study of individuals with PWS and their families, the present study analyzed factors related to maternal life satisfaction, both cross-sectionally and over time. Results show that both child factors (e.g., behavior problems, hyperphagia) and maternal factors (e.g., stress, coping style) were significantly related to maternal life satisfaction. However, none of the tested variables predicted change in life satisfaction over time. Research and practice implications are discussed.

  10. Prader-Willi syndrome: From genetics to behaviour, with special focus on appetite treatments.

    Science.gov (United States)

    Griggs, Joanne L; Sinnayah, Puspha; Mathai, Michael L

    2015-12-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental disorder resulting from a deletion in the expression of the paternally derived alleles in the region of 15q11-q13. PWS has a prevalence rate of 1:10,000-1:30,000 and is characterized by marked endocrine abnormalities including growth hormone deficiency and raised ghrelin levels. The hyperphagic phenotype in PWS is established over a number of phases and is exacerbated by impaired satiety, low energy expenditure and intellectual difficulties including obsessive-compulsive disorder and/or autistic behaviours. Clinical management in PWS typically includes familial/carer restriction and close supervision of food intake. If the supervision of food is left unmanaged, morbid obesity eventuates, central to the risk of cardiorespiratory disorder. None of the current appetite management/intervention strategies for PWS include pharmacological treatment, though recent research shows some promise. We review the established aberrant genetics and the endocrine and neuronal attributes which may determine disturbed regulatory processes in PWS. Focusing on clinical trials for appetite behaviours in PWS, we define the effectiveness of pharmacological treatments with a view to initiating and focusing research towards possible targets for modulating appetite in PWS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Behavioral and emotional manifestations in a child with Prader-Willi syndrome.

    Science.gov (United States)

    Mohapatra, Satyakam; Panda, Udit Kumar

    2016-04-25

    Prader-Willi syndrome is a neurodevelopmental disorder characterized by mental retardation and distinct physical, behavioral, and psychiatric features. Maladaptive behaviours, cognitive impairment, and impediments in speech and language seriously affect the early development and long-term functioning of individuals affected by the illness. We present a case of a 9-year-old child with Prader-Willi syndrome whose behavioural symptoms were treated with low-dose antipsychotic medications.

  12. Phenotype of a child with Angelman syndrome born to a woman with Prader-Willi syndrome.

    Science.gov (United States)

    Ostergaard, John R

    2015-09-01

    This report describes the phenotype, from early childhood to adolescence, of a girl with Angelman syndrome (AS) born following a maternal transmission of a germline paternal 15q11.2-q13 deletion. During early childhood, she showed a typical AS phenotype, such as jerky movements, poor sleep, high voltage electroencephalography pattern, epilepsy, and a severe developmental disability. As she grew older, indications of phenotypical traits similar to Prader-Willi syndrome (PWS) appeared, in particular hyperphagic behavior and a body fat distribution similar to that reported in PWS. She generally showed cheerful AS behavior and had the characteristic outbursts of laughter, but her attitude to other people did not reflect the usual shared enjoyment of interaction seen in children with AS. In unfamiliar surroundings, she withdrew socially, similar to children with PWS, and her insistence on the same, rigid routines was similar to behavior patterns in PWS. The dysmorphic facial features that characterize AS were blurred in adolescence. The specified features that this AS patient had in common with PWS were hardly incidental and, if verified by upcoming case reports of children born to women with a paternal 15q11.2-q13 deletion, they may show new aspects of genetic imprinting. © 2015 Wiley Periodicals, Inc.

  13. [Rapid first-tier genetic diagnosis in patients with Prader-Willi syndrome].

    Science.gov (United States)

    Ács, Orsolya Dóra; Péterfia, Bálint; Hollósi, Péter; Haltrich, Irén; Sallai, Ágnes; Luczay, Andrea; Buiting, Karin; Horsthemke, Bernhard; Török, Dóra; Szabó, András; Fekete, György

    2018-01-01

    According to the international literature, DNA methylation analysis of the promoter region of SNRPN locus is the most efficient way to start genetic investigation in patients with suspected Prader-Willi syndrome. Our aim was to develop a simple, reliable first-tier diagnosis to confirm Prader-Willi syndrome, therefore to compare our self-designed simple, cost-efficient high-resolution melting analysis and the most commonly used methylation-specific multiplex ligation-dependent probe amplification to confirm Prader-Willi syndrome. We studied 17 clinically suspected Prader-Willi syndrome children and their DNA samples. With self-designed primers, bisulfite-sensitive polymerase chain reaction, high-resolution melting analysis and, as a control, methylation-specific multiplex ligation-dependent probe amplification were performed. Prader-Willi syndrome was genetically confirmed in 6 out of 17 clinically suspected Prader-Willi syndrome patients. The results of high-resolution melting analysis and methylation-specific multiplex ligation-dependent probe amplification were equivalent in each case. Using our self-designed primers and altered bisulfite-specific PCR conditions, high-resolution melting analysis appears to be a simple, fast, reliable and effective method for primarily proving or excluding clinically suspected Prade-Willi syndrome cases. Orv Hetil. 2018; 159(2): 64-69.

  14. Prader-Willi Syndrome (PWS): Condition Information

    Science.gov (United States)

    ... Schweizerische Medizinische Wochenschrift, 86, 1260. What are common symptoms? » Related A-Z Topics Intellectual and Developmental Disabilities (IDDs) Obesity and Overweight Autism Spectrum Disorder (ASD) NICHD News Spotlights Experimental therapy for Prader- ...

  15. Prader-Willi Syndrome (PWS): Other FAQs

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    ... OGH) Office of Health Equity (OHE) Office of Legislation and Public Policy (OLPP) Office of Science Policy, ... K., Adam, M. P. (Eds.). Gene reviews . Seattle, WA: University of Washington. Available from http://www.ncbi. ...

  16. New onset epilepsy in Prader-Willi syndrome: semiology and literature review.

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    Benson, Leslie A; Maski, Kiran P; Kothare, Sanjeev V; Bourgeois, Blaise F

    2010-10-01

    Prader-Willi syndrome is a chromosomal disorder caused by absence of expression of the paternal active genes in the 15q11∼q13 chromosome region; it is associated with an increased incidence of epilepsy and narcolepsy. Presented here is the case of a 2.5-year-old boy with Prader-Willi syndrome and a history of neonatal superior sagittal sinus thrombosis with new onset of atonic seizures with electrographic onset from the parasagittal region. It is postulated that microscarring from neonatal venous sinus thrombosis, history of febrile seizures, and Prader-Willi syndrome are factors predisposing him to epilepsy. The importance of video electroencephalography with electromyography electrodes is emphasized for Prader-Willi syndrome patients with drop episodes, to differentiate cataplexy from seizures. This being a novel report of a Prader-Willi syndrome patient with atonic seizures, the literature on seizure semiology among patients with Prader-Willi syndrome is reviewed. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Disorders of Sleep and Ventilatory Control in Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Emily S. Gillett

    2016-07-01

    Full Text Available Prader-Willi syndrome (PWS is an imprinted genetic disorder conferred by loss of paternal gene expression from chromosome 15q11.2-q13. Individuals with PWS have impairments in ventilatory control and are predisposed toward sleep disordered breathing due to a combination of characteristic craniofacial features, obesity, hypotonia, and hypothalamic dysfunction. Children with PWS progress from failure to thrive during infancy to hyperphagia and morbid obesity during later childhood and onward. Similarly, the phenotype of sleep disordered breathing in PWS patients also evolves over time from predominantly central sleep apnea in infants to obstructive sleep apnea (OSA in older children. Behavioral difficulties are common and may make establishing effective therapy with continuous positive airway pressure (CPAP more challenging when OSA persists after adenotonsillectomy. Excessive daytime sleepiness (EDS is also common in patients with PWS and may continue after OSA is effectively treated. We describe here the characteristic ventilatory control deficits, sleep disordered breathing, and excessive daytime sleepiness seen in individuals with PWS. We review respiratory issues that may contribute to sudden death events in PWS patients during sleep and wakefulness. We also discuss therapeutic options for treating sleep disordered breathing including adenotonsillectomy, weight loss, and CPAP. Lastly, we discuss the benefits and safety considerations related to growth hormone therapy.

  18. A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy.

    Science.gov (United States)

    Ludwig, Natasha G; Radaeli, Rafael F; Silva, Mariana M X; Romero, Camila M; Carrilho, Alexandre J F; Bessa, Danielle; Macedo, Delanie B; Oliveira, Maria L; Latronico, Ana Claudia; Mazzuco, Tânia L

    2016-01-01

    Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

  19. Salivary abnormalities in Prader-Willi Syndrome

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    Hart, S.; Poshva, C. [Bowman Gray School of Medicine, Winston-Salem, NC (United States)

    1994-09-01

    Although abnormal saliva is a well documented finding in PWS, little is known about the saliva in these individuals. We have recently undertaken a study to characterize the salivary composition from PW patients and to see if there is any correlation with their underlying molecular diagnosis (deletion vs. disomy). We have collected whole saliva on 3 patients; 2 had normal high-resolution karyotype analysis (Cases 1 & 3) and 1 had a deletion of 15q11q13 (Case 3). For all parameters, Case 3`s values were notably different from those of his unaffected sibling. The salivary flow rates and concentrations for all 3 PW patients are similar and are significantly different from normal controls (mean {plus_minus} SE) (p<0.05). Although this data is from only 3 PW patients, it provides valuable information. First, decreased flow appears to be due to an effect of PWS and not medications since Cases 2 & 3 are not on any medications. Second, decreased flow appears to be present in younger as well as older individuals. Third, deviations from normal in the salivary composition are evident. It is possible that these alterations are concentration effects relative to a decrease in flow rate. We are currently obtaining saliva from more PW individuals to see if these alterations are present in all PW patients and whether they can be applied as a screening test.

  20. The developmental trajectory of disruptive behavior in Down syndrome, fragile X syndrome, Prader-Willi syndrome and Williams syndrome.

    Science.gov (United States)

    Rice, Lauren J; Gray, Kylie M; Howlin, Patricia; Taffe, John; Tonge, Bruce J; Einfeld, Stewart L

    2015-06-01

    The aim of this study was to investigate the developmental trajectories of verbal aggression, physical aggression, and temper tantrums in four genetic syndrome groups. Participants were part of the Australian Child to Adult Development Study (ACAD), which collected information from a cohort of individuals with an intellectual disability at five time points over 18 years. Data were examined from a total of 248 people with one of the four following syndromes: Down syndrome, Fragile X syndrome, Prader-Willi syndrome, or Williams syndrome. Changes in behaviors were measured using validated items from the Developmental Behavior Checklist (DBC). The results indicate that, while verbal aggression shows no evidence of diminishing with age, physical aggression, and temper tantrums decline with age before 19 years for people with Down syndrome, Fragile X syndrome, and William syndrome; and after 19 years for people with Prader-Willi syndrome. These findings offer a somewhat more optimistic outlook for people with an intellectual disability than has previously been suggested. Research is needed to investigate the mechanisms predisposing people with PWS to persistence of temper tantrums and physical aggression into adulthood. © 2015 Wiley Periodicals, Inc.

  1. Systematic review of the clinical and genetic aspects of Prader-Willi syndrome

    Directory of Open Access Journals (Sweden)

    Dong Kyu Jin

    2011-02-01

    Full Text Available Prader-Willi syndrome (PWS is a complex multisystem genetic disorder that is caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11&#8211;q13. This syndrome has a characteristic phenotype including severe neonatal hypotonia, early-onset hyperphagia, development of morbid obesity, short stature, hypogonadism, learning disabilities, behavioral problems, and psychiatric problems. PWS is an example of a genetic condition caused by genomic imprinting. It can occur via 3 main mechanisms that lead to the absence of expression of paternally inherited genes in the 15q11.2&#8211;q13 region: paternal microdeletion, maternal uniparental disomy, and an imprinting defect. Over 99% of PWS cases can be diagnosed using DNA methylation analysis. Early diagnosis of PWS is important for effective long-term management. Growth hormone (GH treatment improves the growth, physical phenotype, and body composition of patients with PWS. In recent years, GH treatment in infants has been shown to have beneficial effects on the growth and neurological development of patients diagnosed during infancy. There is a clear need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy in patients with PWS.

  2. Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics

    Directory of Open Access Journals (Sweden)

    Emma D. Spikol

    2016-03-01

    Full Text Available Prader-Willi syndrome (PWS is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed. Zebrafish, Danio rerio, represent a promising way forward for elucidating physiological problems such as obesity and identifying new pharmacotherapeutic options for PWS. Over the last decade, an increased appreciation for the highly conserved biology among vertebrates and the ability to perform high-throughput drug screening has seen an explosion in the use of zebrafish for disease modeling and drug discovery. Here, we review recent advances in developing zebrafish models of human disease. Aspects of zebrafish genetics and physiology that are relevant to PWS will be discussed, and the advantages and disadvantages of zebrafish models will be contrasted with current animal models for this syndrome. Finally, we will present a paradigm for drug screening in zebrafish that is potentially the fastest route for identifying and delivering curative pharmacotherapies to PWS patients.

  3. Prader-Willi Syndrome: A Case Study and Parent Perspective.

    Science.gov (United States)

    Glaspy, Erin; Foge, Julie

    2015-08-01

    Having a newborn diagnosed with a rare disorder is fraught with many challenges and opportunities for families and healthcare providers alike. This article presents one mother's journey through the daily blessings and challenges of having a child with a rare disorder. Storytelling and reflection interwoven with a case presentation. Prader-Willi syndrome can be a diagnosis that is missed in the immediate postpartum period. Careful assessment and evaluation of the infant is needed. Attention to detail will support an accurate and timely diagnosis. Those involved in the care of infants in the neonatal intensive care unit with special needs owing to a rare disorder must guide families through the difficult process of establishing a diagnosis and coping with the short- and long-term implications of that diagnosis. Research about the needs of families with children with rare diseases is sorely needed. Finding strategies to best support these families is an area of great need.

  4. Scoliosis in patients with Prader Willi Syndrome – comparisons of conservative and surgical treatment

    Directory of Open Access Journals (Sweden)

    Goodall Deborah

    2009-05-01

    Full Text Available Abstract In children with Prader Willi syndrome (PWS, besides growth hormone (GH therapy, control of the food environment and regular exercise, surgical treatment of scoliosis deformities seems the treatment of choice, even though the risks of spinal surgery in this specific population is very high. Therefore the question arises as to whether the risks of spinal surgery outweigh the benefits in a condition, which bears significant risks per se. The purpose of this systematic review of the Pub Med literature was to find mid or long-term results of spinal fusion surgery in patients with PWS, and to present the conservative treatment in a case study of nine patients with this condition. Methods Types of studies included; all kinds of studies; retrospective and prospective ones, which reported upon the outcome of scoliosis surgery in patients with PWS. Types of participants included: patients with scoliosis and PWS. Type of intervention: surgery. Search strategy for identification of the studies; Pub Med; limited to English language and bibliographies of all reviewed articles. Nine patients with PWS from our data-base treated conservatively have been found, being 19 years or over at the time this study has been performed. The results of conservative management are described and related to the natural history and treatment results found in the Pub Med review. Results From 2210 titles displayed in the Pub Med database with the key word being "Prader Willi syndrome", 5 different papers were displayed at the date of the search containing some information on the outcome of surgery and none appeared to contain a mid or long-term follow-up. The PWS patients treated conservatively from our series all stayed below 70° and some of which improved. Discussion If the curve of scoliosis patients with PWS can be kept within certain limits (usually below 70 degrees conservatively, this treatment seems to have fewer complications than surgical treatments. The

  5. A further case of a Prader-Willi syndrome phenotype in a patient with Angelman syndrome molecular defect

    Directory of Open Access Journals (Sweden)

    De Molfetta Greice Andreotti

    2002-01-01

    Full Text Available Angelman syndrome (AS and Prader-Willi syndrome (PWS are distinct human neurogenetic disorders; however, a clinical overlap between AS and PWS has been identified. We report on a further case of a patient showing the PWS phenotype with the AS molecular defect. Despite the PWS phenotype, the DNA methylation analysis of SNRPN revealed an AS pattern. Cytogenetic and FISH analysis showed normal chromosomes 15 and microsatellite analysis showed heterozygous loci inside and outside the 15q11-13 region. The presence of these atypical cases could be more frequent than previously expected and we reinforce that the DNA methylation analysis is important for the correct diagnosis of severe mental deficiency, congenital hypotonia and obesity.

  6. Respiratory Failure due to Severe Obesity and Kyphoscoliosis in a 24-Year-Old Male with Molecularly Confirmed Prader-Willi Syndrome in Tertiary Hospital in Northern Tanzania

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    Elichilia R. Shao

    2017-01-01

    Full Text Available Obesity, mild intellectual disability, hypotonia, poor sucking, cryptorchidism in males, hypogonadism, and kyphoscoliosis are common features of Prader-Willi syndrome (PWS. We report a case who had severe respiratory complications due to extreme obesity and kyphoscoliosis, which are important causes of morbidity and mortality, and discuss management. Furthermore, this is the first molecularly confirmed PWS case in Sub-Saharan Africa outside South Africa.

  7. Obesity and Prader-Willi Syndrome Affect Heart Rate Recovery from Dynamic Resistance Exercise in Youth

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    Diobel M. Castner

    2016-01-01

    Full Text Available Following exercise, heart rate decline is initially driven by parasympathetic reactivation and later by sympathetic withdrawal. Obesity delays endurance exercise heart rate recovery (HRR in both children and adults. Young people with Prader-Willi Syndrome (PWS, a congenital cause for obesity, have shown a slower 60-s endurance exercise HRR compared to lean and obese children, suggesting compromised regulation. This study further evaluated effects of obesity and PWS on resistance exercise HRR at 30 and 60 s in children. PWS (8–18 years and lean and obese controls (8–11 years completed a weighted step-up protocol (six sets x 10 reps per leg, separated by one-minute rest, standardized using participant stature and lean body mass. HRR was evaluated by calculated HRR value (HRRV = difference between HR at test termination and 30 (HRRV30 and 60 (HRRV60 s post-exercise. PWS and obese had a smaller HRRV30 than lean (p < 0.01 for both. Additionally, PWS had a smaller HRRV60 than lean and obese (p = 0.01 for both. Obesity appears to delay early parasympathetic reactivation, which occurs within 30 s following resistance exercise. However, the continued HRR delay at 60 s in PWS may be explained by either blunted parasympathetic nervous system reactivation, delayed sympathetic withdrawal and/or poor cardiovascular fitness.

  8. Assessing the Clinical Utility of SNP Microarray for Prader-Willi Syndrome due to Uniparental Disomy.

    Science.gov (United States)

    Santoro, Stephanie L; Hashimoto, Sayaka; McKinney, Aimee; Mihalic Mosher, Theresa; Pyatt, Robert; Reshmi, Shalini C; Astbury, Caroline; Hickey, Scott E

    2017-01-01

    Maternal uniparental disomy (UPD) 15 is one of the molecular causes of Prader-Willi syndrome (PWS), a multisystem disorder which presents with neonatal hypotonia and feeding difficulty. Current diagnostic algorithms differ regarding the use of SNP microarray to detect PWS. We retrospectively examined the frequency with which SNP microarray could identify regions of homozygosity (ROH) in patients with PWS. We determined that 7/12 (58%) patients with previously confirmed PWS by methylation analysis and microsatellite-positive UPD studies had ROH (>10 Mb) by SNP microarray. Additional assessment of 5,000 clinical microarrays, performed from 2013 to present, determined that only a single case of ROH for chromosome 15 was not caused by an imprinting disorder or identity by descent. We observed that ROH for chromosome 15 is rarely incidental and strongly associated with hypotonic infants having features of PWS. Although UPD microsatellite studies remain essential to definitively establish the presence of UPD, SNP microarray has important utility in the timely diagnostic algorithm for PWS. © 2017 S. Karger AG, Basel.

  9. Puzzle Pieces: Neural Structure and Function in Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Katherine E. Manning

    2015-12-01

    Full Text Available Prader-Willi syndrome (PWS is a neurodevelopmental disorder of genomic imprinting, presenting with a behavioural phenotype encompassing hyperphagia, intellectual disability, social and behavioural difficulties, and propensity to psychiatric illness. Research has tended to focus on the cognitive and behavioural investigation of these features, and, with the exception of eating behaviour, the neural physiology is currently less well understood. A systematic review was undertaken to explore findings relating to neural structure and function in PWS, using search terms designed to encompass all published articles concerning both in vivo and post-mortem studies of neural structure and function in PWS. This supported the general paucity of research in this area, with many articles reporting case studies and qualitative descriptions or focusing solely on the overeating behaviour, although a number of systematic investigations were also identified. Research to date implicates a combination of subcortical and higher order structures in PWS, including those involved in processing reward, motivation, affect and higher order cognitive functions, with both anatomical and functional investigations indicating abnormalities. It appears likely that PWS involves aberrant activity across distributed neural networks. The characterisation of neural structure and function warrants both replication and further systematic study.

  10. Puzzle Pieces: Neural Structure and Function in Prader-Willi Syndrome

    Science.gov (United States)

    Manning, Katherine E.; Holland, Anthony J.

    2015-01-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a behavioural phenotype encompassing hyperphagia, intellectual disability, social and behavioural difficulties, and propensity to psychiatric illness. Research has tended to focus on the cognitive and behavioural investigation of these features, and, with the exception of eating behaviour, the neural physiology is currently less well understood. A systematic review was undertaken to explore findings relating to neural structure and function in PWS, using search terms designed to encompass all published articles concerning both in vivo and post-mortem studies of neural structure and function in PWS. This supported the general paucity of research in this area, with many articles reporting case studies and qualitative descriptions or focusing solely on the overeating behaviour, although a number of systematic investigations were also identified. Research to date implicates a combination of subcortical and higher order structures in PWS, including those involved in processing reward, motivation, affect and higher order cognitive functions, with both anatomical and functional investigations indicating abnormalities. It appears likely that PWS involves aberrant activity across distributed neural networks. The characterisation of neural structure and function warrants both replication and further systematic study. PMID:28943631

  11. Highly restricted deletion of the SNORD116 region is implicated in Prader-Willi Syndrome.

    Science.gov (United States)

    Bieth, Eric; Eddiry, Sanaa; Gaston, Véronique; Lorenzini, Françoise; Buffet, Alexandre; Conte Auriol, Françoise; Molinas, Catherine; Cailley, Dorothée; Rooryck, Caroline; Arveiler, Benoit; Cavaillé, Jérome; Salles, Jean Pierre; Tauber, Maïthé

    2015-02-01

    The SNORD116 locus lies in the 15q11-13 region of paternally expressed genes implicated in Prader-Willi Syndrome (PWS), a complex disease accompanied by obesity and severe neurobehavioural disturbances. Cases of PWS patients with a deletion encompassing the SNORD116 gene cluster, but preserving the expression of flanking genes, have been described. We report a 23-year-old woman who presented clinical criteria of PWS, including the behavioural and nutritional features, obesity, developmental delay and endocrine dysfunctions with hyperghrelinemia. We found a paternally transmitted highly restricted deletion of the SNORD116 gene cluster, the shortest described to date (118 kb). This deletion was also present in the father. This finding in a human case strongly supports the current hypothesis that lack of the paternal SNORD116 gene cluster has a determinant role in the pathogenesis of PWS. Moreover, targeted analysis of the SNORD116 gene cluster, complementary to SNRPN methylation analysis, should be carried out in subjects with a phenotype suggestive of PWS.

  12. Elevated plasma oxytocin levels in children with Prader-Willi syndrome compared with healthy unrelated siblings.

    Science.gov (United States)

    Johnson, Lisa; Manzardo, Ann M; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

    2016-03-01

    Prader-Willi syndrome (PWS) is a rare genetic disorder associated with distinct abnormal behaviors including hyperphagia, profound social deficits, and obsessive-compulsive tendencies. PWS males showed reduced oxytocin receptor (OTR) gene expression and density in the hypothalamic paraventricular nucleus that may play a role in PWS psychopathology. Oxytocin is an anorexigenic neuropeptide similar to vasopressin that is associated with social cognition and obsessive-compulsive behavior. To evaluate oxytocin biology in PWS, we examined overnight fasting plasma oxytocin levels in 23 children with PWS (mean ± SD age: 8.2 ± 2.0 year) having genetic confirmation and 18 age matched healthy unrelated siblings without PWS (mean ± SD age: 8.2 ± 2.3 year) and a similar gender ratio under the same clinical assessments, specimen processing and laboratory conditions. Multiplex immune assays were carried out using the Milliplex Human Neuropeptide Magnetic panel and the Luminex system. Natural log-transformed oxytocin levels were analyzed using general linear model adjusting for diagnosis, gender, age and body mass index (BMI). Oxytocin plasma levels were significantly elevated in children with PWS (168 ± 121 pg/ml) compared with unrelated and unaffected siblings without the diagnosis of PWS (64.8 ± 83.8 pg/ml, F = 8.8, P model fit R(2) = 0.33 (P < 0.01). The symptoms of hyperphagia, anxiety and repetitive behaviors classically seen in PWS may be related to the disruption of oxytocin responsivity or feedback in the hypothalamic paraventricular nucleus possibly influencing vasopressin signaling. Further study is needed to characterize oxytocin function in PWS. © 2015 Wiley Periodicals, Inc.

  13. Identification of Prader-Willi Syndrome mosaicism by fluorescent in situ hybridization

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    Mowery-Rushton, P.A.; Surti, U. [Magee Womens Hospital, Pittsburgh, PA (United States); Hanchett, J.M. [Rehabilitation Institute, Pittsburgh, PA (United States)

    1994-09-01

    Prader-Willi Syndrome (PWS) is a microdeletion syndrome involving an interstitial deletion of region q11-q13 on the paternal chromosome 15. We report 2 cases of PWS that were analyzed using FISH and were found to be mosaic for a normal cell line and a deleted cell line. Case 1 was diagnosed as an atypical PWS who was cytogenetically normal. She is a 38 y.o. white female displaying some but not all of the features of PWS. Case 2 is a 23 y.o. white male with a classical deletion of chromosome 15q11-q13. He displays very typical features of PWS. He was also noted to be albino. FISH analysis was performed on PHA stimulated lymphocytes. We examined four loci: D15S11, SNRPN, D15S10, and GABRB3. The number of cells examined for each locus ranged from 46 to 75. Case 1 was deleted at 3 of the 4 loci (D15S11, SNRPN and GABRB3) in 30% of her cells. The D15S10 locus was not deleted. This may account for the atypical features displayed by this patient. It also suggests that this chromosome is rearranged resulting in the retention of the interstitial locus. The exact nature of the rearrangement needs to be determined. Case 2 was deleted at all four loci in 60% of the cells analyzed. This result was unexpected because his deletion was identified cytogenetically, but mosaicism was not detected. These are the first reported cases of mosaic PWS diagnosed using FISH. The use of cytogenetics alone requires high resolution banding to accurately identify the deletion. This makes the detection of small deletions in every cell difficult and the determination of mosaicism almost impossible. Our results suggest that mosaicism may be occurring more frequently than previously thought and may account for some of the atypical cases. Studies are in progress to determine the effect of mosaicism on methylation at genes located within this region which are imprinted and are thought to be involved in the etiology of Prader-Willi Syndroms.

  14. Weight control and behavior rehabilitation in a patient suffering from Prader Willi syndrome.

    Science.gov (United States)

    Di Lorenzo, Rosaria; Sberveglieri, Sara; Marrama, Donatella; Landi, Giulia; Ferri, Paola

    2016-04-01

    This study reports a case of Prader Willi syndrome (PWS), a genomic imprinting disease related to chromosome regions 15q11.2-q13 15, which includes hypothalamic dysfunction leading to hyperphagia, obesity, shortness, sleep abnormalities. Our case is extremely severe, in comparison to other PWS cases described in literature, due to the association with severe emotional and psychiatric symptoms: oppositional behaviour, rigidity of thought, skin picking and pathological hoarding. We described the case of a Caucasian male patient suffering from PWS, treated in outpatient care by local Mental Health Centre and supported by Social Service, who was admitted to a residential rehabilitative facility. After a 2-year follow-up, the patient showed a global improvement in symptoms and functioning, as registered by the rating scales administered. At the end of observation period, we also reported an important improvement in weight control, reducing the risk of obesity and related diseases, therefore improving the prognosis of life. This case highlights the need for long-term, individualized and multi-professional treatment in patients suffering from a complex genetic syndrome with both organic and psychological alterations, for which medical care setting and pharmacological treatments are not sufficient. Clinical observation of this case leads us to compare PWS to drug addiction and indirectly endorse the neurophysiological hypothesis that food and drugs stimulate the same brain circuits in the limbic system.

  15. The use of medical care and the prevalence of serious illness in an adult Prader-Willi syndrome cohort.

    Science.gov (United States)

    Sinnema, Margje; Maaskant, Marian A; van Schrojenstein Lantman-de Valk, Henny M J; Boer, Harm; Curfs, Leopold M G; Schrander-Stumpel, Constance T R M

    2013-08-01

    Adults with Prader-Willi syndrome (PWS) have an increased occurrence of several medical conditions. We report on the consequences of high morbidity rates such as prevalence rate of hospital admissions, medication use and surgery in a Dutch cohort of adults with PWS. Special attention is paid to causes and symptoms of serious illness. Participants were contacted via the Dutch Prader-Willi Parent Association and through physicians specializing in persons with ID. The persons with PWS and their main caregivers were visited at home. Information was collected through semi-structured interviews on 102 adults with PWS. The need for medical care in the neonatal period is associated with hypotonia and feeding problems. Hospital admissions for respiratory tract infections are frequent. During childhood most hospital admissions were due to PWS syndrome specific surgery. During adolescence hospital admissions occurred for scoliosis surgery and endocrine evaluations. At adult age, hospitalization was associated with inguinal hernia surgery, diabetes mellitus, psychosis, erysipelas, water and drug intoxications. In the older group, respiratory infections were again the main reason for hospital admissions. Frequently used medications at adult age included psychotropics, laxatives, anti-diabetics and dermatologic preparations. Abnormal drinking patterns, problems with anesthesia, decreased ability to vomit, abnormal pain awareness and unpredictable fever responses were frequent and often lead to delayed diagnoses of serious conditions. People with PWS are frequent users of medical-care. Reasons for hospitalization and medication use are age specific. Knowledge on the different presentation of symptoms in people with PWS is needed. In case of unexplained illness, disturbances of consciousness and behavioral changes in people with PWS, an infection should be ruled out in the first place. Information from this study may help in preventing conditions and recognizing conditions in an

  16. Prader-Willi Syndrome: The Disease that Opened up Epigenomic-Based Preemptive Medicine

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    Takeo Kubota

    2016-03-01

    Full Text Available Prader-Willi syndrome (PWS is a congenital neurodevelopmental disorder caused by loss of function of paternally expressed genes on chromosome 15 due to paternal deletion of 15q11–q13, maternal uniparental disomy for chromosome 15, or an imprinting mutation. We previously developed a DNA methylation-based PCR assay to identify each of these three genetic causes of PWS. The assay enables straightforward and rapid diagnosis during infancy and therefore allows early intervention such as nutritional management, physical therapy, or growth hormone treatment to prevent PWS patients from complications such as obesity and type 2 diabetes. It is known that various environmental factors induce epigenomic changes during the perinatal period, which increase the risk of adult diseases such as type 2 diabetes and intellectual disabilities. Therefore, a similar preemptive approach as used in PWS would also be applicable to acquired disorders and would make use of environmentally-introduced “epigenomic signatures” to aid development of early intervention strategies that take advantage of “epigenomic reversibility”.

  17. Assessment of pretend play in Prader-Willi syndrome: a direct comparison to autism spectrum disorder.

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    Zyga, Olena; Russ, Sandra; Ievers-Landis, Carolyn E; Dimitropoulos, Anastasia

    2015-04-01

    Children with Prader-Willi syndrome (PWS) are at risk for autism spectrum disorder (ASD), including pervasive social deficits. While play impairments in ASD are well documented, play abilities in PWS have not been evaluated. Fourteen children with PWS and ten children with ASD were administered the Autism Diagnostic Observation Schedule (ADOS) (Lord et al. in Autism Diagnostic Observation Schedule manual. Western Psychological Services, Los Angeles, 2006) as part of a larger project. A modified Affect in Play Scale (APS; Russ in Play in child development and psychotherapy: toward empirically supported practice. Lawrence Erlbaum Associates Publishers, Mahwah, 2004; Pretend play in childhood: foundation of adult creativity. APA Books, Washington, 2014) was used to score ADOS play activities. Results indicate both groups scored below normative data on measures of imagination, organization, and affective expression during individual play. In addition, the inclusion of a play partner in both groups increased all scaled scores on the APS. These findings suggest children with PWS show impaired pretend play abilities similar to ASD. Further research is warranted and should focus on constructing and validating programs aimed at improving symbolic and functional play abilities within these populations.

  18. MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings

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    Miller, L. [Dept. of Radiology, Winthrop University Hospital, Mineola, NY (United States); Angulo, M. [Dept. of Pediatrics, Div. of Endocrinology and Genetics, Winthrop University Hospital, Mineola, NY (United States); Price, D. [Dept. of Radiology, Winthrop University Hospital, Mineola, NY (United States); Taneja, S. [Dept. of Radiology, Winthrop University Hospital, Mineola, NY (United States)

    1996-01-01

    Prader-Willi syndrome (PWS) is an unusual genetic disorder characterized by short stature, obesity, hypogonadism, hypotonia, cognitive impairment, and dysmorphic facies. There is an interstitial deletion of the proximal long arm of chromosome 15 in about 70% of patients. Some of these clinical features suggest a central hypothalamic/pituitary dysfunction, and recent investigations have demonstrated a marked impairment in spontaneous growth hormone (GH) secretion. We studied 15 GH-deficient PWS patients by magnetic resonance imaging (MRI) to determine whether there was a diminution in the gross morphological size of the anterior pituitary gland, the site of GH synthesis. We also set out to catalog the pertinent imaging findings in this patient population. Our results indicate that this is the first report documenting pituitary size by MRI in PWS patients. No statistically significant difference was found in the height of the anterior pituitary gland in PWS patients compared with either normal children or children with isolated GH deficiency. An interesting imaging finding is that three of 15 patients (20%) demonstrated complete absence of the posterior pituitary bright spot (PPBS), and a fourth patient demonstrated a small PPBS. These observations reflect an objective physiologic disturbance in the hypothalamus. The clinical and radiologic implications of these findings are discussed. (orig.)

  19. Good cognitive performances in a child with Prader-Willi syndrome.

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    Nugnes, Rosa; Zito, Eugenio; Mozzillo, Enza; Camarca, Maria Erminia; Riccio, Maria Pia; Terrone, Gaetano; Melis, Daniela; Bravaccio, Carmela; Franzese, Adriana

    2013-11-15

    We report the case of a child affected by Prader-Willi syndrome (PWS) with good cognitive performances and without relevant behavioral abnormalities.The diagnosis of PWS, suspected on the basis of clinical features and past history, was confirmed by DNA methylation analysis. Additional genetic testing revealed a maternal uniparental disomy. Intellectual profile was analyzed by WISC-III and Raven's Progressive Matrices CPM, while the behavior was evaluated by K-SADS-PL and Child Behavior Checklist/4-18 to the parents.WISC-III test showed a Total Intelligence Quotient (T-IQ = 79) at the border level for age. The Verbal Intelligence Quotient (V-IQ) showed a lower score than the Performance Intelligence Quotient (P-IQ) (78 and 85, respectively). Raven's Matrices CPM showed an intelligence level at 75-90° percentile for age. Concerning behavioral evaluation, a difficulty in impulse control was observed, with persistent but controllable search for food, without a clear psychopathological meaning. Also according to K-SADS-PL no areas of psychopathological dimensions were detected. In conclusion, in presence of consisting clinical features of PWS and high diagnostic suspicion, the diagnosis of PWS should be considered even in presence of a borderline IQ and in absence of psychopathological abnormalities.

  20. High unacylated ghrelin levels support the concept of anorexia in infants with prader-willi syndrome.

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    Beauloye, Veronique; Diene, Gwenaelle; Kuppens, Renske; Zech, Francis; Winandy, Coralie; Molinas, Catherine; Faye, Sandy; Kieffer, Isabelle; Beckers, Dominique; Nergårdh, Ricard; Hauffa, Berthold; Derycke, Christine; Delhanty, Patrick; Hokken-Koelega, Anita; Tauber, Maithé

    2016-05-04

    Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with different nutritional phases from suckling deficit with failure to thrive to early onset of obesity. Hyperghrelinemia has been described in PWS long before the development of obesity. Ghrelin is found in both acylated (AG) and unacylated (UAG) forms in the circulation. In contrast to AG, UAG has been shown to inhibit food intake and to be elevated in anorexia nervosa. The present project is aiming to determine the underlying mechanisms driving the different nutritional phases in PWS. Measurement of at least 4 h-fasting plasma acylated and unacylated ghrelin in 37 infants with a genetic diagnosis of PWS aged from 1 month to 4 years and in 100 age-matched controls without endocrine disorder recruited prior to minor surgery. One blood sampling was analysed for each patient/control and clinical data were recorded. Eleven PWS infants underwent repetitive blood samples at 3 or 6-month intervals during routine visits. In infants with PWS, AG is not elevated (p = 0.45), UAG is significantly higher (p = 0.0044; confidence interval 1.06;1.33) resulting in a low AG/UAG ratio (p = 0.0056; confidence interval 0.76;0.95) compared to controls. Unlike children and adults with PWS that have high AG and AG/UAG ratio, infants with PWS have elevated UAG that supports the concept of anorexia in the early phases of the disease. The change in AG/UAG ratio possibly drives the switch from failure to thrive to obesity. NCT02529085 .

  1. Birth seasonality in Korean Prader-Willi syndrome with chromosome 15 microdeletion

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    Aram Yang

    2015-03-01

    Full Text Available PurposePrader-Willi syndrome (PWS is a well-known genetic disorder, and microdeletion on chromosome 15 is the most common causal mechanism. Several previous studies have suggested that various environmental factors might be related to the pathogenesis of microdeletion in PWS. In this study, we investigated birth seasonality in Korean PWS.MethodsA total of 211 PWS patients born from 1980 to 2014 were diagnosed by methylation polymerase chain reaction at Samsung Medical Center. Of the 211 patients, 138 were born from 2000-2013. Among them, the 74 patients of a deletion group and the 22 patients of a maternal uniparental disomy (UPD group were compared with general populations born from 2000 using the Walter and Elwood method and cosinor analysis.ResultsThere was no statistical significance in seasonal variation in births of the total 211 patients with PWS (χ2=7.2522, P=0.2982. However, a significant difference was found in the monthly variation between PWS with the deletion group and the at-risk general population (P<0.05. In the cosinor model, the peak month of birth for PWS patients in the deletion group was January, while the nadir occurred in July, with statistical significance (amplitude=0.23, phase=1.2, low point=7.2. The UPD group showed the peak birth month in spring; however, this result was not statistically significant (χ2=3.39, P=0.1836.ConclusionCorrelation with birth seasonality was identified in a deletion group of Korean PWS patients. Further studies are required to identify the mechanism related to seasonal effects of environmental factors on microdeletion on chromosome 15.

  2. An 18-year-old patient with Prader-Willi syndrome: a case report on dental management under sedation and general anesthesia.

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    Song, Ki Un; Nam, Ok Hyung; Kim, Mi Sun; Choi, Sung Chul; Lee, Hyo-Seol

    2015-12-01

    Prader-Willi syndrome (PWS) is a rare genetic disorder reported rarely in dentistry. Dental practitioners should know the features of PWS because affected patients have a variety of dental symptoms. The current report describes a case of PWS. An 18-year-old male patient presented with traumatic injuries. Initial emergency treatments were performed under sedation, and further treatments were conducted under general anesthesia. After adequate healing, periodic follow-up and dietary management according to the patient's age and nutritional phase were recommended. Dental management of PWS patients consists of active preventive measures in addition to dietary consultation according to age and nutritional phase.

  3. Assessment of fat-free mass from bioelectrical impedance analysis in obese women with Prader-Willi syndrome.

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    Bedogni, Giorgio; Grugni, Graziano; Tringali, Gabriella; Agosti, Fiorenza; Sartorio, Alessandro

    2015-01-01

    Fat-free mass (FFM) is lower in obese subjects with Prader-Willi syndrome (PWS) than in obese subjects without PWS. FFM prediction equations developed in non-PWS subjects may, thus, not work in PWS subjects. To test whether the estimation of FFM from bioelectrical impedance analysis (BIA) in PWS subjects requires population-specific equations. Using dual-energy X-ray absorptiometry, this study measured FFM in 27 PWS and 56 non-PWS obese women and evaluated its association with the impedance index at 50 kHz (ZI50), i.e. the ratio between squared height and whole-body impedance at 50 kHz. At the same level of ZI50, PWS women had a lower FFM than non-PWS women. However, when PWS-specific equations were used, FFM was accurately estimated at the population level. An equation employing a dummy variable coding for PWS status was able to explain 85% of the variance of FFM with a root mean squared error of 3.3 kg in the pooled sample (n = 83). Population-specific equations are needed to estimate FFM from BIA in obese PWS women.

  4. The neurobiological drive for overeating implicated in Prader-Willi syndrome.

    Science.gov (United States)

    Zhang, Yi; Wang, Jing; Zhang, Guansheng; Zhu, Qiang; Cai, Weiwei; Tian, Jie; Zhang, Yi Edi; Miller, Jennifer L; Wen, Xiaotong; Ding, Mingzhou; Gold, Mark S; Liu, Yijun

    2015-09-16

    Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous fMRI studies examined the activation of eating-related neural circuits in PWS patients with or without exposures to food cues and found an excessive eating motivation and a reduced inhibitory control of cognitive processing of food. However, the effective connectivity between various brain areas or neural circuitry critically implicated in both the biological and behavioral control of overeating in PWS is largely unexplored. The current study combined resting-state fMRI and Granger causality analysis (GCA) techniques to investigate interactive causal influences among key neural pathways underlying overeating in PWS. We first defined the regions of interest (ROIs) that demonstrated significant alterations of the baseline brain activity levels in children with PWS (n = 21) as compared to that of their normal siblings controls (n = 18), and then carried out GCA to characterize the region-to-region interactions among these ROIs. Our data revealed significantly enhanced causal influences from the amygdala to the hypothalamus and from both the medial prefrontal cortex and anterior cingulate cortex to the amygdala in patients with PWS (P < 0.001). These alterations offer new explanations for hypothalamic regulation of homeostatic energy intake and impairment in inhibitory control circuit. The deficits in these dual aspects may jointly contribute to the extreme hyperphagia in PWS. This study provides both a new methodological and a neurobiological perspective to aid in a better understanding of neural mechanisms underlying obesity in the general public. This article is part of a Special Issue entitled 1618. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Comparative analysis of autistic traits and behavioral disorders in Prader-Willi syndrome and Asperger disorder.

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    Song, Dae Kwang; Sawada, Masayuki; Yokota, Shingo; Kuroda, Kenji; Uenishi, Hiroyuki; Kanazawa, Tetsufumi; Ogata, Hiroyuki; Ihara, Hiroshi; Nagai, Toshiro; Shimoda, Kazutaka

    2015-01-01

    Prader-Willi syndrome (PWS) is a neuro-genetic disorder caused by the absence/loss of expression of one or more paternally expressed genes on chromosome 15 (q11-13). In this study, a comparative analysis of intelligence level and autistic traits was conducted between children with PWS (n = 30; 18 males, 12 females; age = 10.6 ± 2.8 years) and those with Asperger disorder (AD; n = 31; 24 males, 7 females; age = 10.5 ± 3.1 years). The children were compared by age group: lower elementary school age (6-8 years), upper elementary school age (9-12 years), and middle school age (13-15 years). As results, the intelligence levels of children with PWS were significantly lower than those with AD across all age groups. Autistic traits, assessed using the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS), revealed that among elementary school age children, those with PWS had less prominent autistic traits than those with AD, however, among middle school age children, those with PWS and AD showed similar prominence. An analysis of the PARS subscale scores by age group showed that while the profiles of autistic traits for children with PWS differed from those of children with AD at elementary school age, the profiles showed no significant differences between the groups at middle school age. The findings suggest that autistic traits in PWS become gradually more prominent with increasing of age and that these autistic traits differ in their fundamental nature from those observed in AD. © 2014 Wiley Periodicals, Inc.

  6. Severe neonatal-onset panniculitis in a female infant with Prader-Willi syndrome.

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    Sakthivel, Muthukumar; Hughes, Stephen M; Riley, Phil; Arkwright, Peter D; Mukherjee, Anindya; Ramsden, Simon; Urquhart, Jill; Crow, Yanick J

    2011-12-01

    The panniculitides are a group of heterogeneous inflammatory diseases involving the subcutaneous fat, the pathogenesis of which is poorly understood. Here, we report on a female infant with Prader-Willi syndrome who developed a systemic inflammatory disorder in the neonatal period demonstrating recurrent panniculitis as a prominent feature. This is the second report of an association between Prader-Willi syndrome and panniculitis. Such an association might be explained by the unmasking of a recessive allele as a consequence of hemizygosity, in the case of a 15q11 deletion, or homozygosity, in the case of maternal isodisomy. Copyright © 2011 Wiley Periodicals, Inc.

  7. Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development.

    Science.gov (United States)

    Miller, Nichol L G; Wevrick, Rachel; Mellon, Pamela L

    2009-01-15

    Prader-Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS.

  8. Effects of Adiposity and Prader-Willi Syndrome on Postexercise Heart Rate Recovery

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    Diobel M. Castner

    2013-01-01

    Full Text Available Heart rate recovery (HRR is an indicator of all-cause mortality in children and adults. We aimed to determine the effect of adiposity and Prader-Willi Syndrome (PWS, a congenital form of obesity, on HRR. Sixteen children of normal weight (NW = body fat % ≤85th percentile, 9.4 ± 1.1 y, 18 children with obesity (OB = body fat % >95th percentile, 9.3 ± 1.1 y, and 11 PWS youth (regardless of body fat %; 11.4 ± 2.5 y completed peak and submaximal bike tests on separate visits. HRR was recorded one minute following peak and submaximal exercises. All groups displayed similar HRR from peak exercise, while NW (54 ± 16 beats and OB (50 ± 12 beats exhibited a significantly faster HRR from submaximal exercise than PWS (37 ± 14 beats. These data suggest that excess adiposity does not influence HRR in children, but other factors such as low cardiovascular fitness and/or autonomic dysfunction might be more influential.

  9. First Case Report of Prader-Willi-Like Syndrome in Colombia.

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    Candelo, Estephania; Feinstein, Max M; Ramirez-Montaño, Diana; Gomez, Juan F; Pachajoa, Harry

    2018-01-01

    Background: Prader-Willi-like syndrome (PWLS) is believed to be caused by a variety of disruptions in genetic pathways both inside and outside of the genetic region implicated in PWS. By definition, PWLS does not demonstrate mutations in the 15q11-q13 region itself. It is a rare disorder whose clinical hallmarks include hypotonia, obesity, short extremities, and delayed development. This syndrome has been described in patients with 1p, 2p, 3p, 6q, and 9q chromosome abnormalities and in cases with maternal uniparental disomy of chromosome 14 and fragile X syndrome. Case presentation: In the present report, we describe a 9-year-old Colombian patient who demonstrated features of PWS and was ultimately diagnosed with PWLS after genetic analysis revealed a 14.97 Mb deletion of 6q16.1-q21. Conclusions: This is the first reported case of PWLS in Colombia and represents one of the largest documented 6q21 deletions.

  10. Venovenous Extracorporeal Membrane Oxygenation in an Adult Patient With Prader-Willi Syndrome: A Nutrition Case Report.

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    Pelekhaty, Stacy; Menaker, Jay

    2018-03-12

    Prader-Willi Syndrome (PWS) is a genetic condition that results in a constellation of symptoms and typically results in hyperphagia and obesity in adulthood. Critically ill adults with PWS present a unique challenge to the nutrition professional, particularly when they require support modalities such as extracorporeal membrane oxygenation (ECMO). The purpose of this case study is to review the nutrition care of a critically ill adult patient with PWS who required venovenous ECMO. The patient was successfully managed with a hypocaloric, high-protein approach, which did not result in the diagnosis of malnutrition during his hospitalization. The patient was ultimately transitioned off extracorporeal life support and discharged to a rehabilitation facility. © 2018 American Society for Parenteral and Enteral Nutrition.

  11. Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome.

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    Dykens, Elisabeth M; Miller, Jennifer; Angulo, Moris; Roof, Elizabeth; Reidy, Michael; Hatoum, Hind T; Willey, Richard; Bolton, Guy; Korner, Paul

    2018-06-21

    Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder of life-threatening hyperphagia, obesity, intellectual deficits, compulsivity, and other behavioral problems. The efficacy and safety of i.n. carbetocin, an oxytocin analog, was evaluated in a prospective, randomized, double-blinded trial in adolescents with PWS. Eligible patients aged 10-18 years with genetically confirmed PWS were randomized (1:1) to i.n. carbetocin or placebo 3 times daily for 14 days. The primary efficacy endpoint was change in parent/caregiver-rated Hyperphagia in PWS Questionnaire-Responsiveness (HPWSQ-R) total score. Secondary efficacy endpoints included HPWSQ-R behavior, drive, and severity domains; clinician-rated HPWSQ; Children's Yale-Brown Obsessive-Compulsive Severity Scale; food domain of the Reiss Profile; and Clinical Global Impression-Improvement scale. Endpoints were assessed using analysis of covariance. Relationship between primary and secondary endpoints was assessed using Pearson correlation coefficients. Safety was assessed throughout the study. Demographics and clinical characteristics were similar between treatment groups (carbetocin, n = 17; placebo, n = 20). Patients receiving carbetocin had statistically significant reductions in HPWSQ-R total score at study end (-15.6) versus patients receiving placebo (-8.9; P = 0.029); several secondary efficacy endpoints also demonstrated significant differences (P primary and secondary endpoints were highly correlated (P ≤ 0.0001). Incidence of adverse events (AEs) was similar between treatment groups. I.n. carbetocin was well tolerated and improved hyperphagia and behavioral symptoms of PWS. ClinicalTrials.gov: NCT01968187FUNDING. The study was funded by Ferring Pharmaceuticals. Recruitment was aided by ongoing work in PWS performed through Eunice Kennedy Shriver National Institute of Child Health and Human Development grant U54 HD083211.

  12. Divergent structural brain abnormalities between different genetic subtypes of children with Prader-Willi syndrome.

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    Lukoshe, Akvile; White, Tonya; Schmidt, Marcus N; van der Lugt, Aad; Hokken-Koelega, Anita C

    2013-10-22

    Prader-Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD.

  13. Sex and Genes, Part 1: Sexuality and down, Prader-Willi, and Williams Syndromes

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    Watson, Shelley Lynn; Richards, Deborah A.; Miodrag, Nancy; Fedoroff, J. Paul

    2012-01-01

    Specific genetic syndromes affect individuals' sexual development, experiences, and fertility. Individuals with specific syndromes can also display inappropriate sexual behavior resulting from vulnerabilities presented by their genetic makeup. Using clinical case studies, we discuss the specific impact that Down, Prader-Willi, and Williams…

  14. Mosaicism for maternal uniparental disomy 15 in a boy with some clinical features of Prader-Willi syndrome.

    Science.gov (United States)

    Zilina, Olga; Kahre, Tiina; Talvik, Inga; Oiglane-Shlik, Eve; Tillmann, Vallo; Ounap, Katrin

    2014-01-01

    Prader-Willi syndrome (PWS) is caused by the lack of paternal expression of imprinted genes in the human chromosomal region 15q11.2-q13.2, which can be due to an interstitial deletion at 15q11.2-q13 of paternal origin (65-75%), maternal uniparental disomy (matUPD) of chromosome 15 (20-30%), or an imprinting defect (1-3%). The majority of PWS-associated matUPD15 cases represent a complete heterodisomy of chromosome 15 or a mixture of hetero- and isodisomic regions across the chromosome 15. Pure maternal isodisomy is observed in only a few matUPD15 patients. Here we report a case of an 18-year-old boy with some clinical features of Prader-Willi syndrome, such as overweight, muscular hypotonia, facial dysmorphism and psychiatric problems, but there was no reason to suspect PWS in the patient based solely on the phenotype estimation. However, chromosomal microarray analysis (CMA) revealed mosaic loss of heterozygosity of the entire chromosome 15. Methylation-specific multiplex ligation-dependant probe amplification (MS-MLPA) analysis showed hypermethylation of the SNRPN and NDN genes in the PWS/AS critical region of chromosome 15 in this patient. Taking into consideration the MS-MLPA results and the presence of PWS features in the patient, we concluded that it was matUPD15, although the patient's parents were not enrolled in the study. According to CMA and karyotyping, no trisomic or monosomic cells were present. To the best of our knowledge, only two PWS cases with mosaic maternal isodisomy 15 and without trisomic/monosomic cell lines have been reported so far. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. An unusual case of adolescent type 2 diabetes mellitus: Prader-Willi syndrome

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    Riyas Basheer

    2016-01-01

    Full Text Available Prader-Willi syndrome (PWS is a complex genetic disorder, characterized by neonatal hypotonia, developmental delay, short stature, childhood obesity, hypogonadism, and characteristic facial features. Here we report a 21-year-old male who presented with uncontrolled glycemic status. He was diagnosed to have diabetes mellitus at the age of 15 with osmotic symptoms - polyuria, polydipsia, and polyphagia. In the early period, after diagnosis, his blood sugars were reasonably controlled with oral hypoglycemic agents. However, a year back, he was switched onto insulin therapy due to secondary OHA failure. On examination, his body mass index was 36 kg/m 2 . He had bilateral gynecomastia, decreased biparietal diameter, almond shaped eyes with esotropia. He had hypogonadism and also had mild cognitive impairment. He did not have any proximal myopathy or other focal neurological deficits. Hormonal evaluation showed low testosterone and inappropriately normal fluorescence in situ hybridization suggestive of central hypogonadism. With fetal and neonatal hypotonia, delayed developmental milestones, hypogonadism, and early onset diabetes, he fulfilled the clinical criteria for the diagnosis of PWS. Multidisciplinary approach of clinicians together with family and social support are essential to bring out the optimal outcome for such syndromic cases.

  16. An unusual case of adolescent type 2 diabetes mellitus: Prader-Willi syndrome.

    Science.gov (United States)

    Basheer, Riyas; Jalal, Muhammed Jasim Abdul; Gomez, Ramesh

    2016-01-01

    Prader-Willi syndrome (PWS) is a complex genetic disorder, characterized by neonatal hypotonia, developmental delay, short stature, childhood obesity, hypogonadism, and characteristic facial features. Here we report a 21-year-old male who presented with uncontrolled glycemic status. He was diagnosed to have diabetes mellitus at the age of 15 with osmotic symptoms - polyuria, polydipsia, and polyphagia. In the early period, after diagnosis, his blood sugars were reasonably controlled with oral hypoglycemic agents. However, a year back, he was switched onto insulin therapy due to secondary OHA failure. On examination, his body mass index was 36 kg/m(2). He had bilateral gynecomastia, decreased biparietal diameter, almond shaped eyes with esotropia. He had hypogonadism and also had mild cognitive impairment. He did not have any proximal myopathy or other focal neurological deficits. Hormonal evaluation showed low testosterone and inappropriately normal fluorescence in situ hybridization suggestive of central hypogonadism. With fetal and neonatal hypotonia, delayed developmental milestones, hypogonadism, and early onset diabetes, he fulfilled the clinical criteria for the diagnosis of PWS. Multidisciplinary approach of clinicians together with family and social support are essential to bring out the optimal outcome for such syndromic cases.

  17. Prader-Willie Syndrome in the Practice of Pediatrician. Modern Approaches to the Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    T.M. Khimenko

    2015-05-01

    Full Text Available Objective. To familiarize the doctors with diagnostic criteria and modern comprehensive approach to the treatment of children with Prader-Willie syndrome. The problems of treatment with growth hormone, social integration of patients were stressed, a clinical case from practice is presented. The analysis of the scientific literature of leading foreign and domestic authors has been carried out. The article presents the current approaches to early diagnosis based on large and small diagnostic criteria already at the first months of life, indications for molecular-genetic testing by fish-method to detect microdeletions of chromosome 15. A case of Prader-Willi syndrome demonstrates the typical clinical manifestations, the need for a multidisciplinary approach and continuous monitoring of patients. Conclusions. Prader-Willi syndrome has characteristic features that can be detected in most patients during the first six months of life, which will made it possible to carry out timely correction of metabolic and hormonal disorders and to improve quality of life. To clarify the diagnosis, genetic testing, which today became available in most regions of Ukraine, is successfully performed. The question of supporting hormone therapy that enables to adjust significantly the phenotype of patients with Prader-Willi syndrome, providing adequate physical development, is still open. Long-term use of recombinant growth hormone can prevent a number of complications characteristic of the syndrome, and to improve the quality of life for patients in the future.

  18. Synchrony of oculocutaneous albinism, the Prader-Willi syndrome, and a normal karyotype.

    Science.gov (United States)

    Wallis, C E; Beighton, P H

    1989-01-01

    A Chinese girl with oculocutaneous albinism has the Prader-Willi syndrome and a normal karyotype. This association emphasises the importance of further molecular study of the 15(q12) region of the genome in the search for the locus of an albinism gene. Images PMID:2732995

  19. Treatment of Covert Food Stealing in an Individual with Prader-Willi Syndrome.

    Science.gov (United States)

    Maglieri, Kristen, A.; DeLeon, Iser G.; Rodriguez-Catter, Vanessa; Sevin, Bart M.

    2000-01-01

    A study found verbal reprimands, delivered contingent upon eating prohibited foods, were sufficient to decease the food stealing of a girl (age 14) with Prader-Willi syndrome. Warning stimuli were then successfully used to help her discriminate between permitted/prohibited foods during sessions in which food stealing was not directly observed.…

  20. A Mindfulness-Based Health Wellness Program for an Adolescent with Prader-Willi Syndrome

    Science.gov (United States)

    Singh, Nirbhay N.; Lancioni, Giulio E.; Singh, Ashvind N.; Winton, Alan S. W.; Singh, Judy; McAleavey, Kristen M.; Adkins, Angela D.

    2008-01-01

    Individuals with Prader-Willi syndrome have hyperphagia, a characteristic eating disorder defined by a marked delay in the satiety response when compared to controls. This eating disorder has been particularly difficult to control. The authors taught and evaluated effectiveness of regular exercise alone, regular exercise plus healthy eating, and…

  1. Phonologic Abilities of a Preschool Child with Prader-Willi Syndrome.

    Science.gov (United States)

    Dyson, Alice T.; Lombardino, Linda J.

    1989-01-01

    A case study follows the development of phonologic abilities in a child with Prader-Willi syndrome, during her enrollment in language and phonologic remediation from age 2:7 to 6:1. Changes in her phonetic inventory, in the set of phonemes used correctly, and in phonologic processes are described. (Author/JDD)

  2. Management of Speech and Language Impairment in a Case of Prader-Willi Syndrome.

    Science.gov (United States)

    Edmonston, Nellie K.

    1982-01-01

    The case report describes the speech and language charactersitics of a five-year-old girl with Prader-Willi syndrome, a congential disorder (characterized by mental retardation and specific physical characteristics), and the language therapy procedures used over a 10-month period. (Author/SW)

  3. Maladaptive Behavior Differences in Prader-Willi Syndrome Due to Paternal Deletion versus Maternal Uniparental Disomy.

    Science.gov (United States)

    Dykens, Elisabeth M.; King, Bryan H.; Cassidy, Suzanne B.

    1999-01-01

    This study compared maladaptive behavior in 23 people with Prader-Willi syndrome due to paternal deletion and in 23 age- and gender-matched subjects with maternal uniparental disomy. Controlling for IQs, the deletion cases showed significantly higher maladaptive ratings, more symptom-related distress, and more behavior problems. Findings suggest a…

  4. Prader-Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene

    Directory of Open Access Journals (Sweden)

    Michael D. Fountain

    2016-01-01

    Full Text Available Prader-Willi syndrome (PWS is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately 25% meet criteria for autism spectrum disorder (ASD. PWS is caused by the absence of paternally expressed, maternally silenced genes at chromosome 15q11-q13. MAGEL2 is one of five protein-coding genes in the PWS-critical domain. Truncating point mutations of the paternal allele of MAGEL2 cause Schaaf-Yang syndrome, which has significant phenotypic overlap with PWS, but is also clinically distinct; based on the presence of joint contractures, and a particularly high prevalence of autism spectrum disorder (up to 75% of affected individuals. The clinical and molecular overlap between PWS and Schaaf-Yang syndrome, but also their distinguishing features provide insight into the pathogenetic mechanisms underlying both disorders.

  5. Prevalence and Phenotype of Sleep Disorders in 60 Adults With Prader-Willi Syndrome.

    Science.gov (United States)

    Ghergan, Adelina; Coupaye, Muriel; Leu-Semenescu, Smaranda; Attali, Valérie; Oppert, Jean-Michel; Arnulf, Isabelle; Poitou, Christine; Redolfi, Stefania

    2017-12-01

    Excessive sleepiness is a common symptom in Prader-Willi syndrome (PWS), and it negatively impacts the quality of life. Obstructive sleep apnea and narcolepsy phenotypes have been reported in PWS. We characterized sleep disorders in a large cohort of adults with PWS. All consecutive patients with genetically confirmed PWS unselected for sleep-related symptoms, underwent a clinical interview, polysomnography, and multiple sleep latency tests (MSLT, n = 60), followed by long-term (24 hours) polysomnography (n = 22/60). Among 60 adults evaluated (57% female, aged 25 ± 10 years, body mass index: 39 ± 12 kg/m2), 67% reported excessive sleepiness. According to the sleep study results, 43% had a previously unrecognized hypersomnia disorder, 15% had an isolated sleep breathing disorder, 12% had combined hypersomnia disorder and untreated breathing sleep disorder, and only 30% had normal sleep. Isolated hypersomnia disorder included narcolepsy in 35% (type 1, n = 1, and type 2, n = 8), hypersomnia in 12% (total sleep time >11 hours, n = 2, and MSLT sleep onset in REM periods and MSLT >8 minutes, n = 10, and 8 minutes Sleep breathing disorders, isolated and combined, included obstructive sleep apnea (n = 14, already treated in seven), sleep hypoxemia (n = 1) and previously undiagnosed hypoventilation (n = 5). Modafinil was taken by 16 patients (well tolerated in 10), resulting in improved sleepiness over a mean 5-year follow-up period. Sleepiness affects more than half of adult patients with PWS, with a variety of hypersomnia disorder (narcolepsy, hypersomnia, and borderline phenotypes) and breathing sleep disorders. Earlier diagnosis and management of sleep disorders may improve sleepiness, cognition, and behavior in these patients. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com

  6. Investigating Autism-Related Symptoms in Children with Prader-Willi Syndrome: A Case Study

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    Jeffrey A. Bennett

    2017-02-01

    Full Text Available Prader-Willi syndrome (PWS, a rare genetic disorder caused by the lack of expression of paternal genes from chromosome 15q11-13, has been investigated for autism spectrum disorder (ASD symptomatology in various studies. However, previous findings have been variable, and no studies investigating ASD symptomatology in PWS have exclusively studied children. We aimed to characterize social communication functioning and other ASD-related symptoms in children with PWS, and assessed agreement across measures and rates of ASD diagnosis. Measures included the Autism Diagnostic Observation Schedule-2 (ADOS-2, the Social Communication Questionnaire (SCQ, Social Responsiveness Scale-2 (SRS-2, Social Skills Improvement System-Rating Scales (SSIS-RS, and the Vineland Adaptive Behavioral Scales-II (VABS-II. General adaptive and intellectual skills were also assessed. Clinical best estimate (CBE diagnosis was determined by an experienced developmental pediatrician, based on history and review of all available study measures, and taking into account overall developmental level. Participants included 10 children with PWS, aged 3 to 12 years. Three of the 10 children were male and genetic subtypes were two deletion (DEL and eight uniparental disomy (UPD (with a total of 6 female UPD cases. Although 8 of the 10 children exceeded cut-offs on at least one of the ASD assessments, agreement between parent questionnaires (SCQ, SRS-2, SSIS-RS and observational assessment (ADOS-2 was very poor. None of the children were assigned a CBE diagnosis of ASD, with the caveat that the risk may have been lower because of the predominance of girls in the sample. The lack of agreement between the assessments emphasizes the complexity of interpreting ASD symptom measures in children with PWS.

  7. Investigating Autism-Related Symptoms in Children with Prader-Willi Syndrome: A Case Study.

    Science.gov (United States)

    Bennett, Jeffrey A; Hodgetts, Sandra; Mackenzie, Michelle L; Haqq, Andrea M; Zwaigenbaum, Lonnie

    2017-02-28

    Prader-Willi syndrome (PWS), a rare genetic disorder caused by the lack of expression of paternal genes from chromosome 15q11-13, has been investigated for autism spectrum disorder (ASD) symptomatology in various studies. However, previous findings have been variable, and no studies investigating ASD symptomatology in PWS have exclusively studied children. We aimed to characterize social communication functioning and other ASD-related symptoms in children with PWS, and assessed agreement across measures and rates of ASD diagnosis. Measures included the Autism Diagnostic Observation Schedule-2 (ADOS-2), the Social Communication Questionnaire (SCQ), Social Responsiveness Scale-2 (SRS-2), Social Skills Improvement System-Rating Scales (SSIS-RS), and the Vineland Adaptive Behavioral Scales-II (VABS-II). General adaptive and intellectual skills were also assessed. Clinical best estimate (CBE) diagnosis was determined by an experienced developmental pediatrician, based on history and review of all available study measures, and taking into account overall developmental level. Participants included 10 children with PWS, aged 3 to 12 years. Three of the 10 children were male and genetic subtypes were two deletion (DEL) and eight uniparental disomy (UPD) (with a total of 6 female UPD cases). Although 8 of the 10 children exceeded cut-offs on at least one of the ASD assessments, agreement between parent questionnaires (SCQ, SRS-2, SSIS-RS) and observational assessment (ADOS-2) was very poor. None of the children were assigned a CBE diagnosis of ASD, with the caveat that the risk may have been lower because of the predominance of girls in the sample. The lack of agreement between the assessments emphasizes the complexity of interpreting ASD symptom measures in children with PWS.

  8. Irisin and the Metabolic Phenotype of Adults with Prader-Willi Syndrome.

    Directory of Open Access Journals (Sweden)

    Harry J Hirsch

    Full Text Available Hyperphagia, low resting energy expenditure, and abnormal body composition contribute to severe obesity in Prader Willi syndrome (PWS. Irisin, a circulating myokine, stimulates "browning" of white adipose tissue resulting in increased energy expenditure and improved insulin sensitivity. Irisin has not been previously studied in PWS.Compare plasma and salivary irisin in PWS adults and normal controls. Examine the relationship of irisin to insulin sensitivity and plasma lipids.A fasting blood sample for glucose, lipids, insulin, leptin, adinopectin, and irisin was obtained from 22 PWS adults and 54 healthy BMI-matched volunteers. Saliva was collected for irisin assay in PWS and controls.Fasting glucose (77 ± 9 vs 83 ± 7 mg/dl, p = 0.004, insulin (4.1 ± 2.0 vs 7.9 ± 4.7 μU/ml, p<0.001, and triglycerides (74 ± 34 vs 109 ± 71 mg/dl, p = 0.007 were lower in PWS than in controls. Insulin resistance (HOMA-IR was lower (0.79 ± 0.041 vs 1.63 ± 1.02, p<0.001 and insulin sensitivity (QUICKI was higher (0.41 ± 0.04 vs 0.36 ± 0.03, p<0.001 in PWS. Plasma irisin was similar in both groups, but salivary irisin (64.5 ± 52.0 vs 33.0 ± 12.1ng/ml, plasma leptin (33.5 ± 24.2 vs 19.7 ± 19.3 ng/ml and plasma adinopectin (13.0 ± 10.8 vs 7.6 ± 4.5μg/ml were significantly greater in PWS (p<0.001. In PWS, plasma irisin showed positive Pearson correlations with total cholesterol (r = 0.58, p = 0.005, LDL-cholesterol (r = 0.59, p = 0.004, and leptin (r = 0.43, p = 0.045. Salivary irisin correlated negatively with HDL-cholesterol (r = -0.50, p = 0.043 and positively with LDL-cholesterol (r = 0.51, p = 0.037 and triglycerides (r = 0.50, p = 0.041.Salivary irisin was markedly elevated in PWS although plasma irisin was similar to levels in controls. Significant associations with plasma lipids suggest that irisin may contribute to the metabolic phenotype of PWS.

  9. Gender Differences in the Behavioral Symptom Severity of Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Masao Gito

    2015-01-01

    Full Text Available Objectives. This study measured gender differences in Prader-Willi syndrome (PWS in regard to the severity of behavioral symptoms. Methods. The Food Related Problem Questionnaire (FRPQ, the Aberrant Behavior Checklist Japanese Version, the Childhood Routines Inventory, the Pervasive Developmental Disorders Autism Society Japan Rating Scale, and Japanese ADHD-RS were administered to PWS patients (45 males aged 6 to 58 and 37 females aged 6 to 45. To examine the effects that gender and genotype have on the severity of each symptom, two-way ANOVAs were conducted. Results. Significant interactions were found only in regard to FRPQ scores, such as FRPQ total score (F(1, 78 = 8.43, p<0.01. The FRPQ of male deletion (DEL individuals was higher than that of female DEL and male mUPD. The FRPQ of male maternal uniparental disomy (mUPD was lower than that of female mUPD. Conclusions. In terms of problem behaviors, routines, autistic behaviors, and hyperactivity, no significant differences were found. Food-related behaviors in DEL were more severe in males, although those in mUPD were less severe in males.

  10. A review of chemosensory perceptions, food preferences and food-related behaviours in subjects with Prader-Willi Syndrome.

    Science.gov (United States)

    Martínez Michel, Lorelei; Haqq, Andrea M; Wismer, Wendy V

    2016-04-01

    Hyperphagia and obsessive preoccupation with food are hallmark characteristics of Prader-Willi Syndrome (PWS). Although hyperphagia in PWS is linked to hypothalamic dysfunction, the underlying mechanisms behind this problem are poorly understood. Moreover, our understanding of how chemosensory perceptions and food choice/preferences relate to hyperphagia in individuals with PWS is very limited. This narrative review synthesizes studies that assessed chemosensory perceptions, food choices and food-related behaviours in PWS individuals and highlights knowledge gaps in research for further exploration. Twenty seven publications from relevant databases met inclusion criteria and were organized thematically by study technique in the review. Results suggested that PWS individuals have consistent preferences for sweet tastes and in most studies have exhibited a preference for calorie-dense foods over lower calorie foods. No firm conclusions were drawn concerning the chemosensory perceptions of PWS individuals and their influence on food preferences or choices; chemosensation among PWS individuals is an understudied topic. Current evidence suggests that eating behaviour in PWS is a complex phenomenon that involves a dysfunctional satiation and not excessive hunger. Food preferences, choices, and related behaviours and the impact of these on obesity management in those with PWS remain poorly understood and require further study using validated tools and methodologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Nutritional intervention with hypocaloric diet for weight control in children and adolescents with Prader-Willi Syndrome.

    Science.gov (United States)

    Lima, Vivian Penner de; Emerich, Deisy Ribas; Mesquita, Maria Luiza Guedes de; Paternez, Ana Carolina Almada Colucci; Carreiro, Luiz Renato Rodrigues; Pina Neto, João Monteiro de; Teixeira, Maria Cristina Triguero Veloz

    2016-04-01

    Prader-Willi Syndrome (PWS) is a genetic disorder caused by the lack of expression of paternal alleles in the proximal region of the long arm of chromosome 15. Low inhibitory control and hyperphagia are two of the most severe neurobehavioral symptoms of the syndrome. The aim of the present study was to assess the efficiency of nutritional training program with the use hypocaloric diet for weight control in a group of five children and adolescents with PWS. The intervention program consisted of 10 sessions for parents' orientation during 8months. Patients had their anthropometric measures assessed (weight, height and body mass index - BMI). The main results indicate weight maintenance, height increase, and BMI decrease after intervention. These results were considered indicators of the program's efficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus.

    Directory of Open Access Journals (Sweden)

    Emily Y Smith

    2011-12-01

    Full Text Available The Prader-Willi syndrome (PWS [MIM 17620] and Angelman syndrome (AS [MIM 105830] locus is controlled by a bipartite imprinting center (IC consisting of the PWS-IC and the AS-IC. The most widely accepted model of IC function proposes that the PWS-IC activates gene expression from the paternal allele, while the AS-IC acts to epigenetically inactivate the PWS-IC on the maternal allele, thus silencing the paternally expressed genes. Gene order and imprinting patterns at the PWS/AS locus are well conserved from human to mouse; however, a murine AS-IC has yet to be identified. We investigated a potential regulatory role for transcription from the Snrpn alternative upstream exons in silencing the maternal allele using a murine transgene containing Snrpn and three upstream exons. This transgene displayed appropriate imprinted expression and epigenetic marks, demonstrating the presence of a functional AS-IC. Transcription of the upstream exons from the endogenous locus correlates with imprint establishment in oocytes, and this upstream exon expression pattern was conserved on the transgene. A transgene bearing targeted deletions of each of the three upstream exons exhibited loss of imprinting upon maternal transmission. These results support a model in which transcription from the Snrpn upstream exons directs the maternal imprint at the PWS-IC.

  13. Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation

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    Saitoh, S.; Cassidy, S.B.; Conroy, J.M. [Univ. of Hospitals of Cleveland, OH (United States)] [and others

    1997-01-20

    Recent studies have identified a new class of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients who have biparental inheritance, but neither the typical deletion nor uniparental disomy (UPD) or translocation. However, these patients have uniparental DNA methylation throughout 15q11-q13, and thus appear to have a mutation in the imprinting process for this region. Here we describe detailed clinical findings of five AS imprinting mutation patients (three families) and two PWS imprinting mutation patients (one new family). All these patients have essentially the classical clinical phenotype for the respective syndrome, except that the incidence of microcephaly is lower in imprinting mutation AS patients than in deletion AS patients. Furthermore, imprinting mutation AS and PWS patients do not typically have hypopigmentation, which is commonly found in patients with the usual large deletion. Molecular diagnosis of these cases is initially achieved by DNA methylation analyses of the DN34/ZNF127, PW71 (D15S63), and SNRPN loci. The latter two probes have clear advantages in the simple molecular diagnostic analysis of PWS and AS patients with an imprinting mutation, as has been found for typical deletion or UPD PWS and AS cases. With the recent finding of inherited microdeletions in PWS and AS imprinting mutation families, our studies define a new class of these two syndromes. The clinical and molecular identification of these PWS and AS patients has important genetic counseling consequences. 49 refs., 4 figs., 3 tabs.

  14. Periodontal disease in a patient with Prader-Willi syndrome: a case report

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    Kitamura Masahiro

    2011-07-01

    Full Text Available Abstract Introduction Prader-Willi syndrome is a complex genetic disease caused by lack of expression of paternally inherited genes on chromosome 15q11-q13. The prevalence of Prader-Willi syndrome is estimated to be one in 10,000 to 25,000. However, descriptions of the oral and dental phenotype are rare. Case presentation We describe the clinical presentation and periodontal findings in a 20-year-old Japanese man with previously diagnosed Prader-Willi syndrome. Clinical and radiographic findings confirmed the diagnosis of periodontitis. The most striking oral findings were anterior open bite, and crowding and attrition of the lower first molars. Periodontal treatment consisted of tooth-brushing instruction and scaling. Home care involved recommended use of adjunctive chlorhexidine gel for tooth brushing twice a week and chlorhexidine mouthwash twice daily. Gingival swelling improved, but further treatment will be required and our patient's oral hygiene remains poor. The present treatment of tooth-brushing instruction and scaling every three weeks therefore only represents a temporary solution. Conclusions Rather than being a direct result of genetic defects, periodontal diseases in Prader-Willi syndrome may largely result from a loss of cuspid guidance leading to traumatic occlusion, which in turn leads to the development of periodontal diseases and dental plaque because of poor oral hygiene. These could be avoided by early interventions to improve occlusion and regular follow-up to monitor oral hygiene. This report emphasizes the importance of long-term follow-up of oral health care by dental practitioners, especially pediatric dentists, to prevent periodontal disease and dental caries in patients with Prader-Willi syndrome, who appear to have problems maintaining their own oral health.

  15. Periodontal disease in a patient with Prader-Willi syndrome: a case report.

    Science.gov (United States)

    Yanagita, Manabu; Hirano, Hiroyuki; Kobashi, Mariko; Nozaki, Takenori; Yamada, Satoru; Kitamura, Masahiro; Murakami, Shinya

    2011-07-28

    Prader-Willi syndrome is a complex genetic disease caused by lack of expression of paternally inherited genes on chromosome 15q11-q13. The prevalence of Prader-Willi syndrome is estimated to be one in 10,000 to 25,000. However, descriptions of the oral and dental phenotype are rare. We describe the clinical presentation and periodontal findings in a 20-year-old Japanese man with previously diagnosed Prader-Willi syndrome. Clinical and radiographic findings confirmed the diagnosis of periodontitis. The most striking oral findings were anterior open bite, and crowding and attrition of the lower first molars. Periodontal treatment consisted of tooth-brushing instruction and scaling. Home care involved recommended use of adjunctive chlorhexidine gel for tooth brushing twice a week and chlorhexidine mouthwash twice daily. Gingival swelling improved, but further treatment will be required and our patient's oral hygiene remains poor. The present treatment of tooth-brushing instruction and scaling every three weeks therefore only represents a temporary solution. Rather than being a direct result of genetic defects, periodontal diseases in Prader-Willi syndrome may largely result from a loss of cuspid guidance leading to traumatic occlusion, which in turn leads to the development of periodontal diseases and dental plaque because of poor oral hygiene. These could be avoided by early interventions to improve occlusion and regular follow-up to monitor oral hygiene. This report emphasizes the importance of long-term follow-up of oral health care by dental practitioners, especially pediatric dentists, to prevent periodontal disease and dental caries in patients with Prader-Willi syndrome, who appear to have problems maintaining their own oral health.

  16. Multidisciplinary care in the intensive care unit for a patient with Prader-Willi syndrome: a dental approach.

    Science.gov (United States)

    Setti, Juliana Santiago; Pinto, Sérgio Felix; Gaetti-Jardim, Ellen Cristina; Manrique, Gustavo Rodrigues; Mendonça, José Carlos Garcia de

    2012-03-01

    Prader-Willi syndrome is a genetic neurobehavioral disease affecting children's development and resulting in obesity, reduced height, hypotonia, endocrine disorders and cognitive deficits, which may impair oral integrity. This study aims to report on a case involving a white male 15-year-old patient with Prader-Willi syndrome whose oral examination revealed bacterial plaque, gingivitis, poor occlusion, viscous salivation and multiple lip, jugal mucosa, inserted gum and tongue ulcerations. An excision biopsy revealed oral ulcerations typical of herpes, which were considered to be likely to correlate with herpes encephalitis. This result demonstrates that a large portion of the deleterious effects of Prader-Willi syndrome can be attenuated by appropriate diagnosis and early therapeutic intervention, highlighting the role of an integrated multidisciplinary team in the development of therapeutic protocols for Prader-Willi syndrome patients.

  17. Antioxidant Effects of Potassium Ascorbate with Ribose Therapy in a Case with Prader Willi Syndrome

    Directory of Open Access Journals (Sweden)

    C. Anichini

    2012-01-01

    Full Text Available Oxidative stress (OS is involved in several human diseases, including obesity, diabetes, atherosclerosis, carcinogenesis, as well as genetic diseases. We previously found that OS occurs in Down Syndrome as well as in Beckwith-Wiedemann Syndrome (BWS. Here we describe the clinical case of a female patient with Prader Willi Syndrome (PWS, a genomic imprinting disorder, characterized by obesity, atherosclerosis and diabetes mellitus type 2, pathologies in which a continuous and important production of free radicals takes place. We verified the presence of OS by measuring a redox biomarkers profile including total hydroperoxides (TH, non protein-bound iron (NPBI, thiols (SH, advanced oxidation protein products (AOPP and isoprostanes (IPs. Thus we introduced in therapy an antioxidant agent, namely potassium ascorbate with ribose (PAR, in addition to GH therapy and we monitored the redox biomarkers profile for four years. A progressive decrease in OS biomarkers occurred until their normalization. In the meantime a weight loss was observed together with a steady growth in standards for age and sex.

  18. Experience of severe desaturation during anesthetic induction period in an obese adult patient with Prader-Willi syndrome -A case report-.

    Science.gov (United States)

    Choi, Joon Woo; Kim, Eun-Ju; Min, Byung Woo; Ban, Jong Seouk; Lee, Sang Gon; Lee, Ji-Hyang

    2012-02-01

    Prader-Willi syndrome is characterized by infantile hypotonia, childhood-onset obesity, short stature, mental retardation, hyperphagia, hypogonadism. After infantile hypotonia phase, patient is prone to morbid obesity due to hyperphagia. Complications associated with morbid obesity are recognized as the main risk factors for death the lifespan of patients with Prader-Willi syndrome. We experienced desaturation and bronchospasm during arteriovenous fistula surgery in an obese adult with Prader-Willi syndrome.

  19. Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome.

    Science.gov (United States)

    Lukoshe, Akvile; van Dijk, Suzanne E; van den Bosch, Gerbrich E; van der Lugt, Aad; White, Tonya; Hokken-Koelega, Anita C

    2017-01-01

    Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional connectivity with other brain regions. Thus, the aim of this study was to examine the anatomical differences of the hypothalamus, mammillary bodies, and pituitary gland as well as resting state functional connectivity of the hypothalamus in children with PWS. Twenty-seven children with PWS (13 DEL, 14 mUPD) and 28 typically developing children were included. Manual segmentations by a blinded investigator were performed to determine the volumes of the hypothalamus, mammillary bodies, and pituitary gland. In addition, brain-wide functional connectivity analysis was performed using the obtained masks of the hypothalamus. Children with PWS showed altered resting state functional connectivity between hypothalamus and right and left lateral occipital complex, compared to healthy controls. In addition, children with PWS had on average a 50% smaller pituitary volume, an irregular shape of the pituitary, and a longer pituitary stalk. Pituitary volume did not increase in volume during puberty in PWS. No volumetric differences in the hypothalamus and mammillary bodies were found. In all subjects, the posterior pituitary bright spot was observed. We report altered functional hypothalamic connectivity with lateral occipital complexes in both hemispheres, which are implicated in response to food and reward system, and absence of connectivity might therefore at least partially contribute to the preoccupation with food in PWS.

  20. The Developmental Trajectory of Self-Injurious Behaviours in Individuals with Prader Willi Syndrome, Autism Spectrum Disorder and Intellectual Disability

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    Lauren J. Rice

    2016-02-01

    Full Text Available In the present study we examined the nature and developmental trajectory of self-injurious behaviour in Prader Willi syndrome (PWS and autism spectrum disorder (ASD. The development of interventions is greatly aided by understanding gene to behaviour pathways, and this requires an accurate description of the behaviour phenotype, that is, which types and natural history of self-injurious behaviour are more common in PWS and ASD and which are shared with other forms of developmental disability. Self-injury displayed by individuals with PWS and individuals with ASD was compared with that reported in a group of individuals with intellectual disability due to mixed aetiology (ID group. Three self-injurious behaviours (head banging, skin-picking and hitting and/or biting self were measured on five occasions over 18 years using the Developmental Behaviour Checklist (DBC a well-validated caregiver report measure. Rates of skin picking were higher in individuals with PWS and hitting and/or biting self was higher in individuals with ASD compared to the ID group. Rates of head banging were similar across the three groups. Over time, skin-picking and head banging increased with age for individuals with ASD and hitting and/or biting self increased for the PWS group. In the PWS and mixed ID groups head banging decreased with age. These findings suggest that the typology and developmental trajectories of self-injurious behaviours differ between those with PWS and ASD.

  1. Transcranial direct current stimulation reduces food-craving and measures of hyperphagia behavior in participants with Prader-Willi syndrome.

    Science.gov (United States)

    Bravo, Gabriela L; Poje, Albert B; Perissinotti, Iago; Marcondes, Bianca F; Villamar, Mauricio F; Manzardo, Ann M; Luque, Laura; LePage, Jean F; Stafford, Diane; Fregni, Felipe; Butler, Merlin G

    2016-03-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by intellectual disabilities and insatiable appetite with compulsive eating leading to severe obesity with detrimental health consequences. Transcranial direct current stimulation (tDCS) has been shown to modulate decision-making and cue-induced food craving in healthy adults. We conducted a pilot double blind, sham-controlled, multicenter study of tDCS modulation of food drive and craving in 10 adult PWS participants, 11 adult obese (OB) and 11 adult healthy-weight control (HWC) subjects. PWS and OB subjects received five consecutive daily sessions of active or sham tDCS over the right dorsolateral prefrontal cortex (DLPFC), while HWC received a single sham and active tDCS in a crossover design. Standardized psychometric instruments assessed food craving, drive and hyperphagia by self-report and caregiver assessment over 30 days. Robust baseline differences were observed in severity scores for the Three-Factor Eating Questionnaire (TFEQ) and Dykens Hyperphagia Questionnaire (DHQ) for PWS compared to HWC while obese participants were more similar to HWC. Active tDCS stimulation in PWS was associated with a significant change from baseline in TFEQ Disinhibition (Factor II) (Ƶ = 1.9, P food drive and behaviors impacting hyperphagia in PWS. Transcranial direct current stimulation may represent a straight-forward, low risk and low cost method to improve care, management and quality of life in PWS. © 2015 Wiley Periodicals, Inc.

  2. Reduced cortical complexity in children with Prader-Willi Syndrome and its association with cognitive impairment and developmental delay.

    Science.gov (United States)

    Lukoshe, Akvile; Hokken-Koelega, Anita C; van der Lugt, Aad; White, Tonya

    2014-01-01

    Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in

  3. Reduced cortical complexity in children with Prader-Willi Syndrome and its association with cognitive impairment and developmental delay.

    Directory of Open Access Journals (Sweden)

    Akvile Lukoshe

    Full Text Available BACKGROUND: Prader-Willi Syndrome (PWS is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. METHODS: High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL, 12 with maternal uniparental disomy (mUPD and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI was obtained using the FreeSurfer software suite. RESULTS: Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. CONCLUSIONS: These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to

  4. Parent training education program: a pilot study, involving families of children with Prader-Willi syndrome.

    Science.gov (United States)

    Kodra, Yllka; Kondili, Loreta A; Ferraroni, Alessia; Serra, Maria Antonietta; Caretto, Flavia; Ricci, Maria Antonietta; Taruscio, Domenica

    2016-01-01

    Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by severe hypotonia during the neonatal period and the first two years of life, the onset of hyperphagia with a risk of obesity during infancy and adulthood, learning difficulties and behavioral or severe psychiatric problems. This complex disease has severe consequences and difficult management issues also for patients' families. Parents of children with PWS need appropriate psychoeducational intervention in order to better manage their children with PWS. The purpose of this study was the implementation and evaluation of a PWS psychoeducational parent training program. The Italian National Center for Rare Diseases implemented a pilot parent training program offered to parents of children with PWS. The intervention's effects was evaluated using questionnaires comprised of 11 items rated on a 7 point Likert scale. The intervention was offered to 43 parents. The behavior problems management, dietary restrictions, autonomy and relationships were indicated by parents as the priority topics which needed to be addressed. Evaluations, immediately post-intervention and after 6 months, were reported by parents, fulfilling specific questionnaires. 90% of parents involved in the study, appreciated the methodology, 86% felt more informed about PWS, 47-62% felt more capable to better approach behaviour's problems, 20-25% felt better about the child's health situation and future expectations. Feeling more capable to help the child autonomy and relationships were reported in 62% and 63% of parents respectively, which decreased significantly (p < 0.05) according to the evaluation 6 months after the intervention. Younger age of parents (< 44 years of age) was significantly correlated with better understanding on how to help the child's autonomy (OR: 0.05; CI: 0.04-0.8) and to better collaborate with the child's teachers (OR: 0.02; CI: 0.001-0.9). Parent training is a promising intervention for parents of children

  5. Molecular diagnosis of Prader-Willi syndrome: Parent-of-origin dependent methylation sites and non-isotopic detection of (CA){sub n} dinucleotide repeat polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Lerer, I.; Meiner, V.; Pashut-Lavon, I.; Abeliovich, D.

    1994-08-01

    We describe our experience in the molecular diagnosis of 22 patients suspected of Prader-Willi syndrome (PWS) using a DNA probe PW71 (D15S63) which detects a parent-of-origin specific methylated site in the PWS critical region. The cause of the syndrome was determined as deletion or uniparental disomy according to the segregation of (CA){sub n} dinucleotide repeat polymorphisms of the PWS/AS region and more distal markers of chromosome 15. In 10 patients the clinical diagnosis was confirmed by the segregation of (CA){sub n}, probably due to paternal microdeletion in the PWs critical region which did not include the loci D15S97, D15S113, GABRB3, and GABRA5. This case demonstrates the advantage of the DNA probe PW71 in the diagnosis of PWS. 31 refs., 2 figs., 3 tabs.

  6. Serum adiponectin levels in adults with Prader-Willi syndrome are independent of anthropometrical parameters and do not change with GH treatment

    DEFF Research Database (Denmark)

    Hoybye, Charlotte; Bruun, Jens M; Richelsen, Bjorn

    2004-01-01

    it of interest to measure adiponectin levels in PWS. PATIENTS AND METHODS: 17 adults, nine men and eight women, 17 to 32 years of age, with a mean body mass index (BMI) of 35+/-3.2 kg/m2 participated. All had clinical PWS. They were randomized to treatment with placebo or GH (Genotropin) for six months......OBJECTIVE: Obesity and growth hormone (GH) deficiency are common in Prader-Willi syndrome (PWS) and these patients are at risk of metabolic diseases in adult life and of reduced life span. Low adiponectin values are associated with obesity and the metabolic syndrome. We therefore found......, and subsequently all received GH for 12 months. At baseline, serum total adiponectin levels in the PWS patients were compared with 25 lean and 34 obese controls. Body composition and various metabolic parameters, including adiponectin, were studied every six months in the PWS group. RESULTS: Serum adiponectin...

  7. Growth hormone receptor (GHR) gene polymorphism and scoliosis in Prader-Willi syndrome.

    Science.gov (United States)

    Butler, Merlin G; Hossain, Waheeda; Hassan, Maaz; Manzardo, Ann M

    2018-04-01

    A growth hormone receptor (GHR) gene polymorphism impacts sensitivity to endogenous and exogenous growth hormone (GH) to moderate growth and development. Increased sensitivity may accelerate spinal growth and contribute to scoliosis, particularly in GH-deficient and treated populations such as Prader-Willi syndrome (PWS). Therefore, we examined the relationship between GHR genotype and scoliosis (case and control) in PWS cohorts. We utilized a case-control design in a study of 73 subjects (34M; 39F) with genetically confirmed PWS in 32 individuals previously diagnosed with moderate to severe scoliosis (mean age=16.9±10.2years; age range of 1 to 41years) and 41 adults with no evidence of scoliosis (mean age=30.8±9.7years; age range of 18 to 56years). The GHR gene polymorphism was determined using PCR specific primers to capture the two recognized GHR gene fragment sizes [i.e., full length (fl) or exon 3 deletions (d3)]. Twenty-three (72%) of the 32 case subjects with scoliosis required surgical correction with an approximately equal balance for gender and PWS genetic subtype among cases and 41 control subjects without scoliosis. The GHR d3/d3 genotype was identified in N=2 of 8 (25%) cases with scoliosis and the d3/fl genotype was identified in N=11 of 25 (44%) cases with scoliosis but the distribution difference did not statistically differ. The GHR fl/fl genotype was correlated with a significantly faster rate and heavier weight gain among case subjects. Our examination of demographic and genetic markers associated with scoliosis and surgical repair in PWS found no evidence to support differences in gender, PWS genetic subtype or GHR d3 allele distributions among the case vs control groups. Those with fl/fl alleles were heavier than those with d3/d3 or d3/fl genotypes and warrant further study with a larger sample size and possibly to include other vulnerable populations requiring growth hormone treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. [Multiorgan failure associated with hyperthermia in an infant with Prader-Willi syndrome. case report].

    Science.gov (United States)

    Donoso, Alejandro; Arriagada, Daniela; Campbell, Stephanie; Cruces, Pablo

    2013-10-01

    Heat stroke is a medical emergency characterized primarily by an elevated core temperature associated with a systemic inflammatory response, which causes multiple organ dysfunction in which encephalopathy predominates. If it is not early treated has high mortality. The Prader-Willi syndrome is a multisystem genetic disorder secondary to an abnormality in long arm chromosome 15 (15q11-q13), characterized by neonatal central hypotonia, developmental delay, hypogonadism, hyperphagia and obesity. These patients are susceptible to developing thermoregulatory problems. We report the case of a 5-month-old infant, in whom a diagnosis of Prader-Willi syndrome was established in the course of a febrile episode without known focus, who developed multiorganic failure and rhabdomyolysis secondary to hyperthermia.

  9. Psychomotor development in infants with Prader-Willi syndrome and associations with sleep-related breathing disorders.

    Science.gov (United States)

    Festen, Dederieke A M; Wevers, Maaike; de Weerd, Al W; van den Bossche, Renilde A S; Duivenvoorden, Hugo J; Otten, Barto J; Wit, Jan Maarten; Hokken-Koelega, Anita C S

    2007-08-01

    Prader-Willi syndrome (PWS) is a neurogenetic disorder with hypotonia, psychomotor delay, obesity, short stature, and sleep-related breathing disorders. The aim of this study was to evaluate the association between psychomotor development and sleep-related breathing disorders in PWS infants. Bayley Scales of Infant Development were performed in 22 PWS infants, with a median (interquartile range, IQR) age of 1.8 (1.1-3.4) y, and a body mass index SD score (BMISDS) of -0.5 (-1.3 to 1.6). We evaluated psychomotor development in relation to results of polysomnography. Median (IQR) mental and motor development was 73.1% (64.3-79.6%) and 55.2% (46.5-63.1%) of normal children, respectively. All infants had sleep-related breathing disorders, mostly of central origin. The apnea hypopnea index was not associated with psychomotor development. Only four infants had obstructive sleep apnea syndrome (OSAS). They had a significantly delayed mental development of 65.5% (60.0-70.3%) of normal. They had a median BMISDS of 1.4 (0.1-1.6), which tended to be higher than in those without OSAS. Our data indicate that psychomotor development in PWS infants is not related to central sleep-related breathing disorders, but infants with OSAS have more severely delayed mental development, suggesting that PWS infants should be screened for OSAS.

  10. Intraoperative Adrenal Insufficiency in a Patient with Prader-Willi Syndrome

    OpenAIRE

    Barbara, David W.; Hannon, James D.; Hartman, William R.

    2012-01-01

    Prader-Willi syndrome (PW) is a rare genetic disorder with multi-organ system involvement. These patients present many perioperative challenges including sleep-related breathing disorders, morbid obesity, thick salivary secretions, mental retardation, and difficult intravenous access. PW has been suggested to be associated with central adrenal insufficiency. We report a novel case of persistent severe hypotension from previously undiagnosed and asymptomatic adrenal insufficiency in a pediatri...

  11. Biofeedback therapy for chronic constipation in a patient with Prader-Willi syndrome.

    Science.gov (United States)

    Corral, Juan E; Kataria, Rahul; Vickers, Dawn; Koutouby, Raghad; Moshiree, Baharak

    2015-01-01

    Constipation is a common feature of Prader-Willi syndrome. Research exploring the prevalence, cause and treatment options for constipation is limited and lacks objective measurements such as anorectal manometry. We report a case of a 16-year-old lady with Prader-Willi syndrome presenting with rectal pain and constipation for 2 years despite multiple medications and weekly enemas. She also noted passive fecal incontinence that required frequent manual disimpactions. Anorectal manometry revealed an abnormal relaxation of the puborectalis and external sphincter muscles on push maneuvers suggesting dyssynergic defecation and rectal hypersensitivity. Contraction and relaxation of her pelvic muscles were recorded with electromyography. Relaxation of the puborectalis muscle improved significantly after three biofeedback sessions. Patient was successfully tapered off laxatives and has been maintained on linaclotide only. Dyssynergic defecation may be a common finding in Prader-Willi syndrome. In selected cases we recommend anorectal manometry to identify neuromuscular dysfunction and subsequent biofeedback therapy depending on the degree of mental retardation to minimize overuse of laxatives.

  12. Prader-Willi syndrome, excessive daytime sleepiness, and narcoleptic symptoms: a case report.

    Science.gov (United States)

    Weselake, Sara V; Foulds, Jessica L; Couch, Robert; Witmans, Manisha B; Rubin, Daniela; Haqq, Andrea M

    2014-04-17

    Sleep abnormalities, including narcolepsy and cataplexy, are a common feature of Prader-Willi syndrome. Long-term treatment with the central nervous system stimulant modafinil has not been reported. In this case report we present a longitudinal perspective of sleep abnormalities in a nine-year-old Caucasian girl with Prader-Willi syndrome from age two to age nine, and detail the response to treatment with the central nervous system stimulant modafinil. Our patient presented at two years of age with hypersomnia and narcoleptic episodes with cataplectic features. Initial polysomnograph testing revealed adequate sleep efficiency, but increased sleep fragmentation especially during rapid eye movement sleep. The narcoleptic episodes continued and a repeat polysomnograph at age five years confirmed features consistent with narcolepsy. Further sleep studies at six years, including a multiple sleep latency test, demonstrated signs of excessive daytime sleepiness. Treatment with modafinil was initiated at age seven years six months due to persistent hypersomnia and narcoleptic symptoms. Two polysomnograph studies were performed following treatment with modafinil, at age eight years six months and nine years three months. These studies showed excellent sleep efficiency and improvement of rapid eye movement sleep parameters, supporting the beneficial effects of long-term modafinil therapy. Long-term modafinil therapy may ameliorate the sleep disturbances of Prader-Willi syndrome and should be the focus of future clinical trials.

  13. PET scan perfusion imaging in the Prader-Willi syndrome: new insights into the psychiatric and social disturbances

    International Nuclear Information System (INIS)

    Mantoulan, C.; Payoux, P.; Mantoulan, C.; Diene, G.; Glattard, M.; Molinas, C.; Tauber, M.; Payoux, P.; Sevely, A.; Glattard, M.; Roge, B.; Molinas, C.; Tauber, M.; Zilbovicius, M.; Celsis, P.; Celsis, P.

    2011-01-01

    The Prader-Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H(2)(15)O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypo-perfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship (P≤0.05) between rCBF in the hypo-perfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals. (authors)

  14. Neonatal Features of The Prader-Willi Syndrome; The Case for Making The Diagnosis During The First Week of Life.

    Science.gov (United States)

    Çizmecioğlu, Filiz Mine; Jones, Jeremy Huw; Forsyth Paterson, Wendy; Kherra, Sakina; Kourime, Mariam; McGowan, Ruth; Shaikh, M Guftar; Donaldson, Malcolm

    2018-03-19

    Early diagnosis is of proven benefit in Prader-Willi syndrome (PWS). We therefore examined key perinatal features to aid early recognition. Data were collected from case records of subjects attending a multi-disciplinary clinic and from a retrospective birth questionnaire. Ninety patients (54 male: 36 female) were seen between 1991-2015, most with paternal deletion (n=56) or maternal isodisomy (n=26). Features included cryptorchidism in 94% males, preterm birth (26%), birthweight 28 days: 1-12 months in 7; and 3.75-10.5 years in 5. Typical PWS features in these 12 infants included hypotonia (100%), feeding difficulties (75%), cryptorchidism (83% males) and reduced FM (66%). Causes other than PWS including neuromuscular disease were considered in nine patients. Neonatal hypotonia, reduced FM, feeding difficulties and cryptorchidism should immediately suggest PWS, yet late diagnosis continues in some cases. Awareness of the typical features of PWS in newborn units is required to allow prompt detection even in the presence of confounding factors such as prematurity.

  15. SNORD116 deletions cause Prader-Willi syndrome with a mild phenotype and macrocephaly.

    Science.gov (United States)

    Fontana, P; Grasso, M; Acquaviva, F; Gennaro, E; Galli, M L; Falco, M; Scarano, F; Scarano, G; Lonardo, F

    2017-10-01

    Prader-Willi syndrome is a complex condition caused by lack of expression of imprinted genes in the paternally derived region of chromosome 15 (15q11q13). A small number of patients with Prader-Willi phenotype have been discovered to have narrow deletions, not encompassing the whole critical region, but only the SNORD116 cluster, which includes genes codifying for small nucleolar RNAs. This kind of deletion usually is not detected by the classic DNA methylation analysis test. We present the case of a male patient with a mild Prader-Willi phenotype and a small deletion including SNORD116, diagnosed by methylation-sensitive multiplex ligation-dependent probe amplification (MLPA. The patient showed neonatal hypotonia, hyperphagia, obesity, central hypogonadism, hypothyroidism, strabismus. Stature and intellectual development are within the normal range. The presence of macrocephaly, observed in other cases of SNORD116 deletions as well, is uncommon for the classic phenotype of the syndrome. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Clinical implications of gait analysis in the rehabilitation of adult patients with "Prader-Willi" Syndrome: a cross-sectional comparative study ("Prader-Willi" Syndrome vs matched obese patients and healthy subjects

    Directory of Open Access Journals (Sweden)

    Baccalaro Gabriele

    2007-05-01

    Full Text Available Abstract Background Being severely overweight is a distinctive clinical feature of Prader-Willi Syndrome (PWS. PWS is a complex multisystem disorder, representing the most common form of genetic obesity. The aim of this study was the analysis of the gait pattern of adult subjects with PWS by using three-Dimensional Gait Analysis. The results were compared with those obtained in a group of obese patients and in a group of healthy subjects. Methods Cross-sectional, comparative study: 19 patients with PWS (11 males and 8 females, age: 18–40 years, BMI: 29.3–50.3 kg/m2; 14 obese matched patients (5 males and 9 females, age: 18–40 years, BMI: 34.3–45.2 kg/m2; 20 healthy subjects (10 males and 10 females, age: 21–41 years, BMI: 19.3–25.4 kg/m2. Kinematic and kinetic parameters during walking were assessed by an optoelectronic system and two force platforms. Results PWS adult patients walked slower, had a shorter stride length, a lower cadence and a longer stance phase compared with both matched obese, and healthy subjects. Obese matched patients showed spatio-temporal parameters significantly different from healthy subjects. Furthermore, Range Of Motion (ROM at knee and ankle, and plantaflexor activity of PWS patients were significantly different between obese and healthy subjects. Obese subjects revealed kinematic and kinetic data similar to healthy subjects. Conclusion PWS subjects had a gait pattern significantly different from obese patients. Despite that, both groups had a similar BMI. We suggest that PWS gait abnormalities may be related to abnormalities in the development of motor skills in childhood, due to precocious obesity. A tailored rehabilitation program in early childhood of PWS patients could prevent gait pattern changes.

  17. Mosaic maternal uniparental disomy of chromosome 15 in Prader-Willi syndrome: utility of genome-wide SNP array.

    Science.gov (United States)

    Izumi, Kosuke; Santani, Avni B; Deardorff, Matthew A; Feret, Holly A; Tischler, Tanya; Thiel, Brian D; Mulchandani, Surabhi; Stolle, Catherine A; Spinner, Nancy B; Zackai, Elaine H; Conlin, Laura K

    2013-01-01

    Prader-Willi syndrome is caused by the loss of paternal gene expression on 15q11.2-q13.2, and one of the mechanisms resulting in Prader-Willi syndrome phenotype is maternal uniparental disomy of chromosome 15. Various mechanisms including trisomy rescue, monosomy rescue, and post fertilization errors can lead to uniparental disomy, and its mechanism can be inferred from the pattern of uniparental hetero and isodisomy. Detection of a mosaic cell line provides a unique opportunity to understand the mechanism of uniparental disomy; however, mosaic uniparental disomy is a rare finding in patients with Prader-Willi syndrome. We report on two infants with Prader-Willi syndrome caused by mosaic maternal uniparental disomy 15. Patient 1 has mosaic uniparental isodisomy of the entire chromosome 15, and Patient 2 has mosaic uniparental mixed iso/heterodisomy 15. Genome-wide single-nucleotide polymorphism array was able to demonstrate the presence of chromosomally normal cell line in the Patient 1 and trisomic cell line in Patient 2, and provide the evidence that post-fertilization error and trisomy rescue as a mechanism of uniparental disomy in each case, respectively. Given its ability of detecting small percent mosaicism as well as its capability of identifying the loss of heterozygosity of chromosomal regions, genome-wide single-nucleotide polymorphism array should be utilized as an adjunct to the standard methylation analysis in the evaluation of Prader-Willi syndrome. Copyright © 2012 Wiley Periodicals, Inc.

  18. Gastro-oesophageal reflux - an important causative factor of severe tooth wear in Prader-Willi syndrome?

    Science.gov (United States)

    Saeves, Ronnaug; Strøm, Finn; Sandvik, Leiv; Nordgarden, Hilde

    2018-04-23

    Prader-Willi syndrome (PWS) is the most common genetic human obesity syndrome and is characterized by hypotonia, endocrine disturbances, hyperphagia, obesity and mild mental retardation. Oral abnormalities, such as decreased salivary flow rates and extreme tooth wear, have also been described. Studies have shown a significant increase in reflux symptoms in individuals with obstuctive sleep apnoea syndrome and increased BMI, both of which are typical findings in PWS. Gastro-oesophageal reflux disease (GORD) has been identified in some individuals with PWS and is a significant intrinsic factor in dental tooth wear. The aim of this study was therefore to estimate the prevalence of GORD in adults and children and to evaluate a possible correlation between GORD and tooth wear in adults with PWS. They were all registered at the TAKO-centre. Twenty-nine individuals, 17 adults with a mean age of 32.6 years (range 18-48) and 12 children with a mean age of 8.8 years (range 3-17), agreed to undergo 24-hour oesophageal pH monitoring, and 90% of those enrolled managed to complete the examination. Four children and eleven adults were diagnosed with pathological gastro-oesophageal reflux, which is defined as acid exposure (pH less than 4) more than 3.6 or 4.3 percent of the time, respectively. Manometry performed in the adult group showed a pathologically high lower oesophageal sphincter pressure in four of the five individuals who had normal oesophageal pH values (pH under 4 less than 4.3% of the time). The two groups (reflux and non-reflux) were well balanced according to BMI, genotype, tooth grinding and hyposalivation. However, twice as many individuals in the reflux group as in the non-reflux group reported high consumption of acidic foods and drinks. Increased tooth wear was significantly correlated with GORD in the two groups (reflux n=6 and non-reflux n=6). The prevalence of gastro-oesophageal reflux is high in individuals with PWS. Tooth wear was strongly associated with

  19. Treatment of scoliosis in patients affected with Prader-Willi syndrome using various techniques

    Directory of Open Access Journals (Sweden)

    Cioni Alfredo

    2010-06-01

    Full Text Available Abstract Background The incidence of spinal deformity in children with Prader-Willi syndrome (PWS is high, with 86% of these patients found to have a significant structural scoliosis; however, there are very few case reports describing surgical treatment for this deformity. Methods The authors reviewed a case series consisting of 6 patients who underwent spine surgery for scoliosis. Children's mean age at index surgery was 12 years and 10 months (range, 10 to 15 yrs. Clinical evaluation revealed the typical phenotypic features of the PWS in all of the patients; 4 subjects had a karyotype confirmation of PWS. Major structural curves showed preoperative mean Cobb angles of 80.8° (range, 65° to 96°. Hybrid instrumentation with sublaminar wires, hooks and screws was used in the first 2 patients, while the remaining 4 were treated with titanium pedicle screw constructs. Results The mean clinical and radiological follow-up was 3 years and 10 months (range, 2 years to 9 years. Major complication rate was 50%. One patient who developed a major intraoperative complication (paraparesis prevented spinal fusion to be obtained: the neurologic deficit resolved completely after instrumentation removal. Solid arthrodesis and deformity correction in both coronal and sagittal plane was, however, achieved in the other 5 cases and no significant curve progression was observed at follow-up. Another major short-term complication was encountered 3 months after surgery in a patient who experienced the detachment of a distally located rod and required correction through revision surgery and caudal extension by one level. Cervico-thoracic kyphosis was seen in 1 patient who did not require revision surgery. Conclusions Spine reconstructive surgery in patients with PWS is rare and highly demanding. The best method of reconstruction is posterior multilevel pedicle screw fixation. Moreover, even with modern techniques, the risk of complications is still high. These new

  20. Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy

    Energy Technology Data Exchange (ETDEWEB)

    Cassidy, S.B.; Lai, Li-Wen; Erickson, R.P. (Univ. of Arizona College of Medicine, Tucson, AZ (United States)); Magnuson, L.; Thomas, E.; Herrmann, J. (Great Lakes Genetics, Milwaukee, AZ (United States)); Gendron, R. (Great Lakes Genetics, Kingsport, TN (United States))

    1992-10-01

    Uniparental disomy has recently been recognized to cause human disorders, including Prader-Willi syndrome (PWS). The authors describe a particularly instructive case which raises important issues concerning the mechanisms producing uniparental disomy and whose evaluation provides evidence that trisomy may precede uniparental disomy in a fetus. Chorionic villus sampling performed for advanced maternal age revealed trisomy 15 in all direct and cultured cells, though the fetus appeared normal. Chromosome analysis of amniocytes obtained at 15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and high-resolution banding failed to reveal the deletion of 15q11-13, a deletion which is found in 50%-70% of patients with PWS. Over time, typical features of PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a normal sperm, followed by loss of the paternal 15, is a likely cause of confined placental mosaicism and uniparental disomy in this case of PWS, and advanced maternal age may be a predisposing factor. 38 refs., 3 figs., 2 tabs.

  1. Growth hormone improves body composition and motor development in infants with Prader-Willi syndrome after six months.

    Science.gov (United States)

    Whitman, Barbara; Carrel, Aaron; Bekx, Tracy; Weber, Colleen; Allen, David; Myers, Susan

    2004-04-01

    Infants with Prader-Willi syndrome (PWS) show abnormalities of body composition. Children with PWS treated with growth hormone (GH) demonstrate improved body composition and motor skills. To assess body composition and motor changes in infants with PWS following 6 months GH therapy. Twenty-five infants with PWS (mean age 15.5 mo) underwent dual energy X-ray absorptiometry (DEXA) assessment of body composition, and motor assessment with the Toddler Infant Motor Evaluation (TIME). Patients were then randomized to treatment (Genotropin, 1 mg/m2/day) or control, with reassessment at 6 months. GH treatment significantly increased lean body mass (6.4 +/- 2.4 kg to 8.9 +/- 2.7 kg) and decreased body fat (27.6 +/- 9.9% to 22.4 +/- 10.3%). Age equivalent motor scores improved 4 months in the treated group vs 2 months in controls (p development improvement following 6 months GH therapy. We are investigating whether this improvement leads to long-term reductions in obesity.

  2. Lack of Postprandial Peak in Brain-Derived Neurotrophic Factor in Adults with Prader-Willi Syndrome.

    Directory of Open Access Journals (Sweden)

    Marta Bueno

    Full Text Available Prader-Willi syndrome (PWS is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF and leptin are reciprocally involved in energy homeostasis.To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS.Experimental study.University hospital.90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls.Subjects ingested a liquid meal after fasting ≥10 hours.Leptin and BDNF levels in plasma extracted before ingestion and 30', 60', and 120' after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60' and 120' after ingestion.Fasting BDNF levels were lower in PWS than in controls (p = 0.05. Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p<0.05. Leptin was higher in PWS patients than in controls at all time points (p<0.001. PWS patients were hungrier than controls before and after eating. The probability of being hungry was associated with baseline BDNF levels: every 50-unit increment in BDNF decreased the odds of being hungry by 22% (OR: 0.78, 95%CI: 0.65-0.94. In uniparental disomy, the odds of being hungry decreased by 66% (OR: 0.34, 90%CI: 0.13-0.9. Postprandial leptin patterns did no differ among genetic subtypes.Low baseline BDNF levels and lack of postprandial peak may contribute to persistent hunger after meals. Uniparental disomy is the genetic subtype of PWS least affected by these factors.

  3. Two years of growth hormone therapy in young children with Prader-Willi syndrome: physical and neurodevelopmental benefits.

    Science.gov (United States)

    Myers, Susan E; Whitman, Barbara Y; Carrel, Aaron L; Moerchen, Victoria; Bekx, M Tracy; Allen, David B

    2007-03-01

    Infants with Prader-Willi syndrome (PWS) typically display failure to thrive and decreased muscle mass with excess body fat for age. Growth hormone (GH) therapy in children with PWS improves, but does not normalize, body composition and muscle strength and agility. The objective of this study was to determine the effects of earlier GH therapy on anthropometric measurements, body composition, and psychomotor development in affected PWS infants and toddlers. Twenty-five subjects, ages 4-37 months, were randomized to 2 years of GH therapy (1 mg/m(2)/day) or 1 year of observation without GH treatment and then placed on GH (1.5 mg/m(2).day) for 1 year only. Anthropometric measurements were obtained by standard methods: percent body fat, lean body mass, and total body bone mineral density by dual x-ray absorptiometry; motor constructs of mobility and stability by the Toddler Infant Motor Evaluation; and cognitive and language function by the Capute Scales of Infant Language and Cognitive Development. GH-treated PWS subjects demonstrated normalization of length/height standard deviation scores (SDS), faster head growth, increased lean body mass accrual, and decreased percent body fat (P < 0.005 for all parameters), as well as improved language (P = 0.05) and cognitive (P = 0.02) quotient Z-scores compared with similarly aged untreated PWS subjects after 1 year into the study. PWS subjects treated before their first birthday spoke their first words at a mean age of 14.4 +/- 2.8 months and walked independently at 23.3 +/- 4.8 months. GH therapy was well-tolerated; however, one PWS subject experienced scoliosis progression. As greater benefits were seen in our study with early treatment, prompt referral to a pediatric endocrinologist for consideration of GH therapy is recommended for PWS at an early age. (c) 2006 Wiley-Liss, Inc.

  4. Childhood subdural hemorrhage, macrocephaly, and coagulopathy associated with Prader-Willi syndrome: case report and review of the literature.

    Science.gov (United States)

    Carr, Robert B; Khanna, Paritosh C; Saneto, Russell P

    2012-07-01

    A 16-month-old girl with a history of Prader-Willi syndrome and progressive macrocephaly manifested large, bilateral, subdural hemorrhages of differing ages on magnetic resonance imaging. Subsequent evaluation revealed a deficiency of von Willebrand factor, but after repeated evaluations, no conclusive evidence of nonaccidental trauma became apparent. Subdural hemorrhages of varying ages are frequently associated with nonaccidental trauma during early childhood. However, several uncommon conditions may present as subdural hemorrhages and thus mimic nonaccidental trauma. Our patient demonstrates a combination of Prader-Willi syndrome, von Willebrand factor deficiency, and enlargement of the extra-axial spaces. All of these in isolation were associated with subdural hemorrhages. We review the scant literature on subdural hemorrhages in Prader-Willi syndrome and other conditions that mimic nonaccidental trauma. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. 6q16.3q23.3 duplication associated with Prader-Willi-like syndrome.

    Science.gov (United States)

    Desch, Laurent; Marle, Nathalie; Mosca-Boidron, Anne-Laure; Faivre, Laurence; Eliade, Marie; Payet, Muriel; Ragon, Clemence; Thevenon, Julien; Aral, Bernard; Ragot, Sylviane; Ardalan, Azarnouche; Dhouibi, Nabila; Bensignor, Candace; Thauvin-Robinet, Christel; El Chehadeh, Salima; Callier, Patrick

    2015-01-01

    Prader-Willi syndrome (PWS) is characterized by hypotonia, delayed neuropsychomotor development, overeating, obesity and mental deficiency. This phenotype is encountered in other conditions, defining Prader-Willi-like syndrome (PWLS). We report a 14-year-old boy with a complex small supernumerary marker chromosome (sSMC) associated with PWLS. The propositus presents clinical features commonly found in patients with PWLS, including growth hormone deficit. Banding karyotype analysis and fluorescence in situ hybridization (FISH) revealed a marker derived from chromosome 6 and a neocentromere as suspected, but array-CGH enabled us to characterize this marker as a der(10)t(6;10)(6qter → 6q23.3::10p11.1 → 10p11.21)dn. As far as we know, this is the first diagnosed case of PWLS associated with a complex sSMC, involving a 30.9 Mb gain in the 6q16.3q23.3 region and a 3.5 Mb gain in the 10p11.21p11.1 region. Several genes have been mapped to the 6q region including the TCBA1 gene, which is associated with developmental delay and recurrent infections, the ENPP1 gene, associated with insulin resistance and susceptibility to obesity and the BMIQ3 gene, associated with body mass index (BMI). No OMIM gene was found in the smallest 10p11.21p11.1 region. We suggest that the duplicated chromosome segment 6q16.3q23.3 may be responsible for the phenotype of our case and may also be a candidate locus of PWLS.

  6. Tenth annual scientific conference of the Prader-Willi Syndrome Association (USA), July 19, 1995, Seattle, Washington

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    Holm, V.A.; Hudgins, L. [Univ. of Washington School of Medicine, Seattle, WA (United States); Cassidy, S.B. [Univ. of Washington School of Medicine, and Children`s Hospital and Medical Center, Seattle, WA (United States)]|[Univ. Hospitals of Cleveland, OH (United States)

    1996-09-06

    Each year for the last 10 years, scientists conducting research on Prader-Willi syndrome have come together to exchange information during a scientific conference held in conjunction with the annual Prader-Willi Syndrome Association (USA) meeting. Presentations based on submitted abstracts encompass such varied fields as genetics, endocrinology, pediatrics, nutrition, psychology, psychiatry, and education. This year`s scientific conference was held in Seattle, Washington, on July 19, 1995, in conjunction with the 14th PWSA (USA) meeting held July 20-23. Seventeen reports were presented at the scientific meeting, the abstracts of which follow.

  7. Endocrine problems in children with Prader-Willi syndrome: special review on associated genetic aspects and early growth hormone treatment

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Jin

    2012-07-01

    Full Text Available Prader-Willi syndrome (PWS is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features include neonatal hypotonia, distinctive facial features, overall developmental delay, and poor growth in infancy, followed by overeating with severe obesity, short stature, and hypogonadism later in development. This paper reviews recent updates regarding the genetic aspects of this disorder. Three mechanisms (paternal deletion, maternal disomy, and deficient imprinting are recognized. Maternal disomy can arise because of 4 possible mechanisms: trisomy rescue (TR, gamete complementation (GC, monosomy rescue (MR, and postfertilization mitotic nondisjunction (Mit. Recently, TR/GC caused by nondisjunction at maternal meiosis 1 has been identified increasingly, as a result of advanced maternal childbearing age in Korea. We verified that the d3 allele increases the responsiveness of the growth hormone (GH receptor to endogenous GH. This paper also provides an overview of endocrine dysfunctions in children with PWS, including GH deficiency, obesity, sexual development, hypothyroidism, and adrenal insufficiency, as well as the effects of GH treatment. GH treatment coupled with a strictly controlled diet during early childhood may help to reduce obesity, improve neurodevelopment, and increase muscle mass. A more active approach to correct these hormone deficiencies would benefit patients with PWS.

  8. The Prader-Willi syndrome proteins MAGEL2 and necdin regulate leptin receptor cell surface abundance through ubiquitination pathways.

    Science.gov (United States)

    Wijesuriya, Tishani Methsala; De Ceuninck, Leentje; Masschaele, Delphine; Sanderson, Matthea R; Carias, Karin Vanessa; Tavernier, Jan; Wevrick, Rachel

    2017-11-01

    In Prader-Willi syndrome (PWS), obesity is caused by the disruption of appetite-controlling pathways in the brain. Two PWS candidate genes encode MAGEL2 and necdin, related melanoma antigen proteins that assemble into ubiquitination complexes. Mice lacking Magel2 are obese and lack leptin sensitivity in hypothalamic pro-opiomelanocortin neurons, suggesting dysregulation of leptin receptor (LepR) activity. Hypothalamus from Magel2-null mice had less LepR and altered levels of ubiquitin pathway proteins that regulate LepR processing (Rnf41, Usp8, and Stam1). MAGEL2 increased the cell surface abundance of LepR and decreased their degradation. LepR interacts with necdin, which interacts with MAGEL2, which complexes with RNF41 and USP8. Mutations in the MAGE homology domain of MAGEL2 suppress RNF41 stabilization and prevent the MAGEL2-mediated increase of cell surface LepR. Thus, MAGEL2 and necdin together control LepR sorting and degradation through a dynamic ubiquitin-dependent pathway. Loss of MAGEL2 and necdin may uncouple LepR from ubiquitination pathways, providing a cellular mechanism for obesity in PWS. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Effects of exenatide on weight and appetite in overweight adolescents and young adults with Prader-Willi syndrome.

    Science.gov (United States)

    Salehi, P; Hsu, I; Azen, C G; Mittelman, S D; Geffner, M E; Jeandron, D

    2017-06-01

    Prader-Willi syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity because of obesity without effective medical treatment targeting hyperphagia. Exenatide (Byetta [synthetic Exendin-4]; AstraZeneca, Wilmington DE) is a GLP-1 receptor agonist which reduces appetite and weight and may be an effective treatment in PWS. The objective of this study is to determine the effect of a 6-month trial of exenatide on appetite, weight and gut hormones in youth with PWS. Ten overweight and obese subjects with PWS (13-25 years) were recruited for a 6-month open-label, non-randomized, longitudinal study conducted at Children's Hospital Los Angeles. Exenatide was given using standard diabetes dosing without dietary modifications. Weight, body mass index (BMI), truncal fat, appetite and plasma acylated ghrelin were measured over 6 months. Mixed meal tolerance tests were performed at 0 and 6 months. Appetite scores significantly decreased from baseline (32.2 ± 8.7) after 1, 3 and 6 moths of treatment (27.5 ± 8.8, 25.4 ± 9.3, and 25.4 ± 7.2 respectively; p = 0.004). Hemoglobin A1c decreased significantly after treatment, but weight, BMI z-score and adiposity did not. There was no significant change in ghrelin. This is the first longitudinal investigation of the effects of exenatide in subjects with PWS. It was effective in decreasing appetite, without change in weight or BMI in the short term. Larger, controlled, longer-term trials in patients with PWS are needed to confirm the efficacy and safety of exenatide and to evaluate whether its use might induce weight loss when given in conjunction with behavioural modification. © 2016 World Obesity Federation.

  10. A twin sibling with Prader-Willi syndrome caused by uniparental disomy conceived after in vitro fertilization.

    Science.gov (United States)

    Atik, T; Aykut, A; Karaca, E; Onay, H; Ozkinay, F; Cogulu, O

    2014-01-01

    The use of assisted reproductive technologies (ART) has increased gradually in the treatment of infertility worldwide. On the other hand ART has been found to be associated with an increased risk of congenital malformations including imprinting defects as well. Although a number of imprinting syndromes have been reported to be related with ART, no case with uniparental disomy (UPD) caused Prader-Willi syndrome (PWS) [OMIM ID: 176270] has been reported in the literature. Here we present a dizygotic twin in which one of them was born with maternal UPD15 following ART. The proband was a 2-year-old boy who had feeding difficulties, generalized hypotonia, frontal bossing, broad forehead, small hands and feet. Laboratory investigations revealed minimal dilatation in 3rd and 4th ventricles and corpus callosum hypoplasia in magnetic resonance imaging, supravalvular pulmonary stenosis in echocardiography and pelvicaliectasia in the USG examinations. Methylation and microsatellite markers analyses showed maternal UPD for chromosome 15. Here we report, for the first time UPD caused PWS patient born after ART.

  11. [Prader-Willi syndrome case with proliferative diabetic retinopathy in both eyes treated by early vitrectomy under local anesthesia].

    Science.gov (United States)

    Hori, Hideyuki; Sato, Yukihiro; Nakashima, Motohiro; Nakajima, Motohiro

    2012-02-01

    Although patients with Prader-Willi syndrome have a high rate of diabetes, to date, there have been only 4 reported cases (6 eyes) undergoing vitrectomy for proliferative diabetic retinopathy. Herein, we report a case of Prader-Willi syndrome with proliferative diabetic retinopathy that was treated by early vitrectomy OU under local anesthesia. A 30-year-old man was diagnosed as having Prader-Willi syndrome at the age of 2 years and diabetes at age 17. He was referred to our hospital as diabetic retinopathy had been detected in his first ophthalmological examination at age 29. Visual acuity was 0.6 bilaterally. Proliferative retinopathy, with cataract and macular edema, was identified in both eyes. Panretinal photocoagulation was performed on both eyes. However, proliferative membranes developed bilaterally, and vitreous hemorrhage occurred OS. Visual acuity decreased to 0.3 OU. The patient was hospitalized at our internal medicine department for blood glucose control. Subsequently, with an anesthesiologist on standby, a hypnotic sedative was injected intramuscularly, achieving retro-bulbar anesthesia. Combined cataract and vitreous surgery was performed on the left eye. One week later, a similar operation was performed on the right eye. The patient was discharged four days later. In the two years since these operation, visual acuity has been maintained at 0.8 OU. Patients with Prader-Willi syndrome should be examined for early detection and treatment of diabetic retinopathy.

  12. Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome.

    Science.gov (United States)

    Festen, D A M; Wevers, M; Lindgren, A C; Böhm, B; Otten, B J; Wit, J M; Duivenvoorden, H J; Hokken-Koelega, A C S

    2008-06-01

    Prader-Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, feeding difficulties and failure to thrive in infancy. GH treatment improves growth velocity and body composition. Research on the effects of GH on psychomotor development in infants with PWS is limited. To evaluate psychomotor development in PWS infants and toddlers during GH treatment compared to randomized controls. Forty-three PWS infants were evaluated at baseline. Twenty-nine of them were randomized into a GH group (n = 15) receiving 1 mg/m(2)/day GH or a non-GH-treated control group (n = 14). At baseline and after 12 months of follow-up, analysis with Bayley Scales of Infant Development II (BSID-II) was performed. Data were converted to percentage of expected development for age (%ed), and changes during follow-up were calculated. Infants in the GH group had a median age of 2.3 years [interquartile range (IQR) 1.7-3.0] and in the control group of 1.5 years (IQR 1.2-2.7) (P = 0.17). Both mental and motor development improved significantly during the first year of study in the GH group vs. the control group: median (IQR) change was +9.3% (-5.3 to 13.3) vs.-2.9% (-8.1 to 4.9) (P development and +11.2% (-4.9 to 22.5) vs.-18.5% (-27.9 to 1.8) (P development, respectively. One year of GH treatment significantly improved mental and motor development in PWS infants compared to randomized controls.

  13. Impaired theory of mind and symptoms of Autism Spectrum Disorder in children with Prader-Willi syndrome.

    Science.gov (United States)

    Lo, Sin Ting; Siemensma, Elbrich; Collin, Philippe; Hokken-Koelega, Anita

    2013-09-01

    In order to evaluate the social cognitive functioning in children with Prader-Willi syndrome (PWS), Theory of Mind (ToM) and symptoms of Autism Spectrum Disorder were evaluated. Sixty-six children with PWS aged 7-17 years were tested using the Theory of Mind test-R and the Diagnostic Interview for Social Communication disorders. We tested the correlation between Total ToM Standard Deviation Score (Total ToM SDS) and genetic subtype of paternal deletion or maternal uniparental disomy, and total IQ, verbal IQ and performal IQ. Prevalence and symptoms of Autism Spectrum Disorder were assessed. Median (interquartile range) of total ToM SDS of those aged 7-17 years was -3.84 (-5.73, -1.57). Their Total ToM SDS correlated with total IQ (β=0.662, p0.05, adj.R(2)=0.259). No difference in Total ToM SDS was found between children with deletion and maternal uniparental disomy (β=-0.143, p>0.05, adj.R(2)=-0.016). Compared to the reference group of healthy children aged 7-12 years, children with PWS in the same age group had a median ToM developmental delay of 4 (3-5) years. One third of children with PWS scored positive for Autism Spectrum Disorder. Most prominent aberrations in Autism Spectrum Disorder were focused on maladaptive behavior. Our findings demonstrate a markedly reduced level of social cognitive functioning, which has consequences for the approach of children with PWS, i.e. adjustment to the child's level of social cognitive functioning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. A reduced-energy intake, well-balanced diet improves weight control in children with Prader-Willi syndrome.

    Science.gov (United States)

    Miller, J L; Lynn, C H; Shuster, J; Driscoll, D J

    2013-02-01

    Children with Prader-Willi syndrome (PWS) have a predictable pattern of weight gain, with obesity beginning in early childhood and worsening as they get older and hyperphagia increases. Data on the most effective dietary modifications are scant and primarily anecdotal. As part of a longitudinal study investigating the natural history of PWS, we evaluated the effect of a well-balanced, energy-restricted diet on body composition and weight in young children with PWS. Sixty-three children, aged 2-10 years, with genetically proven PWS participated in the present study. These children had measurements of body composition by dual-energy X-ray absorptiometry and resting energy expenditure (REE), as well as a 3-day diet history analysis both before and after intervention. Energy calculations were based on the individual's REE, with the recommendation that the macronutrients of the diet consist of 30% fat, 45% carbohydrates and 25% protein, with at least 20 g of fibre per day. Thirty-three families adhered to our dietary recommendations for both energy intake and macronutrient distribution. Those 33 children had lower body fat (19.8% versus 41.9%; P diet. Those who followed our recommendations also had a lower respiratory quotient (0.84 versus 0.95; P = 0.002). Our recommendation for an energy-restricted diet with a well-balanced macronutrient composition and fibre intake improves both weight and body composition in children with PWS compared to a simple energy-restricted diet. © 2012 The Authors. Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.

  15. A reduced-energy intake, well-balanced diet improves weight control in children with Prader-Willi syndrome

    Science.gov (United States)

    Miller, J. L.; Lynn, C. H.; Shuster, J.; Driscoll, D. J.

    2014-01-01

    Background Children with Prader-Willi syndrome (PWS) have a predictable pattern of weight gain, with obesity beginning in early childhood and worsening as they get older and hyperphagia increases. Data on the most effective dietary modifications are scant and primarily anecdotal. As part of a longitudinal study investigating the natural history of PWS, we evaluated the effect of a well-balanced, energy-restricted diet on body composition and weight in young children with PWS. Methods Sixty-three children, aged 2–10 years, with genetically proven PWS participated in the present study. These children had measurements of body composition by dual-energy X-ray absorptiometry and resting energy expenditure (REE), as well as a 3-day diet history analysis both before and after intervention. Energy calculations were based on the individual's REE, with the recommendation that the macronutrients of the diet consist of 30% fat, 45% carbohydrates and 25% protein, with at least 20 g of fibre per day. Results Thirty-three families adhered to our dietary recommendations for both energy intake and macronutrient distribution. Those 33 children had lower body fat (19.8% versus 41.9%; P diet. Those who followed our recommendations also had a lower respiratory quotient (0.84 versus 0.95; P = 0.002). Conclusions Our recommendation for an energy-restricted diet with a well-balanced macronutrient composition and fibre intake improves both weight and body composition in children with PWS compared to a simple energy-restricted diet. PMID:23078343

  16. Prader-Willi syndrome and atypical submicroscopic 15q11-q13 deletions with or without imprinting defects.

    Science.gov (United States)

    Hassan, Maaz; Butler, Merlin G

    2016-11-01

    We report a 20 year follow up on a Caucasian female, now 26 years of age, with Prader-Willi syndrome (PWS) harboring an atypical 15q11-q13 submicroscopic deletion of 100-200 kb in size first detected in 1996 involving the imprinting center, SNRPN gene and surrounding region. PWS is a rare complex disorder caused by the loss of paternally expressed genes in the 15q11-q13 region. With high resolution chromosomal microarray and methylation - specific MLPA analysis, we updated the genetic findings on our patient and found a 209,819bp deletion including the SNURF-SNRPN gene complex which includes the imprinting center and the SNORD116 region. We compared with four other similarly reported individuals in the literature with atypical submicroscopic deletions within this region but without imprinting center involvement to better characterize the specific genetic lesions causing PWS clinical findings. Clinically, our patient met the diagnostic criteria of PWS including infantile hypotonia, a poor suck with feeding difficulties, global developmental delays and later food foraging, childhood obesity, small hands and skin picking. Small atypical deletions of comparable sizes were seen in the 15q11-q13 region in all five cases and similar behavioral/physical characteristics were found despite an imprinting defect in our patient. These results further support an overlapping critical deletion region involving the non-coding snoRNA SNORD116 in common in the five individuals playing a key role in contributing to the PWS phenotype. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. A twin sibling with Prader-Willi syndrome caused by type 2 microdeletion following assisted reproductive technology: A case report.

    Science.gov (United States)

    Han, Ji Yoon; Park, Joonhong; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo

    2016-07-01

    Prader-Willi syndrome (PWS) is a neurobehavioral imprinting disorder, which arises due to an absence of paternally expressed genes within the 15q11.2-q13 region. This occurs via one of the three main genetic mechanisms, as follows: Deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. Recent studies have reported an association between imprinting disorders and assisted reproductive technologies (ART). The current study presents a 6-year-old female patient who is a dizygotic twin, in which one was born with de novo microdeletion at 15q11.2-q13.1 following in vitro fertilization. The patient had characteristic facial features including narrow bifrontal diameter, strabismus, downturned mouth, feeding problems and generalized hypotonia during infancy, developmental delay, mental retardation and rapid weight gain. Based upon phenotypic resemblance and the medical records, methylation-specific multiplex ligation-dependent probe amplification and array-based comparative genome hybridization analyses demonstrate type 2 microdeletion between breaking point 2 (BP2) and BP3, which occur from MKRN3 through HERC2 at 15q11.2-q13.1. To the best of our knowledge, the present study is the first to report a PWS case born following ART reported in South Korea. In addition to previous studies, the present study contributes to the consensus regarding genotype-phenotype comparisons in this respect.

  18. [Endocrine and metabolic features of female children with Prader-Willi syndrome: an analysis of 4 cases].

    Science.gov (United States)

    Wu, Mo-Ling; Li, Juan; Ding, Yu; Chen, Yao; Chang, Guo-Ying; Wang, Xiu-Min; Wang, Jian; Shen, Yi-Ping

    2017-05-01

    This article reports the clinical features and endocrine and metabolic features of 4 children with Prader-Willi syndrome (PWS). All the patients were female and aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity, unusual facies, developmental retardation, and intellectual disability. Genetic detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region, one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of endocrine and metabolic disorders: 2 patients had short stature, among whom one had delayed appearance of secondary sex characteristics and the other one had type 2 diabetes; one patient had insulin resistance and no mammary gland development; one patient had a body height of P 3 -P 10 and precocious puberty. Patients with PWS have various endocrine disorders, so long-term endocrine follow-up and management is very important.

  19. What Are the Symptoms of Prader-Willi Syndrome?

    Science.gov (United States)

    ... works normally, it controls hunger or thirst, body temperature, pain, and when it is time to awaken ... with PWS have varying levels of intellectual disabilities. Learning disabilities are common, as are delays in starting ...

  20. Prader-Willi-like phenotypes: a systematic review of their chromosomal abnormalities.

    Science.gov (United States)

    Rocha, C F; Paiva, C L A

    2014-03-31

    Prader-Willi syndrome (PWS) is caused by the lack of expression of genes located on paternal chromosome 15q11-q13. This lack of gene expression may be due to a deletion in this chromosomal segment, to maternal uniparental disomy of chromosome 15, or to a defect in the imprinting center on 15q11-q13. PWS is characterized by hypotonia during the neonatal stage and in childhood, accompanied by a delay in neuropsychomotor development. Overeating, obesity, and mental deficiency arise later on. The syndrome has a clinical overlap with other diseases, which makes it difficult to accurately diagnose. The purpose of this article is to review the Prader-Willi-like phenotype in the scientific literature from 2000 to 2013, i.e., to review the cases of PWS caused by chromosomal abnormalities different from those found on chromosome 15. A search was carried out using the "National Center for Biotechnology Information" (www.pubmed.com) and "Scientific Electronic Library Online (www.scielo.br) databases and combinations of key words such as "Prader-Willi-like phenotype" and "Prader-Willi syndrome phenotype". Editorials, letters, reviews, and guidelines were excluded. Articles chosen contained descriptions of patients diagnosed with the PWS phenotype but who were negative for alterations on 15q11-q13. Our search found 643 articles about PWS, but only 14 of these matched with the Prader-Willi-like phenotype and with the selected years of publication (2000-2013). If two or more articles reported the same chromosomal alterations for Prader-Willi-like phenotype, the most recent was chosen. Twelve articles of 14 were case reports and 2 reported series of cases.

  1. Healthcare transition in persons with intellectual disabilities: general issues, the Maastricht model, and Prader-Willi syndrome.

    Science.gov (United States)

    Schrander-Stumpel, Constance T R M; Sinnema, Margje; van den Hout, Lieke; Maaskant, Marian A; van Schrojenstein Lantman-de Valk, Henny M J; Wagemans, Annemieke; Schrander, Jaap J P; Curfs, Leopold M G

    2007-08-15

    In current healthcare, transitional healthcare is a very important and timely issue. Thanks to the major advances made in medical care and technology, many children with childhood onset diseases and/or genetic syndromes survive to adulthood. These children are at risk of not being provided with adequate healthcare as they reach adulthood. Healthcare transition is an essential part of healthcare provision, referred to as the shift from one type of healthcare to another. In Maastricht, we developed a transition/out clinic led by a medical doctor specialized in persons with intellectual disability (ID), together with a clinical geneticist. We aim to coordinate healthcare issues based on guidelines if available. Also questions concerning living, daily activities, relations, sexuality, and sterilization can be discussed. The aging process of persons with ID has been a topic of interest in recent years. Little is known about the aging process of people with specific syndromes, except for persons with Down syndrome. We present some data of a recent questionnaire study in persons with Prader-Willi syndrome. In only 50% in persons with a clinical diagnosis genetic test results could be reported. The majority of persons were obese. Diabetes mellitus, hypertension, skin problems, sleep apnea, and hormonal problems like osteoporosis and hypothyroidism were common. Psychiatric problems were frequent, especially in the persons with uniparental disomy. Osteoporosis and sleep apnoea seem to be underestimated. Further longitudinal research is necessary for a better understanding of the aging process in PWS. (c) 2007 Wiley-Liss, Inc.

  2. A case of an atypically large proximal 15q deletion as cause for Prader-Willi syndrome arising from a de novo unbalanced translocation.

    Science.gov (United States)

    Hickey, Scott E; Thrush, Devon Lamb; Walters-Sen, Lauren; Reshmi, Shalini C; Astbury, Caroline; Gastier-Foster, Julie M; Atkin, Joan

    2013-09-01

    We describe an 11 month old female with Prader-Willi syndrome (PWS) resulting from an atypically large deletion of proximal 15q due to a de novo 3;15 unbalanced translocation. The 10.6 Mb deletion extends from the chromosome 15 short arm and is not situated in a region previously reported as a common distal breakpoint for unbalanced translocations. There was no deletion of the reciprocal chromosome 3q subtelomeric region detected by either chromosomal microarray or FISH. The patient has hypotonia, failure to thrive, and typical dysmorphic facial features for PWS. The patient also has profound global developmental delay consistent with an expanded, more severe, phenotype. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome.

    Science.gov (United States)

    Deal, Cheri L; Tony, Michèle; Höybye, Charlotte; Allen, David B; Tauber, Maïthé; Christiansen, Jens Sandahl

    2013-06-01

    Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events. The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS. We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries. Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN). Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks.

  4. QOL in caregivers of Japanese patients with Prader-Willi syndrome with reference to age and genotype.

    Science.gov (United States)

    Ihara, Hiroshi; Ogata, Hiroyuki; Sayama, Masayuki; Kato, Aya; Gito, Masao; Murakami, Nobuyuki; Kido, Yasuhiro; Nagai, Toshiro

    2014-09-01

    This study aimed to measure quality of life (QOL) of the primary family caregivers for patients with Prader-Willi syndrome (PWS). Comparisons were made between caregivers' QOL in regard to their dependents' genotype and age group. The participants with PWS consisted of 22 children (aged from 6 to 12 years) and 23 adolescents (aged from 13 to 19 years), including 6 children and 7 adolescents with maternal uniparental disomy (mUPD) and 16 children and 16 adolescents with deletion (DEL). The QOL of the primary family caregiver for each patient was assessed using the Japanese version of the WHOQOL-BREF. To examine the effect that age (children vs. adolescents) and genotype (DEL vs. mUPD) have on the QOL of caregivers, a two-way ANOVA was conducted, followed by the Bonferroni procedure to test the simple main effects. The two age groups and the two genotypes of PWS were used as independent variables and the total QOL of caregivers as a dependent variable. The two-way ANOVA (F(1, 41) = 6.98, P caregivers of DEL adolescents showed little difference from that with DEL children, but the QOL of caregivers for mUPD adolescents was shown to be lower than that with mUPD children along with that of caregivers with DEL adolescents. There is hence a growing tendency for the deterioration in the QOL of caregivers to manifest itself later in the patients' adolescence, found mainly with mUPD patients. © 2014 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

  5. Physiological adaptation after a 12-week physical activity program for patients with Prader-Willi syndrome: two case reports.

    Science.gov (United States)

    Amaro, Alexandre Slowetzky; Teixeira, Maria Cristina Triguero Veloz; de Mesquita, Maria Luiza Guedes; Rodrigues, Graciele Massoli; Rubin, Daniela Andrea; Carreiro, Luiz Renato Rodrigues

    2016-06-23

    Physical activity programs are a powerful tool against several diseases including obesity and their comorbidities. Prader-Willi syndrome is the most common genetic disease associated with obesity, and brings with it behavioral and emotional problems that need complex management. Research into the effect of physical activity programs on Prader-Willi syndrome is limited and it is frequently argued that if a physical activity program is too complex, the participants are more likely to drop out. Therefore, in this study, we assessed the physiological adaptation effect of a physical activity program with increasing complexity and load, in a boy and a girl with Prader-Willi syndrome by assessing changes in lipid profile, body composition, and physical fitness parameters. Case 1 was an 11-year-old girl, mixed race (brown), with an intelligence quotient of 68, 52.0 % body fat, and a body mass index of 45.3 kg/m(2). The Prader-Willi syndrome diagnosis was made when she was 5-years old and was found to be due to an imprinting genomic defect. Case 2 was a 14-year-old boy, mixed race (brown), with an intelligence quotient of 74, 48.8 % body fat, and a body mass index of 37.3 kg/m(2). The diagnosis was made when he was 10-years old and was found to be caused by gene deletion. Both participants presented physical characteristics and behavior problems typical of Prader-Willi syndrome. Case 2 presented high blood pressure, high cholesterol and sleep apnea and had to use continuous positive airway pressure to sleep. Both participants were assessed for 12 weeks (three times a week) using a physical activity program designed to improve strength and muscle hypertrophy. The work load was progressively adjusted as necessary and new exercises were added to the program. Prior to the program, the participants' parents received instructions about managing problem behavior and advice about nutrition. After physical activity program several health markers assessed by biological tests and

  6. Deletion of the Snord116/SNORD116 Alters Sleep in Mice and Patients with Prader-Willi Syndrome.

    Science.gov (United States)

    Lassi, Glenda; Priano, Lorenzo; Maggi, Silvia; Garcia-Garcia, Celina; Balzani, Edoardo; El-Assawy, Nadia; Pagani, Marco; Tinarelli, Federico; Giardino, Daniela; Mauro, Alessandro; Peters, Jo; Gozzi, Alessandro; Grugni, Graziano; Tucci, Valter

    2016-03-01

    Sleep-wake disturbances are often reported in Prader-Willi syndrome (PWS), a rare neurodevelopmental syndrome that is associated with paternally-expressed genomic imprinting defects within the human chromosome region 15q11-13. One of the candidate genes, prevalently expressed in the brain, is the small nucleolar ribonucleic acid-116 (SNORD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that SNORD116 is responsible for sleep defects that characterize the syndrome. We studied sleep in mutant mice that carry a deletion of Snord116 at the orthologous locus (mouse chromosome 7) of the human PWS critical region (PWScr). In particular, we assessed EEG and temperature profiles, across 24-h, in PWScr (m+/p-) heterozygous mutants compared to wild-type littermates. High-resolution magnetic resonance imaging (MRI) was performed to explore morphoanatomical differences according to the genotype. Moreover, we complemented the mouse work by presenting two patients with a diagnosis of PWS and characterized by atypical small deletions of SNORD116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects. By studying the mouse mutant line PWScr(m+/p-), we observed specific rapid eye movement (REM) sleep alterations including abnormal electroencephalograph (EEG) theta waves. Remarkably, we observed identical sleep/EEG defects in the two PWS cases. We report brain morphological abnormalities that are associated with the EEG alterations. In particular, mouse mutants have a bilateral reduction of the gray matter volume in the ventral hippocampus and in the septum areas, which are pivotal structures for maintaining theta rhythms throughout the brain. In PWScr(m+/p-) mice we also observed increased body temperature that is coherent with REM sleep alterations in mice and human patients. Our study indicates that paternally expressed Snord116 is involved in the 24-h regulation of

  7. Grey matter volume and cortical structure in Prader-Willi syndrome compared to typically developing young adults

    Directory of Open Access Journals (Sweden)

    Katherine E. Manning

    2018-01-01

    Full Text Available Prader-Willi syndrome (PWS is a neurodevelopmental disorder of genomic imprinting, presenting with a characteristic overeating disorder, mild to moderate intellectual disability, and a variable range of social and behavioral difficulties. Consequently, widespread alterations in neural structure and developmental and maturational trajectory would be expected. To date, there have been few quantitative and systematic studies of brain morphology in PWS, although alterations of volume and of cortical organisation have been reported. This study aimed to investigate, in detail, the structure of grey matter and cortex in the brain in a sample of young adults with PWS in a well-matched case-controlled analysis. 20 young adults with PWS, aged 19–27 years, underwent multiparameter mapping magnetic resonance imaging sequences, from which measures of grey matter volume, cortical thickness and magnetisation transfer saturation, as a proxy measure of myelination, were examined. These variables were investigated in comparison to a control group of 40 typically developing young adults, matched for age and sex. A voxel-based morphometry analysis identified large and widespread bilateral clusters of both increased and decreased grey matter volume in the brain in PWS. In particular, widespread areas of increased volume encompassed parts of the prefrontal cortex, especially medially, the majority of the cingulate cortices, from anterior to posterior aspects, insula cortices, and areas of the parietal and temporal cortices. Increased volume was also reported in the caudate, putamen and thalamus. The most ventromedial prefrontal areas, in contrast, showed reduced volume, as did the parts of the medial temporal lobe, bilateral temporal poles, and a small cluster in the right lateral prefrontal cortex. Analysis of cortical structure revealed that areas of increased volume in the PWS group were largely driven by greater cortical thickness. Conversely, analysis of

  8. Grey matter volume and cortical structure in Prader-Willi syndrome compared to typically developing young adults.

    Science.gov (United States)

    Manning, Katherine E; Tait, Roger; Suckling, John; Holland, Anthony J

    2018-01-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a characteristic overeating disorder, mild to moderate intellectual disability, and a variable range of social and behavioral difficulties. Consequently, widespread alterations in neural structure and developmental and maturational trajectory would be expected. To date, there have been few quantitative and systematic studies of brain morphology in PWS, although alterations of volume and of cortical organisation have been reported. This study aimed to investigate, in detail, the structure of grey matter and cortex in the brain in a sample of young adults with PWS in a well-matched case-controlled analysis. 20 young adults with PWS, aged 19-27 years, underwent multiparameter mapping magnetic resonance imaging sequences, from which measures of grey matter volume, cortical thickness and magnetisation transfer saturation, as a proxy measure of myelination, were examined. These variables were investigated in comparison to a control group of 40 typically developing young adults, matched for age and sex. A voxel-based morphometry analysis identified large and widespread bilateral clusters of both increased and decreased grey matter volume in the brain in PWS. In particular, widespread areas of increased volume encompassed parts of the prefrontal cortex, especially medially, the majority of the cingulate cortices, from anterior to posterior aspects, insula cortices, and areas of the parietal and temporal cortices. Increased volume was also reported in the caudate, putamen and thalamus. The most ventromedial prefrontal areas, in contrast, showed reduced volume, as did the parts of the medial temporal lobe, bilateral temporal poles, and a small cluster in the right lateral prefrontal cortex. Analysis of cortical structure revealed that areas of increased volume in the PWS group were largely driven by greater cortical thickness. Conversely, analysis of myelin content using

  9. Prader-Willi Syndrome due to an Unbalanced de novo Translocation t(15;19)(q12;p13.3).

    Science.gov (United States)

    Dang, Vy; Surampalli, Abhilasha; Manzardo, Ann M; Youn, Stephanie; Butler, Merlin G; Gold, June-Anne; Kimonis, Virginia E

    2016-01-01

    Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic, and behavioral abnormalities. We report the first case of an unbalanced de novo reciprocal translocation of chromosomes 15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the PWS critical chromosome region. Our patient had several typical features of PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet, and food seeking, but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. High-resolution SNP microarray analysis identified an atypical PWS type I deletion in chromosome 15 involving the proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11q13 region, and GABRA5, GABRG3, and OCA2 genes were intact. No deletion of band 19p13.3 was detected; therefore, the patient was not at an increased risk of tumors from the Peutz-Jeghers syndrome associated with a deletion of the STK11 gene. © 2016 S. Karger AG, Basel.

  10. Risk assessment of medically assisted reproduction and advanced maternal ages in the development of Prader-Willi syndrome due to UPD(15)mat.

    Science.gov (United States)

    Matsubara, K; Murakami, N; Fukami, M; Kagami, M; Nagai, T; Ogata, T

    2016-05-01

    Recent studies have suggested that disomic oocyte-mediated uniparental disomy 15 (UPD(15)mat) is increased in patients with Prader-Willi syndrome (PWS) born after medically assisted reproduction (MAR). However, it remains unknown whether the increase is primarily due to MAR procedure itself or advanced maternal childbearing ages as a predisposing factor for the disomic oocyte production. To examine this matter, we studied 122 naturally conceived PWS patients (PWS-NC group) and 13 MAR-conceived patients (PWS-MAR group). The relative frequency of disomic oocyte-mediated UPD(15)mat was significantly higher in PWS-MAR group than in PWS-NC group (7/13 vs 20/122, p = 0.0045), and the maternal childbearing ages were significantly higher in PWS-MAR group than in PWS-NC group [median (range), 38 (26-45) vs 30 (19-42), p = 0.0015]. However, the logistic regression analysis revealed no significant association between the occurrence of disomic oocyte-mediated UPD(15)mat and MAR, after adjusting for childbearing age (p = 0.25). Consistent with this, while the frequency of assisted reproductive technology (ART)-conceived livebirths was higher in the PWS patients than in the Japanese general population (6.4% vs 1.1%, p = 0.00018), the distribution of childbearing ages was significantly skewed to the increased ages in the PWS patients (p < 2.2 × 10(-16) ). These results argue against a positive association of MAR procedure itself with the development of UPD(15)mat. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Dyssynchrony and perinatal psychopathology impact of child disease on parents-child interactions, the paradigm of Prader Willi syndrom.

    Science.gov (United States)

    Viaux-Savelon, Sylvie; Rosenblum, Ouriel; Guedeney, Antoine; Diene, Gwenaelle; Çabal-Berthoumieu, Sophie; Fichaux-Bourin, Pascale; Molinas, Catherine; Faye, Sandy; Valette, Marion; Bascoul, Céline; Cohen, David; Tauber, Maïthé

    2016-11-01

    Infant-mother interaction is a set of bidirectional processes, where the baby is not only affected by the influences of his caregiver, but is also at the origin of considerable modifications. The recent discovery of biological correlates of synchrony during interaction validated its crucial value during child development. Here, we focus on the paradigmatic case of Prader-Willi Syndrome (PWS) where early endocrinal dysfunction is associated with severe hypotonia and early feeding disorder. As a consequence, parent-infant interaction is impaired. In a recent study (Tauber et al., 2017), OXT intranasal infusion was able to partially reverse the feeding phenotype, infant's behavior and brain connectivity. This article details the interaction profile found during feeding in these dyads and their improvement after OXT treatment. Eighteen infants (≤6months) with PWS were recruited and hospitalized 9days in a French reference center for PWS where they were treated with a short course of intranasal OXT. Social withdrawal behavior and mother-infant interaction were assessed on videos of feeding before and after treatment using the Alarm Distress Baby (ADBB) Scale and the Coding Interactive Behavior (CIB) Scale. Raters were blind to treatment status. At baseline, infants with PWS showed hypotonia, low expressiveness of affects, fatigability and poor involvement in the relationship with severe withdrawal. Parents tended to adapt to their child difficulties, but the interaction was perturbed, tense, restricted and frequently intrusive with a forcing component during the feeding situation. After OXT treatment, infants were more alert, less fatigable, more expressive, and had less social withdrawal. They initiated mutual activities and were more engaged in relationships through gaze, behavior, and vocalizations. They had a better global tonicity with better handling. These modifications helped the parents to be more sensitive and the synchrony of the dyad was in a positive

  12. Small mosaic deletion encompassing the snoRNAs and SNURF-SNRPN results in an atypical Prader-Willi syndrome phenotype.

    Science.gov (United States)

    Anderlid, Britt-Marie; Lundin, Johanna; Malmgren, Helena; Lehtihet, Mikael; Nordgren, Ann

    2014-02-01

    Genetic analyses were performed in a male patient with suspected Prader-Willi syndrome who presented with hypogonadism, excessive eating, central obesity, small hands and feet and cognition within the low normal range. However, he had no neonatal hypotonia or feeding problems during infancy. Chromosome analysis showed a normal male karyotype. Further analysis with array-CGH identified a mosaic 847 kb deletion in 15q11-q13, including SNURF-SNRPN, the snoRNA gene clusters SNORD116 (HBII-85), SNORD115, (HBII-52), SNORD109 A and B (HBII-438A and B), SNORD64 (HBII-13), and NPAP1 (C15ORF2). MLPA confirmed the deletion and the results were compatible with a paternal origin. Metaphase-FISH verified the mosaicism with the deletion present in 58% of leukocytes analyzed. Three smaller deletions in this region have previously been reported in patients with Prader-Willi syndrome phenotype. All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome. Furthermore, it examplifies diagnostic difficulties in atypical cases and illustrates the need for additional testing methods when Prader-Willi syndrome is suspected. © 2013 Wiley Periodicals, Inc.

  13. Stress and coping in parents of children with Prader-Willi syndrome: Assessment of the impact of a structured plan of care.

    Science.gov (United States)

    Tvrdik, Tatiana; Mason, Debbie; Dent, Karin M; Thornton, Lisa; Hornton, Sidney N; Viskochil, David H; Stevenson, David A

    2015-05-01

    Hyperphagia, developmental delays, and maladaptive behaviors are common in Prader-Willi syndrome (PWS) likely resulting in heightened parental stress. Objectives were to evaluate stress, describe usefulness of coping behaviors, and assess the impact of a structured Plan of Care (PC) on parents with children with PWS. Parents answered Perceived Stress Scale (PSS-14), Coping Health Inventory for Parents (CHIP), and narrative/demographic surveys. The PC was introduced to a cohort of parents after completion of the PSS-14 and CHIP and re-administered 4-6 month after the introduction of the PC. Higher parental stress (n = 57) was observed compared to the general population, and associated with parent's age, number of children living at home, and child's age and residential setting. "Maintaining family integration, cooperation, and an optimistic definition of the situation" was the most useful coping pattern. Thirty-eight parents answered the PSS-14 and CHIP after the PC. Parental stress decreased after the PC (P = 0.035). Coping behaviors related to "maintaining family integration" increased after the PC (P = 0.042). Women and men preferred different coping patterns before and after the PC. In conclusion, parental stress is increased in PWS, and a PC decreased stress and increased coping behaviors related to family stability for parents with children with PWS. © 2015 Wiley Periodicals, Inc.

  14. Anthropometric adjustments are helpful in the interpretation of BMD and BMC Z-scores of pediatric patients with Prader-Willi syndrome.

    Science.gov (United States)

    Hangartner, T N; Short, D F; Eldar-Geva, T; Hirsch, H J; Tiomkin, M; Zimran, A; Gross-Tsur, V

    2016-12-01

    Anthropometric adjustments of bone measurements are necessary in Prader-Willi syndrome patients to correctly assess the bone status of these patients. This enables physicians to get a more accurate diagnosis of normal versus abnormal bone, allow for early and effective intervention, and achieve better therapeutic results. Bone mineral density (BMD) is decreased in patients with Prader-Willi syndrome (PWS). Because of largely abnormal body height and weight, traditional BMD Z-scores may not provide accurate information in this patient group. The goal of the study was to assess a cohort of individuals with PWS and characterize the development of low bone density based on two adjustment models applied to a dataset of BMD and bone mineral content (BMC) from dual-energy X-ray absorptiometry (DXA) measurements. Fifty-four individuals, aged 5-20 years with genetically confirmed PWS, underwent DXA scans of spine and hip. Thirty-one of them also underwent total body scans. Standard Z-scores were calculated for BMD and BMC of spine and total hip based on race, sex, and age for all patients, as well as of whole body and whole-body less head for those patients with total-body scans. Additional Z-scores were generated based on anthropometric adjustments using weight, height, and percentage body fat and a second model using only weight and height in addition to race, sex, and age. As many PWS patients have abnormal anthropometrics, addition of explanatory variables weight, height, and fat resulted in different bone classifications for many patients. Thus, 25-70 % of overweight patients, previously diagnosed as normal, were subsequently diagnosed as below normal, and 40-60 % of patients with below-normal body height changed from below normal to normal depending on bone parameter. This is the first study to include anthropometric adjustments into the interpretation of BMD and BMC in children and adolescents with PWS. This enables physicians to get a more accurate diagnosis of

  15. Genetic syndromes in the family : child characteristics and parenting stress in Angelman, CHARGE, Cornelia de Lange, Prader-Willi, and Rett syndrome

    NARCIS (Netherlands)

    Wulffaert, Josette

    2010-01-01

    Aim of the dissertation: To expand the knowledge on the behavioural phenotypes, level of parenting stress and the relationship between child characteristics and parenting stress in five genetic syndromes. The included syndromes are Angelman, CHARGE, Cornelia de Lange, Prader-Willi, and Rett

  16. 'A one-sided affair': unilateral pulmonary oedema and the role of cardiac MRI in diagnosing premature coronary artery disease in a patient with Prader-Willi syndrome.

    Science.gov (United States)

    Jabbar, Avais; Khan, Jamal N; Singh, Anvesha; McCann, Gerry P

    2013-05-22

    There is no formal association between premature coronary artery disease (CAD) and Prader-Willi syndrome despite its association with hyperlipidaemia, diabetes mellitus and hypertension. A 36-year-old man with Prader-Willi syndrome presented with acute breathlessness. Inflammatory markers were borderline elevated and chest radiography demonstrated unilateral diffuse alveolar shadowing. Bronchopneumonia was diagnosed and despite treatment with multiple courses of antimicrobial therapy, there was minimal symptomatic and radiographical improvement. A diagnosis of unilateral pulmonary oedema was suspected. Echocardiography was non-diagnostic due to body habitus and coronary angiography was deemed inappropriate due to uncertainty in diagnosis, invasiveness and pre-existing chronic kidney disease. Therefore, cardiac magnetic resonance was performed, confirming severe triple-vessel CAD. This case demonstrates a presentation of heart failure with unilateral chest radiograph changes in a young patient with Prader-Willi syndrome and severe premature CAD detected by multiparametric cardiac magnetic resonance imaging.

  17. Motor performance in Prader-Willi syndrome patients and its potential influence on caregiver’s quality of life

    Directory of Open Access Journals (Sweden)

    Valeria Jia-Yi Chiu

    2017-12-01

    Full Text Available Background Prader-Willi syndrome (PWS is a complex, multisystem genetic disorder characterized by a variety of physical, cognitive, and behavioral impairments. PWS is a unique sarcopenia model characterized by an abnormal increase in body fat mass and a decrease in muscle mass that predisposes patients to reduced physical activity, functional limitations, and disability. These manifestations may require both symptomatic and supportive management, thus negatively influencing their lifelong family caregiver’s quality of life. The aim of this study was to examine the functional motor performance of adults with PWS in Taiwan and to measure the quality of life of their primary family caregivers. Methods The functional motor tests consisted of the following: (1 30-s sit-to-stand test, (2 timed up-and-go test, (3 hand grip and lateral pinch strength tests, and (4 Berg Balance Scale. The World Health Organization Quality of Life-short form (WHOQOL-BREF and the Short-Form 36 Health Survey Questionnaire (SF-36 were used to evaluate health-related quality of life, and the parenting stress index was used to assess the magnitude of stress within the parent-child system. Results The participants included seven adults (two females and five males with genetically confirmed PWS and their respective main caregivers. The mean age of the adults with PWS was 25.28 years; range 18–31 years, SD 5.10; the mean BMI was 29.2 kg/m2, SD 6.43. All adults with PWS showed lower hand grip and lateral pinch strengths, fewer sit-to-stand cycles during the 30-s chair stand test, and greater average time during the timed up-and-go test when compared to the normative data on healthy adults. Balance was negatively correlated with the caregiver’s health concepts of social functioning (rs −0.879, P = 0.009 and with role limitations due to physical problems (rs −0.899, P = 0.006 and emotional problems (rs −0.794, P = 0.033; hand grip strength was negatively correlated

  18. Motor performance in Prader-Willi syndrome patients and its potential influence on caregiver's quality of life.

    Science.gov (United States)

    Chiu, Valeria Jia-Yi; Tsai, Li-Ping; Wei, Jang-Ting; Tzeng, I-Shiang; Wu, Hsin-Chi

    2017-01-01

    Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by a variety of physical, cognitive, and behavioral impairments. PWS is a unique sarcopenia model characterized by an abnormal increase in body fat mass and a decrease in muscle mass that predisposes patients to reduced physical activity, functional limitations, and disability. These manifestations may require both symptomatic and supportive management, thus negatively influencing their lifelong family caregiver's quality of life. The aim of this study was to examine the functional motor performance of adults with PWS in Taiwan and to measure the quality of life of their primary family caregivers. The functional motor tests consisted of the following: (1) 30-s sit-to-stand test, (2) timed up-and-go test, (3) hand grip and lateral pinch strength tests, and (4) Berg Balance Scale. The World Health Organization Quality of Life-short form (WHOQOL-BREF) and the Short-Form 36 Health Survey Questionnaire (SF-36) were used to evaluate health-related quality of life, and the parenting stress index was used to assess the magnitude of stress within the parent-child system. The participants included seven adults (two females and five males) with genetically confirmed PWS and their respective main caregivers. The mean age of the adults with PWS was 25.28 years; range 18-31 years, SD 5.10; the mean BMI was 29.2 kg/m 2 , SD 6.43. All adults with PWS showed lower hand grip and lateral pinch strengths, fewer sit-to-stand cycles during the 30-s chair stand test, and greater average time during the timed up-and-go test when compared to the normative data on healthy adults. Balance was negatively correlated with the caregiver's health concepts of social functioning ( r s -0.879, P  = 0.009) and with role limitations due to physical problems ( r s -0.899, P  = 0.006) and emotional problems ( r s -0.794, P  = 0.033); hand grip strength was negatively correlated with bodily pain ( r s -0.800, P

  19. Individuals with Smith-Magenis syndrome display profound neurodevelopmental behavioral deficiencies and exhibit food-related behaviors equivalent to Prader-Willi syndrome.

    Science.gov (United States)

    Alaimo, Joseph T; Barton, Laura V; Mullegama, Sureni V; Wills, Rachel D; Foster, Rebecca H; Elsea, Sarah H

    2015-12-01

    Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder associated with intellectual disability, sleep disturbances, early onset obesity and vast behavioral deficits. We used the Behavior Problems Inventory-01 to categorize the frequency and severity of behavioral abnormalities in a SMS cohort relative to individuals with intellectual disability of heterogeneous etiology. Self-injurious, stereotyped, and aggressive/destructive behavioral scores indicated that both frequency and severity were significantly higher among individuals with SMS relative to those with intellectual disability. Next, we categorized food behaviors in our SMS cohort across age using the Food Related Problems Questionnaire (FRPQ) and found that problems began to occur in SMS children as early as 5-11 years old, but children 12-18 years old and adults manifested the most severe problems. Furthermore, we evaluated the similarities of SMS adult food-related behaviors to those with intellectual disability and found that SMS adults had more severe behavioral problems. Many neurodevelopmental disorders exhibit syndromic obesity including SMS. Prader-Willi syndrome (PWS) is the most frequent neurodevelopmental disorder with syndromic obesity and has a well-established management and treatment plan. Using the FRPQ we found that SMS adults had similar scores relative to PWS adults. Both syndromes manifest weight gain early in development, and the FRPQ scores highlight specific areas in which behavioral similarities exist, including preoccupation with food, impaired satiety, and negative behavioral responses. SMS food-related behavior treatment paradigms are not as refined as PWS, suggesting that current PWS treatments for prevention of obesity may be beneficial for individuals with SMS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial.

    Science.gov (United States)

    Kuppens, R J; Donze, S H; Hokken-Koelega, A C S

    2016-12-01

    Prader-Willi syndrome (PWS) is known for hyperphagia with impaired satiety and a specific behavioural phenotype with stubbornness, temper tantrums, manipulative and controlling behaviour and obsessive-compulsive features. PWS is associated with hypothalamic and oxytocinergic dysfunction. In humans without PWS, intranasal oxytocin administration had positive effects on social and eating behaviour, and weight balance. To evaluate the effects of intranasal oxytocin compared to placebo administration on social behaviour and hyperphagia in children with PWS. Randomized, double-blind, placebo-controlled, crossover study in a PWS Reference Center in the Netherlands. Crossover intervention with twice daily intranasal oxytocin (dose range 24-48 IU/day) and placebo administration, both during 4 weeks, in 25 children with PWS (aged 6 to 14 years). In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found, but in the 17 children younger than 11 years, parents reported significantly less anger (P = 0·001), sadness (P = 0·005), conflicts (P = 0·010) and food-related behaviour (P = 0·011), and improvement of social behaviour (P = 0·018) during oxytocin treatment compared with placebo. In the eight children older than 11 years, the items happiness (P = 0·039), anger (P = 0·042) and sadness (P = 0·042) were negatively influenced by oxytocin treatment compared to placebo. There were no side effects or adverse events. This randomized, double-blind, placebo-controlled study suggests that intranasal oxytocin administration has beneficial effects on social behaviour and food-related behaviour in children with PWS younger than 11 years of age, but not in those older than 11 years of age. © 2016 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

  1. Prader-Willi syndrome due to an unbalanced de novo translocation [t(15;19)(q12;p13.3)

    Science.gov (United States)

    Dang, Vy; Surampalli, Abhilasha; Manzardo, Ann M; Youn, Stephanie; Butler, Merlin G; Gold, June-Anne; Kimonis, Virginia

    2018-01-01

    Background and Aims Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic and behavioral abnormalities. We report the first case of an unbalanced de-novo reciprocal translocation of chromosome 15 and 19: 45,XY,-15, der (19)t(15;19)(q12;p13.3) resulting in monosomy for the PWS chromosome critical region. We performed high resolution SNP microarray to characterize the breakpoints. Case report Our patient had several typical features for PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet and food seeking but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. Results High resolution SNP microarray analysis identified an atypical PWS Type I deletion of chromosome 15 involving proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11-q13 region and GABRA5, GABRG3 and OCA2 genes were intact. Conclusion We report a case with atypical features for PWS associated with an unbalanced de-novo reciprocal translocation resulting in monosomy for the 15q11.1–15q12 with intact GABRA5, GABRG3 and OCA2 genes. No deletion of 19p13.3 band was detected therefore the patient was not at an increased risk of tumors from Peutz-Jeghers syndrome associated with a deletion of the STK11 gene. PMID:27894106

  2. Trabalho fonoaudiologico em oficina de cozinha em um caso de Prader-Willi Kitchen workshop on the speech-language therapeutic processes of a patient with Prader-Willi syndrome

    Directory of Open Access Journals (Sweden)

    Nathalia Zambotti

    2013-02-01

    Full Text Available TEMA: o objetivo deste estudo é descrever e analisar os efeitos do trabalho fonoaudiológico em Oficina de Cozinha, em processo terapêutico de um paciente portador da síndrome de Prader-Willi. PROCEDIMENTOS: a pesquisa é um estudo de caso de uma criança de 5 anos portadora da Síndrome de Prader-Willi, que apresentava atraso de linguagem e transtornos alimentares. A criança participou durante sete meses do processo terapêutico em Oficina de Cozinha, associado à terapia fonoaudiológica individual. O registro do material clínico foi realizado sistematicamente por escrito, ao longo de cada uma das sessões. RESULTADOS: o caso estudado modificou para melhor seu funcionamento miofuncional oral e de linguagem, como por exemplo: organizando sua função mastigatória e ganhando autonomia da capacidade discursiva. Assumindo a indissociabilidade entre o orgânico e o psíquico, a criança, que apresenta marcas orgânicas advindas da Síndrome, usufruiu de potencialidades da Oficina de Cozinha. CINCLUSÃO: as Oficinas de Cozinha, na condição de dispositivo terapêutico fonoaudiológico, mostrou-se pertinente à articulação biopsíquica no tratamento de pacientes cujas marcas orgânicas determinam limites e especificidades à aquisição e à circulação na linguagem, como são os casos de portadores da síndrome de Prader-Willi.BACKGROUND: describe and analyze the effects of the speech-language work in the Kitchen Workshop on the therapeutic processes of a patient with Prader-Willi syndrome. PROCEDURES: the research is a clinical case study on one child, 5-year old, with Prader-Willi Syndrome, with a delay in speech and feeding problems. The child took part during seven months of the therapeutic process in Kitchen Workshop, associated with individual speech therapy. The clinical material was recorded systematically in writing throughout each one of the sessions. RESULTS: the studied case ameliorated his myo-functional oral functioning and

  3. Trabalho fonoaudiologico em oficina de cozinha em um caso de Prader-Willi Kitchen workshop on the speech-language therapeutic processes of a patient with Prader-Willi syndrome

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    Nathalia Zambotti

    2011-01-01

    Full Text Available TEMA: o objetivo deste estudo é descrever e analisar os efeitos do trabalho fonoaudiológico em Oficina de Cozinha, em processo terapêutico de um paciente portador da síndrome de Prader-Willi. PROCEDIMENTOS: a pesquisa é um estudo de caso de uma criança de 5 anos portadora da Síndrome de Prader-Willi, que apresentava atraso de linguagem e transtornos alimentares. A criança participou durante sete meses do processo terapêutico em Oficina de Cozinha, associado à terapia fonoaudiológica individual. O registro do material clínico foi realizado sistematicamente por escrito, ao longo de cada uma das sessões. RESULTADOS: o caso estudado modificou para melhor seu funcionamento miofuncional oral e de linguagem, como por exemplo: organizando sua função mastigatória e ganhando autonomia da capacidade discursiva. Assumindo a indissociabilidade entre o orgânico e o psíquico, a criança, que apresenta marcas orgânicas advindas da Síndrome, usufruiu de potencialidades da Oficina de Cozinha. CINCLUSÃO: as Oficinas de Cozinha, na condição de dispositivo terapêutico fonoaudiológico, mostrou-se pertinente à articulação biopsíquica no tratamento de pacientes cujas marcas orgânicas determinam limites e especificidades à aquisição e à circulação na linguagem, como são os casos de portadores da síndrome de Prader-Willi.BACKGROUND: describe and analyze the effects of the speech-language work in the Kitchen Workshop on the therapeutic processes of a patient with Prader-Willi syndrome. PROCEDURES: the research is a clinical case study on one child, 5-year old, with Prader-Willi Syndrome, with a delay in speech and feeding problems. The child took part during seven months of the therapeutic process in Kitchen Workshop, associated with individual speech therapy. The clinical material was recorded systematically in writing throughout each one of the sessions. RESULTS: the studied case ameliorated his myo-functional oral functioning and

  4. The effects of Bifidobacterium animalis ssp. lactis B94 on gastrointestinal wellness in adults with Prader-Willi syndrome: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Alyousif, Zainab; Miller, Jennifer L; Sandoval, Mariana Y; MacPherson, Chad W; Nagulesapillai, Varuni; Dahl, Wendy J

    2018-04-27

    Constipation is a frequent problem in adults with Prader-Willi syndrome. Certain probiotics have been shown to improve transit and gastrointestinal symptoms of adults with functional constipation. The aim of this study is to determine the effect of daily consumption of Bifidobacterium animalis ssp. lactis B94 (B. lactis B94) on stool frequency, stool form, and gastrointestinal symptoms in adults with Prader-Willi syndrome. Adults with Prader-Willi syndrome (18-75 years old, n = 36) will be recruited and enrolled in a 20-week, randomized, double-blind, placebo-controlled, crossover study. Study subjects will be randomized to B. lactis B94 or placebo each for a 4-week period, preceded by a 4-week baseline and followed by 4-week washouts. Subjects will complete daily records of stool frequency and stool form (a proxy of transit time). Dietary intake data also will be collected. Stools, one in each period, will be collected for exploratory microbiota analyses. To our knowledge, this is the first randomized controlled trial evaluating the effectiveness of B. lactis in adults with Prader-Willi syndrome. The results of this study will provide evidence of efficacy for future clinical trials in patient populations with constipation. ClinicalTrials.gov ( NCT03277157 ). Registered on 08 September 2017.

  5. Stress, Locus of Control, and Family Cohesion and Adaptability in Parents of Children with Down, Williams, Fragile X, and Prader-Willi Syndromes

    Science.gov (United States)

    Lanfranchi, Silvia; Vianello, Renzo

    2012-01-01

    The present study analyzes differences in parental stress in families of children with Down, Williams, Fragile X, and Prader-Willi syndromes, exploring factors that influence parental stress, such as child's characteristics, parental locus of control, and family cohesion and adaptability. Differences between mothers and fathers are also…

  6. Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial

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    R. J. Kuppens

    2016-11-01

    Full Text Available Abstract Background Patients with Prader-Willi syndrome (PWS have a cognitive impairment. Growth hormone (GH treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Method Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m2/day, both during 1 year. Results Total (TIQ, verbal (VIQ and performance IQ (PIQ did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322. Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Conclusions Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. Trial registration ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

  7. Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial.

    Science.gov (United States)

    Kuppens, R J; Mahabier, E F; Bakker, N E; Siemensma, E P C; Donze, S H; Hokken-Koelega, A C S

    2016-11-16

    Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH) might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m 2 /day), both during 1 year. Total (TIQ), verbal (VIQ) and performance IQ (PIQ) did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322). Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

  8. Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome.

    Science.gov (United States)

    De Waele, Kathleen; Ishkanian, Stacey L; Bogarin, Roberto; Miranda, Charmaine A; Ghatei, Mohammad A; Bloom, Stephen R; Pacaud, Danièle; Chanoine, Jean-Pierre

    2008-10-01

    Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader-Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS. A 56-week prospective, randomized, cross-over trial. Nine subjects with PWS (age 14.6 (10.8-18.9) years, body mass index (BMI) Z-score +1.9 (0.6-3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period. Eight subjects completed the study. Oct caused a decrease in both acylated (-53%) and desacyl (-54%) fasting ghrelin concentrations (P<0.05) but did not significantly affect BMI. Oct had no significant effect on peptide YY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in insulin-like growth factor-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones. Oct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.

  9. Beneficial effects of growth hormone treatment on cognition in children with Prader-Willi syndrome: a randomized controlled trial and longitudinal study.

    Science.gov (United States)

    Siemensma, Elbrich P C; Tummers-de Lind van Wijngaarden, Roderick F A; Festen, Dederieke A M; Troeman, Zyrhea C E; van Alfen-van der Velden, A A E M Janielle; Otten, Barto J; Rotteveel, Joost; Odink, Roelof J H; Bindels-de Heus, G C B Karen; van Leeuwen, Mariette; Haring, Danny A J P; Oostdijk, Wilma; Bocca, Gianni; Mieke Houdijk, E C A; van Trotsenburg, A S Paul; Hoorweg-Nijman, J J Gera; van Wieringen, Hester; Vreuls, René C F M; Jira, Petr E; Schroor, Eelco J; van Pinxteren-Nagler, Evelyn; Willem Pilon, Jan; Lunshof, L Bert; Hokken-Koelega, Anita C S

    2012-07-01

    Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited. Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study during 4 yr of GH treatment. Cognitive functioning was measured biennially by short forms of the WPPSI-R or WISC-R, depending on age. Total IQ (TIQ) score was estimated based on two subtest scores. During the randomized controlled trial, mean sd scores of all subtests and mean TIQ score remained similar compared to baseline in GH-treated children with PWS, whereas in untreated controls mean subtest sd scores and mean TIQ score decreased and became lower compared to baseline. This decline was significant for the Similarities (P = 0.04) and Vocabulary (P = 0.03) subtests. After 4 yr of GH treatment, mean sd scores on the Similarities and Block design subtests were significantly higher than at baseline (P = 0.01 and P = 0.03, respectively), and scores on Vocabulary and TIQ remained similar compared to baseline. At baseline, children with a maternal uniparental disomy had a significantly lower score on the Block design subtest (P = 0.01) but a larger increment on this subtest during 4 yr of GH treatment than children with a deletion. Lower baseline scores correlated significantly with higher increases in Similarities (P = 0.04) and Block design (P deficit had more benefit from GH treatment.

  10. Rigidity in routines and the development of resistance to change in individuals with Prader-Willi syndrome.

    Science.gov (United States)

    Haig, E L; Woodcock, K A

    2017-05-01

    Individuals with Prader-Willi syndrome (PWS) commonly show debilitating resistance to change, which has been linked to cognitive deficits in task switching. Anecdotal reports suggest that exposure to flexibility in routines during development may be beneficial for limiting subsequent resistance to change in people with PWS, which is consistent with a beneficial role of such exposure on the development of task switching, highlighted in typical children. Here, we aim to investigate the development of resistance to change in individuals with PWS and hypothesise that exposure to increased rigidity in routines will be associated with increased subsequent resistance to change. An author-compiled informant report interview and two previously validated questionnaires were administered to the caregivers of 10 individuals with PWS (5-23 years). The interview examined rigidity in routines and resistance to change across life stages defined by easily distinguishable events (before school, during primary school, during secondary school, after school, currently), using open-ended and structured yes/no and 5-point Likert questions. Open-ended data were coded using an author-compiled system. Responses from two additional informants and data from the questionnaires were used to assess inter-informant reliability and concurrent validity of the structured questions. The validity of the interview was supported by acceptable inter-rater reliability of the open-ended coding system and inter-informant reliability, internal consistency and concurrent validity of structured questions. Descriptive analyses of ratings of behaviour change showed a pattern of increasing resistance to change over the life course for the four oldest individuals, who had all been exposed to substantial rigidity in routines before and during primary school. Furthermore, only one individual - currently in primary school - was exposed to very little rigidity in routines before and during primary school, and he had

  11. Microdeletion 15q26.2qter and Microduplication 18q23 in a Patient with Prader-Willi-Like Syndrome: Clinical Findings.

    Science.gov (United States)

    Dello Russo, Patrizia; Demori, Eliana; Sechi, Annalisa; Passon, Nadia; Romagno, Daniela; Gnan, Chiara; Zoratti, Raffaele; Damante, Giuseppe

    2016-01-01

    The small interstitial deletion in the long arm of chromosome 15 causing Prader-Willi/Angelman syndrome is well known, whereas cases that report terminal deletions in 15q in association with the Prader-Willi-like phenotype are very rare. By using GTG-banding analysis, metaphase FISH, MLPA analysis, and genome-wide array CGH, we detected an unbalanced translocation involving a microdeletion of the distal part of 15q and a microduplication of the distal part of 18q. The unbalanced translocation was found in a boy that was referred with clinical suspicion of Prader-Willi syndrome. In the 15q-deleted region, 23 genes have been identified, and 13 of them are included in the OMIM database. Among these, the deleted IGFR1, MEF2A, CHSY1, and TM2D3 genes could contribute to the patient's phenotype. Seven genes are included in the duplicated chromosome segment 18q, but only one (CTDP1) is present in the OMIM database. We suggest that the deleted chromosome segment 15q26.2qter may be responsible for the phenotype of our case and may also be a candidate locus of Prader-Willi-like syndrome. © 2016 S. Karger AG, Basel.

  12. Genetic factors in human sleep disorders with special reference to Norrie disease, Prader-Willi syndrome and Moebius syndrome.

    Science.gov (United States)

    Parkes, J D

    1999-06-01

    Sleep-wake problems are common in specific inborn errors of metabolism and structure of the central nervous system. Psychological factors, behavioural difficulties, metabolic disturbances, and widespread rather than focal damage to the nervous system are present in many of these diseases and all influence the sleep-wake cycle. However, a number of conditions cause relatively focal damage to the neuroanatomical substrate of sleeping and waking. These include fatal familial insomnia, with involvement of the prion protein gene on chromosome 20, Norrie disease, the Prader-Willi syndrome and the Moebius syndrome. The last three important conditions, although rare, are considered in detail in this review. They result in sensory deprivation, hypothalamic and mid-brain damage, and involve the X-chromosome, chromosome 15, and chromosome 13, respectively. These conditions cause a wide variety of sleep disturbance, including parasomnias, daytime sleepiness, and a condition like cataplexy. The place of the relevant gene products in normal sleep regulation needs further exploration.

  13. Clinical-neurologic, cytogenetic and molecular aspects of the Prader-Willi and Angelman Syndromes Aspectos clínico-neurológicos, citogenéticos e moleculares das síndromes de Prader-Willi e Angelman

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    João M. de Pina-Neto

    1997-06-01

    Full Text Available The Prader-Willi syndrome (PWS and the Angelman syndrome (AS are human neurogenetic disorders involving the imprinting mechanism, at the 15q11-13 chromosome region. The predominant genetic defects in PW are 15q 11-13 deletions of paternal origin and maternal chromosome 15 uniparental disomy. In contrast, maternal deletions and paternal chromosome 15 uniparental disomy are associated with a different neurogenetic disorder, the AS. In both disorders, these mutations are associated with parent-of-origin specific methylation at several 15q 11-13 loci. We studied 5 patients suspect of PWS and 4 patients suspect of AS who were referred to the Medical Genetics Unit at the University Hospital of Medical School from Ribeirão Preto. Our objective was to establish the correct clinical and etiological diagnosis in these cases. We used conventional cytogenetics, methylation analysis with the probe KB 17 (CpG island of the SNRPN gene by Southern blotting after digestion with the Xba I and Not I restriction enzymes. We studied in patients and their parents the segregation of the (CAn repeats polymorphisms by PCR, using the primers 196 and IR4-3R. All the patients had normal conventional cytogenetical analysis. We confirmed 3 cases of PWS: one by de novo deletion, one by maternal chromosome 15 uniparental disomy and one case with no defined cause determined by the used primers. We confirmed 2 cases of AS, caused by de novo deletion at the 15q 11-13 region, and one case with normal molecular analysis but with strong clinical characteristics.A síndrome de Prader-Willi (SPW e a síndrome de Angelman (SA são doenças neurogenéticas consideradas como exemplos do fenômeno de imprinting em seres humanos, estando relacionadas com alterações envolvendo a região cromossômica 15q11-13. As alterações genéticas predominantes na SPW são deleções na região 15q 11-13 de origem paterna e dissomia uniparental materna. Na SA encontra-se deleções na região 15q

  14. Chromosome breakage in Prader-Willi and Angelman syndrome deletions may involve recombination between a repeat at the proximal and distal breakpoints

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    Amos-Landgraf J.; Nicholls, R.D. [Case Western Reserve Univ., Cleveland, OH (United States); Gottlieb, W. [Univ. of Florida, Gainesville, FL (United States)] [and others

    1994-09-01

    Prader-Willi (PWS) and Angelman (AS) syndromes most commonly arise from large deletions of 15q11-q13. Deletions in PWS are paternal in origin, while those in AS are maternal in origin, clearly demonstrating genomic imprinting in these clinically distinct neurobehavioural disorders. In at least 90% of PWS and AS deletion patients, the same 4 Mb region within 15q11-q13 is deleted with breakpoints clustering in single YAC clones at the proximal and distal ends. To study the mechanism of chromosome breakage in PWS and AS, we have previously isolated 25 independent clones from these three YACs using Alu-vector PCR. Four clones were selected that appear to detect a low copy repeat that is located in the proximal and distal breakpoint regions of chromosome 15q11-q13. Three clones detect the same 4 HindIII bands in genomic DNA, all from 15q11-q13, with differing intensities for the probes located at the proximal or distal breakpoints region, respectively. This suggests that these probes detect related members of a low-copy repeat at either location. Moreover, the 254RL2 probe detects a novel HindIII band in two unrelated PWS deletion patients, suggesting that this may represent a breakpoint fragment, with recombination occurring within a similar interval in both patients. A fourth clone, 318RL3 detects 5 bands in HindIII-digested genomic DNA, all from 15q11-q13. This YAC endclone itself is not deleted in PWS and AS deletion patients, as seen by an invariant strong band. Two other strong bands are variably intact or deleted in different PWS or AS deletion patients, suggesting a relationship of this sequence to the breakpoints. Moreover, PCR using 318RL3 primers from the distal 93C9 YAC led to the isolation of a related clone with 96% identity, demonstrating the existence of a low-copy repeat with members close to the proximal and distal breakpoints. Taken together, our data suggest a complex, low-copy repeat with members at both the proximal and distal boundaries.

  15. Molecular breakpoint cloning and gene expression studies of a novel translocation t(4;15(q27;q11.2 associated with Prader-Willi syndrome

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    Slater Howard R

    2005-05-01

    Full Text Available Abstract Background Prader-Willi syndrome (MIM #176270; PWS is caused by lack of the paternally-derived copies, or their expression, of multiple genes in a 4 Mb region on chromosome 15q11.2. Known mechanisms include large deletions, maternal uniparental disomy or mutations involving the imprinting center. De novo balanced reciprocal translocations in 5 reported individuals had breakpoints clustering in SNRPN intron 2 or exon 20/intron 20. To further dissect the PWS phenotype and define the minimal critical region for PWS features, we have studied a 22 year old male with a milder PWS phenotype and a de novo translocation t(4;15(q27;q11.2. Methods We used metaphase FISH to narrow the breakpoint region and molecular analyses to map the breakpoints on both chromosomes at the nucleotide level. The expression of genes on chromosome 15 on both sides of the breakpoint was determined by RT-PCR analyses. Results Pertinent clinical features include neonatal hypotonia with feeding difficulties, hypogonadism, short stature, late-onset obesity, learning difficulties, abnormal social behavior and marked tolerance to pain, as well as sticky saliva and narcolepsy. Relative macrocephaly and facial features are not typical for PWS. The translocation breakpoints were identified within SNRPN intron 17 and intron 10 of a spliced non-coding transcript in band 4q27. LINE and SINE sequences at the exchange points may have contributed to the translocation event. By RT-PCR of lymphoblasts and fibroblasts, we find that upstream SNURF/SNRPN exons and snoRNAs HBII-437 and HBII-13 are expressed, but the downstream snoRNAs PWCR1/HBII-85 and HBII-438A/B snoRNAs are not. Conclusion As part of the PWCR1/HBII-85 snoRNA cluster is highly conserved between human and mice, while no copy of HBII-438 has been found in mouse, we conclude that PWCR1/HBII-85 snoRNAs is likely to play a major role in the PWS- phenotype.

  16. Prader-Willi Disease: A Case Study.

    Science.gov (United States)

    Forbus, William R., III

    A case study focuses on the characteristics and physical management of a 15-year-old with Prader-Willi Syndrome, a birth defect associated with hypotonia, insatiable appetite, hypogonadism, central nervous system dysfunction, and abnormal growth and development . A literature review addresses studies dealing with behavior modification of obesity…

  17. Medical, psychological and social features in a large cohort of adults with Prader-Willi syndrome: experience from a dedicated centre in France.

    Science.gov (United States)

    Laurier, V; Lapeyrade, A; Copet, P; Demeer, G; Silvie, M; Bieth, E; Coupaye, M; Poitou, C; Lorenzini, F; Labrousse, F; Molinas, C; Tauber, M; Thuilleaux, D; Jauregi, J

    2015-05-01

    Prader-Willi syndrome (PWS) is a developmental genetic disorder characterised by a variable expression of medical, cognitive and behavioural symptoms. In adulthood, the prevalence and severity of these symptoms determine the quality of life of the affected persons. Because of their rare disease condition, data on health and social problems in adults with PWS are scarce. In this research, we present medical, psychological and social features of a large cohort of adults admitted to a specialised PWS centre in France and analyse the differences according to genotype, gender and age. Data from 154 patients (68 men/86 women), with a median age of 27 years (range 16-54), were collected during their stay in our centre. Clinical histories were completed using information from parents or main caregivers, and the same medical team performed the diagnosis of different clinical conditions. Statistical analyses were performed to determine the influence of factors such as genotype, age or gender. Paternal deletion genotype was the most frequent (65%) at all ages. Most patients had mild or moderate intellectual disability (87%). Only 30% had studied beyond primary school and 70% were in some special educational or working programme. Most of them lived in the family home (57%). The most prevalent somatic comorbidities were scoliosis (78%), respiratory problems (75%), dermatological lesions (50%), hyperlipidaemia (35%), hypothyroidism (26%), Type 2 diabetes mellitus (25%) and lymph oedema (22%). Some form of psychotropic treatment was prescribed in 58% of subjects, and sex hormones in 43%. Patients with deletion had a higher body mass index (44 vs. 38.9 kg/m(2)) and displayed higher frequency of sleep apnoeas. Non-deletion patients received insulin treatment (19% vs. 4%) and antipsychotic treatment (54.8% vs. 32.7%) more frequently. No difference was observed in the prevalence of Type 2 diabetes between the two genotype groups. Patients >27 years of age had a higher rate of

  18. Escoliosis y síndrome de Prader-Willi: a propósito de 5 casos intervenidos quirúrgicamente Escoliose e síndrome de Prader-Willi: análise de cinco casos tratados cirurgicamente Scoliosis and Prader-Willi syndrome: review of five cases treated surgically

    Directory of Open Access Journals (Sweden)

    Jose Grass Pedrals

    2012-06-01

    em dois (14,3% e cifose depois da instrumentação em um caso (7,1%. Não foram verificadas complicações graves. CONCLUSÕES: Mesmo que a literatura mostre autores pouco inclinados a indicar cirurgia nesse tipo de pacientes, por causa da elevada taxa de complicações graves, a ausência dessas complicações em nossa prática valida os mesmos critérios cirúrgicos da escoliose idiopática.OBJECTIVE: Analyze the results and complications of scoliosis surgery in patients with Prader-Willi syndrome to verify if this kind of treatment is justified. METHODS: Retrospective analysis of clinical records and radiographs of five patients with Prader-Willi syndrome treated at the Department of Scoliosis between 2005 and 2010. RESULTS: The average age of patients at the first visit was 3.6 years. The average scoliosis was 61°, which increased to 65° at the time of surgery. The average number of surgeries performed per patient was 2.8, reaching an average correction of 35%. The reasons for re-interventions were correction loss in 4 cases (28.5%, loosening of hooks in two cases (14.3%, and kyphosis after instrumentation in one case (7.1%. There were no serious complications. CONCLUSIONS: Even though the literature shows authors unwilling to indicate surgery in such patients because of the high rate of severe complications, the absence of these complications in our practice validates the use of the same surgical criteria of idiopathic scoliosis.

  19. Changes in body composition, blood lipid profile, and growth factor hormone in a patient with Prader-willi syndrome during 24 weeks of complex exercise: a single case study.

    Science.gov (United States)

    Joung, Hee Joung; Lim, In Soo

    2018-03-30

    Prader-Willi syndrome (PWS) is a genetic disorder characterized by excessive appetite with progressive obesity and growth hormone (GH) deficiency. Excessive eating causes progressive obesity with increased risk of morbidities and mortality. Although GH treatment has beneficial effects on patients with PWS, adverse events have occurred during GH treatment. Exercise potentially has a positive effect on obesity management. The purpose of this research was to examine the effects of 24-week complex exercise program on changes in body composition, blood lipid profiles, and growth factor hormone levels in a patient with PWS. The case study participant was a 23-year-old man with PWS who also had type II diabetes mellitus because of extreme obesity. Complex exercises, including strength and aerobic exercises, were conducted 5 times one week for 60 minutes per session, over 24 weeks. Blood sampling was conducted five times: before and at 8, 16, 20, and 24 weeks after commencement of the exercise program. Weight, fat mass, triglycerides/high-density lipoprotein (TG/HDL) ratio, mean blood glucose, and GH decreased after training. Blood insulin and insulin-like growth factor (IGF-1) levels increased after training. At 15 and 20 weeks, insulin injection was discontinued. Insulin levels increased and average blood glucose decreased to normal levels; IGF-1 increased continuously during the 24-week exercise program. Conclusion] Twenty-four weeks of complex exercises had a positive effect on obesity and diabetes in the patient with PWS. Therefore, long-period complex exercises might be an effective intervention for improvement of metabolic factors in PWS patients. ©2018 The Korean Society for Exercise Nutrition.

  20. A Paternally Inherited Duplication in the Prader-Willi/Angelman Syndrome Critical Region: A Case and Family Study

    Science.gov (United States)

    Veltman, Marijcke W. M.; Thompson, Russell J.; Craig, Ellen E.; Dennis, Nicholas R.; Roberts, Sian E.; Moore, Vanessa; Brown, Josie A.; Bolton, Patrick F.

    2005-01-01

    The Prader-Willi/Angelman Critical Region (PWACR; Chromosome 15q11-13) is of interest as a potential locus for genes conferring susceptibility to autism spectrum disorders (ASD). This report describes a female proband referred for evaluation of a possible ASD. Genetic analyses indicated that the proband, her father and one of her sisters, carried…

  1. The heterogeneity of craniofacial morphology in Prader-Willi patients.

    Science.gov (United States)

    Belengeanu, D; Bratu, Cristina; Stoian, Monica; Motoc, A; Ormerod, Eli; Podariu, Angela Codruţa; Farcaş, Simona; Andreescu, Nicoleta

    2012-01-01

    Prader-Willi syndrome is a complex genetic disorder with narrow spectrum of facial phenotypic signs, which make the clinical diagnosis difficult in some cases. There are several reports describing the craniofacial appearance of Prader-Willi patients, but there are only a few cephalometric studies for these patients. In this study were included 18 patients with Prader-Willi syndrome and a control group of 18 subjects of both sexes selected based on specific criteria. The cephalometric radiographs of the patients were taken using the standardized technique with centric teeth in occlusion and lips in relaxed position. Angular, horizontal and linear measurements were analyzed for the study group and for the control group. We established that in Prader-Willi patients, there is a decrease of the majority of parameters but the degree of this reduction varies widely between patients and clinically typical facies not always have smaller measurements which can be found in an unusual facies. Facial dysmorphism in Prader-Willi patients varies a group ranging from miss proportions that do not alter the facial architecture as regard of facial typology, skeletal class and pattern of development to a severe disturbance of those. There is a degree of clinical heterogeneity between subjects with Prader-Willi syndrome on clinical evaluation and cephalometric study confirms the heterogeneity for this patients. Because the identification of smaller dimensions for majority of parameters in children and adults, the possibility of developmental delay or growth retardation delay can be excluded. These findings are important for the orthodontist for optimum timing of orthodontic management of patients with Prader-Willi syndrome.

  2. Psychiatric Illness in a Cohort of Adults with Prader-Willi Syndrome

    Science.gov (United States)

    Sinnema, Margje; Boer, Harm; Collin, Philippe; Maaskant, Marian A.; van Roozendaal, Kees E. P.; Schrander-Stumpel, Constance T. R. M.; Curfs, Leopold M. G.

    2011-01-01

    Previous studies have suggested an association between PWS and comorbid psychiatric illness. Data on prevalence rates of psychopathology is still scarce. This paper describes a large-scale, systematic study investigating the prevalence of psychiatric illness in a Dutch adult PWS cohort. One hundred and two individuals were screened for psychiatric…

  3. Prader-Willi syndrome and Tay-Sachs disease in association with mixed maternal uniparental isodisomy and heterodisomy 15 in a girl who also had isochromosome Xq.

    Science.gov (United States)

    Zeesman, Susan; McCready, Elizabeth; Sadikovic, Bekim; Nowaczyk, Małgorzata Jm

    2015-01-01

    Malsegregation of chromosomes during reproduction can result in uniparental disomy when associated with trisomy rescue, monosomy rescue or gamete complementation. Pathogenicity stemming from uniparental disomy in liveborns results from imprinting disorders or autozygosity for autosomal recessive disorders. We report on a girl with Prader-Willi syndrome and Tay-Sachs disease resulting from maternal uniparental disomy of chromosome 15. The child also had an isochromosome Xq. To further characterize the etiology of the aberrant chromosome 15 and the isochromosome Xq, SNP loci from both chromosomes were assessed in the proband and parents, and genome-wide DNA methylation analysis was performed. SNP and DNA methylation analysis confirmed maternal uniparental heterodisomy around the Prader-Willi locus, while the region around the HEXA locus showed maternal uniparental isodisomy. This result is consistent with trisomy rescue of a maternal meiosis l error in a chromosome 15 with two meiotic recombinations. SNP analysis of the X chromosomes is consistent with a maternal origin for the isochromosome. © 2014 Wiley Periodicals, Inc.

  4. Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitor as an Add-on Drug to GLP-1 Receptor Agonists for Glycemic Control of a Patient with Prader-Willi Syndrome: A Case Report.

    Science.gov (United States)

    Horikawa, Yukio; Enya, Mayumi; Komagata, Makie; Hashimoto, Ken-Ichi; Kagami, Masayo; Fukami, Maki; Takeda, Jun

    2018-02-01

    Diabetes patients with Prader-Willi syndrome (PWS) are obese because of hyperphagia; weight control by dietary modification and medicine is required for glycemic control. There are several recent reports showing the effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in PWS. A 36-year-old Japanese male patient was diagnosed with PWS at 10 years of age. At age 16 years, he was diagnosed with diabetes and began to take several kinds of oral hypoglycemic agents. At age 29 years, his BMI was 39.1 kg/m 2 and he was referred to our department for diabetes and obesity treatment. In the present case, the HbA1c was not improved by GLP-1RAs despite a 28-kg BW reduction, which included a 9-kg loss of muscle. Apprehensive of further loss of muscle mass, basal insulin of insulin glargine was administered in addition to GLP-1RAs. Immediately after the addition of tofogliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, the patient's HbA1c decreased dramatically with only about an additional 3% BW reduction. We note an improvement in our case of lipid deposition in the pancreas confirmed by abdominal CT after the improvement of HbA1c. It is unknown whether this improvement of fatty pancreas was a cause or an effect of the improved glycemic control in the present case. This finding clearly supports the effectiveness of combining SGLT2 inhibitors with GLP-1RAs for treatment of patients with PWS and non-alcoholic fatty pancreas disease.

  5. The behavioral impact of growth hormone treatment for children and adolescents with Prader-Willi syndrome: a 2-year, controlled study.

    Science.gov (United States)

    Whitman, Barbara Y; Myers, Susan; Carrel, Aaron; Allen, David

    2002-02-01

    Prader-Willi syndrome (PWS) is characterized by obesity, hypotonia, hypogonadism, hyperphagia, short stature, and a neurobehavioral profile that includes cognitive deficits, learning problems, and behavioral difficulties that increase in both quantity and severity over time. PWS results from an alteration in the molecular composition of a critical region of C#15q. Morbid obesity resulting from hyperphagia is amplified by decreased energy expenditure and reduced physical activity. The hyperphagia has proven refractory to all psychopharmocologic intervention; the behavioral components are equally resistant to psychotropic intervention. PWS patients' body composition resembles that of individuals with growth hormone (GH) deficiency, including short stature and reduced lean body mass with concomitant increased fat mass. We hypothesized that GH administration to children with PWS, in addition to stimulating linear growth, would improve body composition, increase energy expenditure and fat utilization, and improve muscle strength, physical agility, and pulmonary function. Two recent reports from this study document significant positive effects of GH treatment on these children's physical parameters measured in a 2-year, controlled study. However, the behavioral impact of GH treatment in this population remains incompletely described. A psychosocial burden, including emotional, behavioral, and cognitive disturbances associated with short stature, has been previously described in a non-PWS population with GH deficiency and idiopathic short stature. An impaired quality of life and psychosocial status is also documented in otherwise normal adults with GH deficiency. In both populations, growth hormone replacement therapy (GHRT) is reported to improve alertness, activity level, endurance, irritability, tendency to worry, and extroversion resulting in better personal relationships with fewer conflicts. This report focuses on that portion of the study investigating the

  6. Special Care Dentistry in a Patient with Prader-Willi Syndrome through the Use of Atraumatic Restorative Treatment under General Anesthesia.

    Science.gov (United States)

    Roman-Torres, Caio Vinícius Gonçalves; Kussaba, Sérgio Takashi; Bantim, Yasmin Comoti Vita; de Oliveira, Roberta de Barros Antunes Almeida

    2017-01-01

    Prader-Willi syndrome described in 1956 has a genetic origin, affecting both genders, varying in presence and intensity from individual to individual. A precocious diagnosis, before the manifestation of symptoms, has brought some improvement in the quality of life of the carriers in the last years. The objective of this case report was to describe the treatment realized in a 3-year-old boy who presented grade II obesity, difficulty of locomotion, hypotonia, and history of cardiopathy. A dental treatment under general anesthesia was defined, allowing an oral adequation in a single section, in which it was planned the extraction of the element 74 and atraumatic restorative treatment (ART) technique in the other teeth. The precocious intervention in this 3-year-old patient by the therapy realized with ART under general anesthesia was done with success, avoiding unnecessary extractions, preserving dental elements, and maintaining the oral cavity in adequate function.

  7. An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism.

    Science.gov (United States)

    Meziane, Hamid; Schaller, Fabienne; Bauer, Sylvian; Villard, Claude; Matarazzo, Valery; Riet, Fabrice; Guillon, Gilles; Lafitte, Daniel; Desarmenien, Michel G; Tauber, Maithé; Muscatelli, Françoise

    2015-07-15

    Mutations of MAGEL2 have been reported in patients presenting with autism, and loss of MAGEL2 is also associated with Prader-Willi syndrome, a neurodevelopmental genetic disorder. This study aimed to determine the behavioral phenotype of Magel2-deficient adult mice, to characterize the central oxytocin (OT) system of these mutant mice, and to test the curative effect of a peripheral OT treatment just after birth. We assessed the social and cognitive behavior of Magel2-deficient mice, analyzed the OT system of mutant mice treated or not by a postnatal administration of OT, and determined the effect of this treatment on the brain. Magel2 inactivation induces a deficit in social recognition and social interaction and a reduced learning ability in adult male mice. In these mice, we reveal anatomical and functional modifications of the OT system and show that these defects change from birth to adulthood. Daily administration of OT in the first postnatal week was sufficient to prevent deficits in social behavior and learning abilities in adult mutant male mice. We show that this OT treatment partly restores a normal OT system. Thus, we report that an alteration of the OT system around birth has long-term consequences on behavior and on cognition. Importantly, an acute OT treatment of Magel2-deficient pups has a curative effect. Our study reveals that OT plays a crucial role in setting social behaviors during a period just after birth. An early OT treatment in this critical period could be a novel therapeutic approach for the treatment of neurodevelopmental disorders such as Prader-Willi syndrome and autism. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Síndrome de Prader Willi: Presentación clínica de dos pacientes y revisión de la literatura Prader-Willi syndrome: Clinical report of two patients and literature review

    Directory of Open Access Journals (Sweden)

    Nuris Rodríguez Vargas

    2006-03-01

    Full Text Available El síndrome de Prader Willi es una afección de niños y jóvenes caracterizada por obesidad, baja talla, oligofrenia, llanto débil o gemido, hipoplasia de los escrotos, testículos no descendidos, entre otros. En la pubertad se asocia a un desarrollo demorado e incompleto y a la aparición de diabetes mellitus y elevada excreción de gonadotropina. Presentamos en este trabajo a dos pacientes que cumplen estos criterios clínicos y que fueron estudiados en el Policlínico Docente «19 de Abril». Se realiza una breve revisión bibliográfica del síndrome.

  9. De novo unbalanced translocations in Prader-Willi and Angelman syndrome might be the reciprocal product of inv dup(15s.

    Directory of Open Access Journals (Sweden)

    Elena Rossi

    Full Text Available The 15q11-q13 region is characterized by high instability, caused by the presence of several paralogous segmental duplications. Although most mechanisms dealing with cryptic deletions and amplifications have been at least partly characterized, little is known about the rare translocations involving this region. We characterized at the molecular level five unbalanced translocations, including a jumping one, having most of 15q transposed to the end of another chromosome, whereas the der(15(pter->q11-q13 was missing. Imbalances were associated either with Prader-Willi or Angelman syndrome. Array-CGH demonstrated the absence of any copy number changes in the recipient chromosome in three cases, while one carried a cryptic terminal deletion and another a large terminal deletion, already diagnosed by classical cytogenetics. We cloned the breakpoint junctions in two cases, whereas cloning was impaired by complex regional genomic architecture and mosaicism in the others. Our results strongly indicate that some of our translocations originated through a prezygotic/postzygotic two-hit mechanism starting with the formation of an acentric 15qter->q1::q1->qter representing the reciprocal product of the inv dup(15 supernumerary marker chromosome. An embryo with such an acentric chromosome plus a normal chromosome 15 inherited from the other parent could survive only if partial trisomy 15 rescue would occur through elimination of part of the acentric chromosome, stabilization of the remaining portion with telomere capture, and formation of a derivative chromosome. All these events likely do not happen concurrently in a single cell but are rather the result of successive stabilization attempts occurring in different cells of which only the fittest will finally survive. Accordingly, jumping translocations might represent successful rescue attempts in different cells rather than transfer of the same 15q portion to different chromosomes. We also hypothesize that

  10. Early diagnosis and care is achieved but should be improved in infants with Prader-Willi syndrome.

    Science.gov (United States)

    Bar, Céline; Diene, Gwenaelle; Molinas, Catherine; Bieth, Eric; Casper, Charlotte; Tauber, Maithé

    2017-06-28

    PWS is a severe neurodevelopmental genetic disorder now usually diagnosed in the neonatal period from hypotonia and feeding difficulties. Our study analyzed the birth incidence and care of infants with early diagnosis. Data were collected on 61 infants with a molecular diagnosis of PWS born in 2012 and 2013 in France. Thirty-eight infants with PWS were born in 2013. The median age at diagnosis was 18 days. Birth incidence calculated for 2013 was 1/21,000 births. No case was diagnosed prenatally, despite 9 amniocenteses, including 4 for polyhydramnios. Five infants had delayed diagnosis, after 3 months of life. For 2 of them, the diagnosis was not suspected at birth and for 3, FISH analysis in the neonatal period was normal, with no further molecular studies. Ninety-three percent of the neonates were hospitalized, and 84% needed nasogastric tube feeding for a median of 38 days. Swallowing assessment was performed for 45%, at a median age of 10 days. Physiotherapy was started for 76% during hospitalization. Eighty percent of those diagnosed within the first 3 months were seen by a pediatric endocrinologist within the first week of life. Our study is the first to assess the birth incidence of PWS in France, at 1/21,000 births. Some prenatal or neonatal cases remain undiagnosed because of unrecognized clinical signs and the inappropriate choice of the initial molecular test. We also underscore the need to optimize neonatal care of infants with PWS.

  11. A Comparative Study of Educational Provision for Children with Neurogenetic Syndromes: Parent and Teacher Survey

    Science.gov (United States)

    Reilly, C.; Senior, J.; Murtagh, L.

    2015-01-01

    Background: A number of neurogenetic syndromes have a high association with special educational needs including fragile X syndrome (FXS), Prader-Willi syndrome (PWS), Williams syndrome (WS) and Velo-Cardio-Facial syndrome (VCFS). There is a paucity of research on educational provision for children affected by these syndromes. Method: Parents…

  12. Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis

    Science.gov (United States)

    Mejlachowicz, Dan; Nolent, Flora; Maluenda, Jérome; Ranjatoelina-Randrianaivo, Hanitra; Giuliano, Fabienne; Gut, Ivo; Sternberg, Damien; Laquerrière, Annie; Melki, Judith

    2015-01-01

    Arthrogryposis multiplex congenita (AMC) is characterized by the presence of multiple joint contractures resulting from reduced or absent fetal movement. Here, we report two unrelated families affected by lethal AMC. By genetic mapping and whole-exome sequencing in a multiplex family, a heterozygous truncating MAGEL2 mutation leading to frameshift and a premature stop codon (c.1996delC, p.Gln666Serfs∗36) and inherited from the father was identified in the probands. In another family, a distinct heterozygous truncating mutation leading to frameshift (c.2118delT, p.Leu708Trpfs∗7) and occurring de novo on the paternal allele of MAGEL2 was identified in the affected individual. In both families, RNA analysis identified the mutated paternal MAGEL2 transcripts only in affected individuals. MAGEL2 is one of the paternally expressed genes within the Prader-Willi syndrome (PWS) locus. PWS is associated with, to varying extents, reduced fetal mobility, severe infantile hypotonia, childhood-onset obesity, hypogonadism, and intellectual disability. MAGEL2 mutations have been recently reported in affected individuals with features resembling PWS and called Schaaf-Yang syndrome. Here, we show that paternal MAGEL2 mutations are also responsible for lethal AMC, recapitulating the clinical spectrum of PWS and suggesting that MAGEL2 is a PWS-determining gene. PMID:26365340

  13. Structural rearrangements of chromosome 15 satellites resulting in Prader-Willi syndrome suggest a complex mechanism for uniparental disomy

    Energy Technology Data Exchange (ETDEWEB)

    Toth-Fijel, S.; Gunter, K.; Olson, S. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1994-09-01

    We report two cases of PWS in which there was abnormal meiosis I segregation of chromosome 15 following a rare translocation event between the heteromorphic satellite regions of chromosomes 14 and 15 and an apparent meiotic recombination in the unstable region of 15q11.2. PWS and normal appearing chromosomes in case one prompted a chromosome 15 origin analysis. PCR analysis indicated maternal isodisomy for the long arm of chromosome. However, only one chromosome 15 had short arm heteromorphisms consistent with either paternal or maternal inheritance. VNTR DNA analysis and heteromorphism data suggest that a maternal de novo translocation between chromosome 14 and 15 occurred prior to meiosis I. This was followed by recombination between D15Z1 and D15S11 and subsequent meiosis I nondisjunction. Proband and maternal karyotype display a distamycin A-DAPI positive region on the chromosome 14 homolog involved in the translocation. Fluorescent in situ hybridization (FISH) analyses of ONCOR probes D15S11, SNRPN, D15S11 and GABRB 3 were normal, consistent with the molecular data. Case two received a Robertsonian translocation t(14;15)(p13;p13) of maternal origin. Chromosome analysis revealed a meiosis I error producing UPD. FISH analysis of the proband and parents showed normal hybridization of ONCOR probes D15Z1, D15S11, SNRPN, D15S10 and GABRB3. In both cases the PWS probands received a structurally altered chromosome 15 that had rearranged with chromosome 14 prior to meiosis. If proper meiotic segregation is dependent on the resolution of chiasmata and/or the binding to chromosome-specific spindle fibers, then it may be possible that rearrangements of pericentric or unstable regions of the genome disrupt normal disjunction and lead to uniparental disomy.

  14. Postural adaptations to long-term training in Prader-Willi patients

    Science.gov (United States)

    2011-01-01

    Background Improving balance and reducing risk of falls is a relevant issue in Prader-Willi Syndrome (PWS). The present study aims to quantify the effect of a mixed training program on balance in patients with PWS. Methods Eleven adult PWS patients (mean age: 33.8 ± 4.3 years; mean BMI: 43.3 ± 5.9 Kg/m2) attended a 2-week training program including balance exercises during their hospital stay. At discharge, Group 1 (6 patients) continued the same exercises at home for 6 months, while Group 2 (5 patients) quitted the program. In both groups, a low-calorie, well-balanced diet of 1.200 kcal/day was advised. They were assessed at admission (PRE), after 2 weeks (POST1) and at 6-month (POST2). The assessment consisted of a clinical examination, video recording and 60-second postural evaluation on a force platform. Range of center of pressure (CoP) displacement in the antero-posterior direction (RANGEAP index) and the medio-lateral direction (RANGEML index) and its total trajectory length were computed. Results At POST1, no significant changes in all of the postural parameters were observed. At completion of the home program (POST2), the postural assessment did not reveal significant modifications. No changes in BMI were observed in PWS at POST2. Conclusions Our results showed that a long-term mixed, but predominantly home-based training on PWS individuals was not effective in improving balance capacity. Possible causes of the lack of effectiveness of our intervention include lack of training specificity, an inadequate dose of exercise, an underestimation of the neural and sensory component in planning rehabilitation exercise and failed body weight reduction during the training. Also, the physiology of balance instability in these patients may possibly compose a complex puzzle not affected by our exercise training, mainly targeting muscle weakness. PMID:21575153

  15. Personality profiles of youngsters with Velo-Cardio-Facial Syndrome

    NARCIS (Netherlands)

    Prinzie, P.; Swillen, A.; Vogels, A.; Kockuyt, V.; Curfs, L.M.G.; Haselager, G.J.T.; Hellinckx, W.; Devriendt, K.; Onghena, P.; Lieshout, C.F.M. van; Fryns, J.P.

    2002-01-01

    The personality profile of 48 youngsters (24 males and 24 females, mean age 8 years, 5 months) with Velo-Cardio-Facial Syndrome (VCFS) was compared with a group of 240 non VCFS control youngsters (matched on age and gender), and, in addition, with groups of youngsters with Prader-Willi (PWS),

  16. The putative imprinted locus D15S9 within the common deletion region for the Prader-Willi and Angelman syndromes encodes two overlapping mRNAs transcribed from opposite strands

    Energy Technology Data Exchange (ETDEWEB)

    Glenn, C.C.; Driscoll, D.J. [Univ. of Florida, Gainesville, FL (United States); Saitoh, S. [Case Western Reserve Univ., Cleveland, OH (United States)] [and others

    1994-09-01

    Prader-Willi syndrome is typically caused by a deletion of paternal 15q11-q13, or maternal uniparental disomy (UPD) of chromosome 15, while Angelman syndrome is caused by a maternal deletion or paternal UPD of the same region. Therefore, these two clinically distinct neurobehavioral syndromes result from differential expression of imprinted genes within 15q11-q13. A 3.1 kb cDNA, DN34, from the D15S9 locus within 15q11-q13 was isolated from a human fetal brain library. We showed previously that DN34 probe detects a DNA methylation imprint and therefore may represent a candidate imprinted gene. Isolation of genomic clones and DNA sequencing demonstrated that the gene segment encoding the partial cDNA DN34 was split by a 2 kb intron, but did not encode a substantial open reading frame (ORF). Preliminary analysis of expression by RT-PCR suggests that this gene is expressed in fetal but not in tested tissue types from the adult, and thus its imprinting status has not been possible to assess at present. Surprisingly, we found an ORF on the antisense strand of the DN34 cDNA. This ORF encodes a putative polypeptide of 505 amino acid residues containing a RING C{sub 3}HC{sub 4} zinc-finger motif and other features of nuclear proteins. Subsequent characterization of this gene, ZNF127, and a mouse homolog, demonstrated expression of 3.2 kb transcript from all tested fetal and adult tissues. Transcripts initiate from within a CpG-island, shown to be differentially methylated on parental alleles in the human. Interestingly, functional imprinting of the mouse homolog was subsequently demonstrated in an F{sub 1} cross by analyzing a VNTR polymorphism in the mRNA. The ZNF127 gene is intronless, has significant overlap with the DN34 gene on the antisense strand, and a 1 kb 3{prime} end within the 2 kb DN34 intron.

  17. Treatment of a Prader-Willi Patient with Recurrent Catatonia

    Directory of Open Access Journals (Sweden)

    Hana M. Poser

    2015-01-01

    Full Text Available Prader-Willi is a genetic disorder characterized by neonatal hypotonia, hyperphagia, short stature, hypogonadism, and mental delay. This disorder can result from multiple mechanisms, most commonly a deletion of paternal chromosome 15, leaving a single maternally derived chromosome 15. Individuals who have a maternal uniparental disomy of chromosome 15 have a higher risk for developing psychosis compared to other forms of Prader-Willi. The following report details the treatment course of a 24-year-old female with Prader-Willi and recurrent catatonia. The patient initially had a positive lorazepam challenge test but subsequently failed treatment with benzodiazepines. She then received eight electroconvulsive therapy (ECT treatments after which she showed improvement from initial catatonic state. However, the resolution in her symptoms did not follow a linear course but would show periods of improvement followed by a return of catatonic features. This case provides an example of the complexity of treatment of a patient with a genetic disorder and recurrent catatonia.

  18. Genes and Disease: Prader-Willi Syndrome

    Science.gov (United States)

    ... MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show details National Center for ... 45K) PDF version of this title (3.8M) Gene sequence Genome view see gene locations Entrez Gene ...

  19. Natural breaking of the maternal silence at the mouse and human imprinted Prader-Willi locus: A whisper with functional consequences.

    Science.gov (United States)

    Matarazzo, Valery; Muscatelli, Françoise

    2013-01-01

    Genomic imprinting is a normal process of epigenetic regulation leading some autosomal genes to be expressed from one parental allele only, the other parental allele being silenced. The reasons why this mechanism has been selected throughout evolution are not clear; however, expression dosage is critical for imprinted genes. There is a paradox between the fact that genomic imprinting is a robust mechanism controlling the expression of specific genes and the fact that this mechanism is based on epigenetic regulation that, per se, should present some flexibility. The robustness has been well studied, revealing the epigenetic modifications at the imprinted locus, but the flexibility has been poorly investigated.   Prader-Willi syndrome is the best-studied disease involving imprinted genes caused by the absence of expression of paternally inherited alleles of genes located in the human 15q11-q13 region. Until now, the silencing of the maternally inherited alleles was like a dogma. Rieusset et al. showed that in absence of the paternal Ndn allele, in Ndn +m/-p mice, the maternal Ndn allele is expressed at an extremely low level with a high degree of non-genetic heterogeneity. In about 50% of these mutant mice, this stochastic expression reduces birth lethality and severity of the breathing deficiency, correlated with a reduction in the loss of serotonergic neurons. Furthermore, using several mouse models, they reveal a competition between non-imprinted Ndn promoters, which results in monoallelic (paternal or maternal) Ndn expression, suggesting that Ndn monoallelic expression occurs in the absence of imprinting regulation. Importantly, specific expression of the maternal NDN allele is also detected in post-mortem brain samples of PWS individuals. Here, similar expression of the Magel2 maternal allele is reported in Magel2 +m/-p mice, suggesting that this loss of imprinting can be extended to other PWS genes. These data reveal an unexpected epigenetic flexibility of PWS

  20. PWS/AS MS-MLPA Confirms Maternal Origin of 15q11.2 Microduplication

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    Angelika J. Dawson

    2015-01-01

    Full Text Available The proximal region of the long arm of chromosome 15q11.2-q13 is associated with various neurodevelopmental disorders, including Prader-Willi (PWS and Angelman (AS syndromes, autism, and other developmental abnormalities resulting from deletions and duplications. In addition, this region encompasses imprinted genes that cause PWS or AS, depending on the parent-of-origin. This imprinting allows for diagnosis of PWS or AS based on methylation status using methylation sensitive (MS multiplex ligation dependent probe amplification (MLPA. Maternally derived microduplications at 15q11.2-q13 have been associated with autism and other neuropsychiatric disorders. Multiple methods have been used to determine the parent-of-origin for 15q11.2-q13 microdeletions and microduplications. In the present study, a four-year-old nondysmorphic female patient with developmental delay was found to have a de novo ~5 Mb duplication within 15q11.2 by oligonucleotide genomic array. In order to determine the significance of this microduplication to the clinical phenotype, the parent-of-origin needed to be identified. The PWS/AS MS-MLPA assay is generally used to distinguish between deletion and uniparental disomy (UPD of 15q11.2-q13, resulting in either PWS or AS. However, our study shows that PWS/AS MS-MLPA can also efficiently distinguish the parental origin of duplications of 15q11.2-q13.

  1. Medication Trials for Hyperphagia and Food-Related Behaviors in Prader–Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Jennifer L. Miller

    2015-06-01

    Full Text Available Prader-Willi syndrome (PWS is a neurodevelopmental disorder caused by the absence of paternally expressed, imprinted genes on chromosome 15q11-13. Individuals with PWS characteristically have poor feeding and lack of appetite in infancy, followed by the development of weight gain and then uncontrolled appetite and lack of satiety, sometime after the age of two. The overwhelming drive to eat is coupled with reduced energy expenditure and decreased caloric requirements, thus, individuals with PWS will become severely obese unless their food intake is strictly controlled. The mechanisms underlying hyperphagia in PWS remain incompletely understood, and to date no drugs have proven effective in controlling appetite. However, clinical trials have started for several medications, which may provide therapeutic options for those with PWS. These medication trials may also provide insight into potential treatments for obesity in the general population. Ideally, these treatments will help alleviate the complex metabolic issues that are part of this syndrome.

  2. The phenotypic spectrum of Schaaf-Yang syndrome : 18 new affected individuals from 14 families

    NARCIS (Netherlands)

    Fountain, Michael D.; Aten, Emmelien; Cho, Megan T.; Juusola, Jane; Walkiewicz, Magdalena A.; Ray, Joseph W.; Xia, Fan; Yang, Yaping; Graham, Brett H.; Bacino, Carlos A.; Potocki, Lorraine; van Haeringen, Arie; Ruivenkamp, Claudia A. L.; Mancias, Pedro; Northrup, Hope; Kukolich, Mary K.; Weiss, Marjan M.; van Ravenswaaij-Arts, Conny M. A.; Mathijssen, Inge B.; Levesque, Sebastien; Meeks, Naomi; Rosenfeld, Jill A.; Lemke, Danielle; Hamosh, Ada; Lewis, Suzanne K.; Race, Simone; Stewart, Laura L.; Hay, Beverly; Lewis, Andrea M.; Guerreiro, Rita L.; Bras, Jose T.; Martins, Marcia P.; Derksen-Lubsen, Gerarda; Peeters, Els; Stumpel, Connie; Stegmann, Sander; Bok, Levinus A.; Santen, Gijs W. E.; Schaaf, Christian P.

    Purpose: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11-13, have recently been reported to cause Schaaf -Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual

  3. Caracterización clínico genética del síndrome Prader Willi

    OpenAIRE

    Travieso Tellez, Anitery; Menéndez García, Reinaldo; Licourt Otero, Deysi

    2014-01-01

    Introducción: el síndrome Prader Willi es un desorden genético causado por la pérdida de genes contenidos en la región 15q11-q13 del cromosoma paterno. Objetivo: describir las características clínicas y genéticas de los pacientes con síndrome Prader Willi. Material y método: se realizó un estudio descriptivo, de corte transversal, con el universo de 15 pacientes con sospecha de síndrome Prader Willi remitidos a consulta provincial de Genética Clínica durante el año 2013. Se consideraron como ...

  4. What Are the Treatments for Prader-Willi Syndrome?

    Science.gov (United States)

    ... These treatments are used to treat small genitals (penis, scrotum, clitoris). Replacement of sex hormones. Replacement of sex hormones during puberty may result in development of adequate secondary sex ...

  5. How Do Health Care Providers Diagnose Prader-Willi Syndrome?

    Science.gov (United States)

    ... OGH) Office of Health Equity (OHE) Office of Legislation and Public Policy (OLPP) Office of Science Policy, ... K., Adam, M. P. (Eds.). Gene reviews . Seattle, WA: University of Washington. Retrieved June 13, 2012, from ...

  6. [Prader-Willi syndrome. Presentation of a case].

    Science.gov (United States)

    Muñoz-Domingo, Elena; Montilla-Pérez, Manuel; Muñoz-Lomas, Fernando; Jiménez Vaquero, César

    2013-01-01

    We report the case of a term infant of 39+1, born by emergency cesarean section due to suspected fetal distress with an Apgar test 4/6/8 and axial hypotonia with weak reflexes. After 52 days of hospitalization an individualized care plan was developed and applied based on Marjory Gordon's functional patterns model and NANDA domains. We used the NANDA diagnoses, interventions according to nursing interventions classification (NIC), and the expected results as classified by nursing outcomes (NOC). Through the care plan, the identified diagnoses and potential complications were resolved. Progress was slow but favorable, stimulating sucking and achieving a good breastfeeding latch, with an appropriate weight gain, decreased muscle stiffness, and increased response to stimuli. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  7. Bloom syndrome and maternal uniparental disomy for chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    Woodage, T.; Prasad, M.; Trent, R.J.; Smith, A. (Children' s Hospital, Camperdown, New South Wales (New Zealand)); Dixon, J.W.; Romain, D.R.; Columbano-Green, L.M.; Selby, R.E. (Wellington Hospital (New Zealand)); Graham, D. (Waikato Hospital, Hamilton (New Zealand)); Rogan, P.K. (Pennsylvania State Univ., Hershey, PA (United States)) (and others)

    1994-07-01

    Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 37 refs., 3 figs., 2 tabs.

  8. Molecular cytogenetic analysis of Inv Dup(15) chromosomes, using probes specific for the Pradar-Willi/Angelman syndrome region: Clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Leana-Cox, J. (Univ. of Maryland School of Medicine, Baltimore, MD (United States)); Jenkins, L. (Kaiser Permanente Medical Group, San Jose, CA (United States)); Palmer, C.G.; Plattner, R. (Indiana School of Medicine, Indianapolis, IN (United States)); Sheppard, L. (Palo Verde Laboratory, Inc., Chandler, AZ (United States)); Flejter, W.L. (Univ. of Michigan, Ann Arbor, MI (United States)); Zackowski, J. (Univ. of Florida Health Science Center, Gainsville, FL (United States)); Tsien, F. (Tulane Univ. School of Medicine, New Orleans, LA (United States)); Schwartz, S. (Case Western Reserve Univ., Cleveland, OH (United States))

    1994-05-01

    Twenty-seven cases of inverted duplications of chromosome 15 (inv dup[15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P<.01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype. 30 refs., 1 fig., 4 tabs.

  9. Caracterización clínico genética del síndrome Prader Willi

    Directory of Open Access Journals (Sweden)

    Anitery Travieso Tellez

    2014-12-01

    Full Text Available Introducción: el síndrome Prader Willi es un desorden genético causado por la pérdida de genes contenidos en la región 15q11-q13 del cromosoma paterno. Objetivo: describir las características clínicas y genéticas de los pacientes con síndrome Prader Willi. Material y método: se realizó un estudio descriptivo, de corte transversal, con el universo de 15 pacientes con sospecha de síndrome Prader Willi remitidos a consulta provincial de Genética Clínica durante el año 2013. Se consideraron como variables clínicas los criterios diagnósticos según Holms, y como variables genéticas los resultados de los estudios cromosómicos y moleculares. Resultados: predominó el sexo femenino en un 66.7%. Las edades estuvieron entre los tres y los 41 años. Los criterios mayores más frecuentes resultaron la obesidad troncular y el retraso del neurodesarrollo en el 100% de los pacientes. Los criterios menores más identificados fueron los disturbios del sueño y las dificultades del lenguaje con un 66.7% cada uno. En ninguno de los casos se detectaron anomalías cromosómicas por cariotipificación. Tres pacientes (60% presentaron la deleción a nivel de la región 15q11-q13 identificada por la técnica de hibridación in sito con fluorescencia. Conclusiones: la definición del diagnóstico en la provincia resulta demorada. Se requiere de reevaluación según los criterios clínicos en las diferentes etapas de la vida para diagnóstico de certeza. La presencia de hipotonía neonatal y dificultades en la alimentación son elementos asociados al diagnóstico por deleción 15q11-q13.

  10. Perfil comportamental e cognitivo de crianças com a síndrome de Prader Willi

    OpenAIRE

    Maria Luiza Guedes de Mesquita

    2008-01-01

    A Síndrome de Prader Willi (SPW) é uma doença genética de origem paterna causada pela perda de expressão de genes no cromossomo 15. Alguns sintomas patognomônicos da doença são a hiperfagia e a obesidade que, na maioria dos casos, ocorre antes dos seis anos e compromete severamente a qualidade vida desses pacientes. O presente estudo se concentrou na área comportamental e teve como objetivos: - identificar a freqüência diária de comportamentos alimentares e ingestão calórica de crianças com S...

  11. Cognitive and behavioral heterogeneity in genetic syndromes

    Directory of Open Access Journals (Sweden)

    Luiz F.L. Pegoraro

    2014-04-01

    Full Text Available OBJECTIVE: this study aimed to investigate the cognitive and behavioral profiles, as well as the psychiatric symptoms and disorders in children with three different genetic syndromes with similar sociocultural and socioeconomic backgrounds. METHODS: thirty-four children aged 6 to 16 years, with Williams-Beuren syndrome (n = 10, Prader-Willi syndrome (n = 11, and Fragile X syndrome (n = 13 from the outpatient clinics of Child Psychiatry and Medical Genetics Department were cognitively assessed through the Wechsler Intelligence Scale for Children (WISC-III. Afterwards, a full-scale intelligence quotient (IQ, verbal IQ, performance IQ, standard subtest scores, as well as frequency of psychiatric symptoms and disorders were compared among the three syndromes. RESULTS: significant differences were found among the syndromes concerning verbal IQ and verbal and performance subtests. Post-hoc analysis demonstrated that vocabulary and comprehension subtest scores were significantly higher in Williams-Beuren syndrome in comparison with Prader-Willi and Fragile X syndromes, and block design and object assembly scores were significantly higher in Prader-Willi syndrome compared with Williams-Beuren and Fragile X syndromes. Additionally, there were significant differences between the syndromes concerning behavioral features and psychiatric symptoms. The Prader-Willi syndrome group presented a higher frequency of hyperphagia and self-injurious behaviors. The Fragile X syndrome group showed a higher frequency of social interaction deficits; such difference nearly reached statistical significance. CONCLUSION: the three genetic syndromes exhibited distinctive cognitive, behavioral, and psychiatric patterns.

  12. Sleep phenotypes in infants and toddlers with neurogenetic syndromes.

    Science.gov (United States)

    Abel, Emily A; Tonnsen, Bridgette L

    2017-10-01

    Although sleep problems are well characterized in preschool- and school-age children with neurogenetic syndromes, little is known regarding the early emergence of these problems in infancy and toddlerhood. To inform syndrome-specific profiles and targets for intervention, we compared parent-reported sleep problems in infants and toddlers with Angelman syndrome (AS), Williams syndrome (WS), and Prader-Willi syndrome (PWS) with patterns observed among same-aged typically developing (TD) controls. Mothers of 80 children (18 AS, 19 WS, 19 PWS, and 24 TD) completed the Brief Infant Sleep Questionnaire. Primary dependent variables included (1) sleep onset latency, (2) total sleep duration, (3) daytime and nighttime sleep duration, and (4) sleep problem severity, as measured by both maternal impression and National Sleep Foundation guidelines. Sleep problems are relatively common in children with neurogenetic syndromes, with 41% of mothers reporting problematic sleep and 29% of children exhibiting abnormal sleep durations as per national guidelines. Across genetic subgroups, problems are most severe in children with AS and WS, particularly in relation to nighttime sleep duration. Although atypical sleep is characteristically reported in each syndrome later in development, infants and toddlers with PWS exhibited largely typical patterns, potentially indicating delayed onset of sleep problems in concordance with other medical features of PWS. Our findings suggest that sleep problems in neurogenetic syndromes emerge as early as infancy and toddlerhood, with variable profiles across genetic subgroups. This work underscores the importance of early sleep screenings as part of routine medical care of neurosyndromic populations and the need for targeted, syndrome-sensitive treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Experimental Functional Analysis of Aggression in Children with Angelman Syndrome

    Science.gov (United States)

    Strachan, Rachel; Shaw, Rebecca; Burrow, Caroline; Horsler, Kate; Allen, Debbie; Oliver, Chris

    2009-01-01

    Background: Kinship theory suggests that genomic imprinting could account for phenotypic behaviors that increase (in the case of Angelman syndrome) or decrease (for Prader-Willi syndrome) the drive to access social resources (adult contact) depending on the imprinting parent-of-origin. Difficult to manage behaviors, such as aggression that is…

  14. Family-based Exercise Intervention for Children and Adolescents with Prader-Willi Syndrome

    Science.gov (United States)

    2012-10-01

    pruebas sensoriales, se les requiere a todos los participantes usar un ames de seguridad para estar protegidos durante las practicas y las primeras pruebas ...cumplir con el programa de aetividad ffsica. Despues del programa todos los materiales y equipos deportivos e interactivos que se le surti6 a su...CALIFORNIA STATE UNIVERSITY, FULLERTON Formulario de Asentimiento Titulo del Proyecto: " Programa Familiar de Ejercicio para Niiios y Adolecentes con

  15. Nutritional and Exercise Aspects of Prader-Willi Syndrome and Childhood Obesity

    Science.gov (United States)

    2013-02-01

    Henderson RC: Bone mineral density and fractures in boys with Duchenne muscular dystrophy . J Pediatr Orthop 2000;20:71-4. 25. Wey HE, Binkley TL, Beare...children with muscular dystrophy presented a lower volume of weight bearing activity 1 and lower BMD in the proximal femur region but not in the spine...Dendale P. (2012). Effect of Acute Endurance and Resistance Exercise on Endocrine Hormones Directly Related to Lipolysis and Skeletal Muscle Protein

  16. What Do Parents Want?: An Analysis of Education-Related Comments Made by Parents of Children with Different Genetic Syndromes.

    Science.gov (United States)

    Fidler, Deborah J.; Lawson, John E.; Hodapp, Robert M.

    2003-01-01

    An analysis of educational desires found parents of children with Down syndrome (n=39) wanted changes in speech therapy and reading services, parents of children with Prader-Willi syndrome (n=25) wanted increases in adaptive physical education services, and parents of children with Williams syndrome (n=26) wanted increases in music services and…

  17. Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for microdeletion syndromes and subtelomere imbalances

    DEFF Research Database (Denmark)

    Kjaergaard, S; Sundberg, K; Jørgensen, F S

    2010-01-01

    The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader-Willi/Angelman, Miller-Dieker, Smith-Magenis, 1p-, Williams), the reciprocal microduplication syndrome...... and imbalance at the subtelomere regions of chromosomes in a routine prenatal setting....

  18. Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for microdeletion syndromes and subtelomere imbalances

    DEFF Research Database (Denmark)

    Kjaergaard, S; Sundberg, K; Jørgensen, F S

    2010-01-01

    The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader-Willi/Angelman, Miller-Dieker, Smith-Magenis, 1p-, Williams), the reciprocal microduplication syndromes...

  19. Cytogenetic and molecular characterization of 57 individuals with the Parder-Willi syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Butler, M.G.; Forrest, K.B.; Miller, L.K. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)

    1994-09-01

    Prader-Willi syndrome (PWS) is characterized by hypotonia, early childhood obesity, mental deficiency, hypogonadism and an interstitial deletion of 15q11q13 of paternal origin in 50-70% of patients. The remaining patients have either submicroscopic deletions, maternal disomy or other anomalies of chromosome 15. We have undertaken cytogenetic and molecular genetic studies of 57 individuals presenting with features consistent with PWS (28 males and 29 females; age range of 3 months to 38 years), 25 with recognizable 15q11q13 deletions (44%), 28 with normal appearing chromosomes (49%), and four patients with other chromosome 15 anomalies (7%). High resolution chromosome analysis and PCR amplification were performed utilizing 17 STRs from 15q11q13 region, quantitative Southern hybridization using seven 15q11q13 probes, and fluorescence in situ hybridization (FISH) using four 15q11q13 probes (4-3R, SNRPN, 3-21, and GABRB3). The cytogenetic deletion was paternal in all PWS families studied but the deletion varied in size in 10 patients. Parental DNA studies from 20 of 28 non-deletion patients showed maternal disomy in 7 patients and biparental inheritance in 13 non-deletion patients. In order to evaluate for submicroscopic deletions, PCR amplification with several loci in the area of the PWS minimal critical region, FISH using SNRPN and quantitative hybridization using a PCR product generated from primers of exons E and H of the SNRPN gene were undertaken on the non-deletion patients. Quantitative hybridization and FISH using SNRPN from 3 of 11 non-deletion patients (excluding maternal disomy cases) showed a submicroscopic deletion. One of these patients also showed a paternal deletion of D15S128 and MN1. We furthur support the use of both cytogenetic and molecular genetic methods for determining the genetic status of PWS patients.

  20. Assistência multiprofissional em unidade de terapia intensiva ao paciente portador de síndrome de Prader-Willi: um enfoque odontológico

    Directory of Open Access Journals (Sweden)

    Juliana Santiago Setti

    2012-03-01

    Full Text Available A síndrome de Prader-Willi (SPW é uma doença neurocomportamental genética que afeta o desenvolvimento da criança, resultando em obesidade, estatura reduzida, hipotonia, distúrbios endócrinos e déficit cognitivo que podem comprometer a integridade da cavidade oral. O presente estudo tem como finalidade apresentar um caso de paciente branco, masculino, 15 anos de idade portador da referida síndrome cujo exame clínico intra-oral evidenciou presença de placa bacteriana, gengivite, má-oclusão, salivação viscosa e múltiplas lesões ulceradas em lábio, mucosa jugal, gengiva inserida, dorso e ventre lingual e lesões papulares ulceradas em borda lateral da língua. Após realização de biópsia excisional, foi constatada a presença de lesão herpética em cavidade oral e lesões cutâneas típicas do herpes que foram associadas a possível causa de encefalite herpética. Assim, observou-se que grande parcela dos efeitos deletérios da SPW podem ser amenizados com o diagnóstico correto e intervenções terapêuticas e educacionais precoces, sendo importante a atuação de uma equipe multiprofissional integrada e o desenvolvimento de protocolos assistenciais para melhor manejo dos pacientes portadores da síndrome de Prader-Willi.

  1. Treino parental para manejo comportamental de crianças com Síndrome de Prader-Willi: impacto sobre a saúde mental e práticas educativas do cuidador

    OpenAIRE

    Mesquita, Maria Luiza Guedes de; Suriano, Raquel; Carreiro, Luiz Renato Rodrigues; Teixeira, Maria Cristina Triguero Veloz

    2016-01-01

    RESUMO Objetivo: verificamos os indicadores de impacto na saúde mental de cuidadores de um programa de treinamento parental para manejo de crianças e adolescentes com Síndrome de Prader-Willi. Métodos: a amostra foi composta por 5 mães de crianças/adolescentes com Síndrome de Prader-Willi entre 6 a 18 anos. Os instrumentos de coleta de dados foram: a) Questionário para verificação de conhecimentos das mães sobre a síndrome, b) Inventário de Auto-avaliação para Adultos de 18 a 59 anos, c) In...

  2. Early diagnosis of Bardet-Biedl syndrome associated with obesity

    Directory of Open Access Journals (Sweden)

    2008-03-01

    Full Text Available One of the urgent problems of modern health care is the increase in the prevalence of obesity among children and adolescents. Late diagnosis and delayed initiation of treatment lead to serious complications such as hypertension, type 2 diabetes mellitus. At present there are quite rare syndromes associated with obesity: Prader-Willi syndrome, Bardet-Biedl, Alström. Bardet-Biedl syndrome, - a disease characterized by obesity central origin, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal dysfunction.

  3. Magel2, a Prader-Willi syndrome candidate gene, modulates the activities of circadian rhythm proteins in cultured cells

    Directory of Open Access Journals (Sweden)

    Devos Julia

    2011-12-01

    Full Text Available Abstract Background The Magel2 gene is most highly expressed in the suprachiasmatic nucleus of the hypothalamus, where its expression cycles in a circadian pattern comparable to that of clock-controlled genes. Mice lacking the Magel2 gene have hypothalamic dysfunction, including circadian defects that include reduced and fragmented total activity, excessive activity during the subjective day, but they have a normal circadian period. Magel2 is a member of the MAGE family of proteins that have various roles in cellular function, but the specific function of Magel2 is unknown. Methods We used a variety of cell-based assays to determine whether Magel2 modifies the properties of core circadian rhythm proteins. Results Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization. Conclusion Consistent with the blunted circadian rhythm observed in Magel2-null mice, these data suggest that Magel2 normally promotes negative feedback regulation of the cellular circadian cycle, through interactions with key core circadian rhythm proteins.

  4. Prader-Willi region non-protein coding RNA 1 suppressed gastric cancer growth as a competing endogenous RNA of microRNA-425-5p.

    Science.gov (United States)

    Chen, Zihao; Ju, Hongping; Yu, Shan; Zhao, Ting; Jing, Xiaojie; Li, Ping; Jia, Jing; Li, Nan; Tan, Bibo; Li, Yong

    2018-03-13

    Gastric cancer (GC) is one of a major global health problem especially in Asia. Nowadays, long non-coding RNA has gained significantly attention in the current research climate such as carcinogenesis. This research desired to explore the mechanism of Prader-Willi region non-protein coding RNA 1 (PWRN1) on regulating GC process. Differentially expressed lncRNAs in GC tissues were screened out through microarray analysis. The RNA and protein expression level was detected by qRT-PCR and western blot. Cell proliferation, apoptosis rate, metastasis abilities were respectively determined by CCK8, flow cytometry, wound healing and transwell assay. The luciferase reporter system was used to verify the targeting relationships between PWRN1, miR-425-5p and PTEN RIP assay was performed to prove whether PWRN1 acted as a competitive endogenous RNA (ceRNA) of miR-425-5p. Tumor xenograft model and immunohistochemistry were developed to study the influence of PWRN1 on tumor growth in vivo Microarray analysis determined that PWRN1 was different expressed between GC tissues and adjacent tissues. QRT-PCR revealed PWRN1 low expression in GC tissues and cells. PWRN1 up-regulated could reduce proliferation and metastasis and increased apoptosis in GC cells, while miR-425-5p had reverse effects. The RIP assay indicated that PWRN1 may target an oncogene miR-425-5p. The tumor xenograft assay found that up-regulated PWRN1 suppressed the tumor growth. The bioinformatic analysis, luciferase assay and western blot indicated that PWRN1 affected PTEN/Akt/MDM2/p53 axis via suppressing miR-425-5p. Our findings suggested that PWRN1 functioned as a ceRNA targeting to miR-425-5p and suppressed GC development via p53 signaling pathway. ©2018 The Author(s).

  5. Cognitive and behavioral heterogeneity in genetic syndromes

    Directory of Open Access Journals (Sweden)

    Luiz F.L. Pegoraro

    2014-03-01

    Full Text Available Objective: this study aimed to investigate the cognitive and behavioral profiles, as well as the psychiatric symptoms and disorders in children with three different genetic syndromes with similar sociocultural and socioeconomic backgrounds. Methods: thirty-four children aged 6 to 16 years, with Williams-Beuren syndrome (n = 10, Prader-Willi syndrome (n = 11, and Fragile X syndrome (n = 13 from the outpatient clinics of Child Psychiatry and Medical Genetics Department were cognitively assessed through the Wechsler Intelligence Scale for Children (WISC-III. Afterwards, a full-scale intelligence quotient (IQ, verbal IQ, performance IQ, standard subtest scores, as well as frequency of psychiatric symptoms and disorders were compared among the three syndromes. Results: significant differences were found among the syndromes concerning verbal IQ and verbal and performance subtests. Post-hoc analysis demonstrated that vocabulary and comprehension subtest scores were significantly higher in Williams-Beuren syndrome in comparison with Prader-Willi and Fragile X syndromes, and block design and object assembly scores were significantly higher in Prader-Willi syndrome compared with Williams-Beuren and Fragile X syndromes. Additionally, there were significant differences between the syndromes concerning behavioral features and psychiatric symptoms. The Prader-Willi syndrome group presented a higher frequency of hyperphagia and self-injurious behaviors. The Fragile X syndrome group showed a higher frequency of social interaction deficits; such difference nearly reached statistical significance. Conclusion: the three genetic syndromes exhibited distinctive cognitive, behavioral, and psychiatric patterns. Resumo: Objetivo: investigar o perfil cognitivo e comportamental, sintomas e transtornos psiquiátricos em crianças com três diferentes síndromes genéticas, com antecedentes socioculturais e socioeconômicos semelhantes. Métodos: trinta e quatro

  6. Treino parental para manejo comportamental de crianças com Síndrome de Prader-Willi: impacto sobre a saúde mental e práticas educativas do cuidador

    Directory of Open Access Journals (Sweden)

    Maria Luiza Guedes de Mesquita

    Full Text Available RESUMO Objetivo: verificamos os indicadores de impacto na saúde mental de cuidadores de um programa de treinamento parental para manejo de crianças e adolescentes com Síndrome de Prader-Willi. Métodos: a amostra foi composta por 5 mães de crianças/adolescentes com Síndrome de Prader-Willi entre 6 a 18 anos. Os instrumentos de coleta de dados foram: a Questionário para verificação de conhecimentos das mães sobre a síndrome, b Inventário de Auto-avaliação para Adultos de 18 a 59 anos, c Inventário de Estilos Parentais/Práticas educativas maternas e paternas; d Levantamento de dificuldades e preocupações sobre os filhos. O estudo foi realizado em quatro fases: pré-intervenção, intervenção, pós-intervenção e seguimento. Resultados: as mães passaram a adotar práticas parentais educativas baseadas na monitoria positiva, diminuíram as práticas de risco. Conclusão: houve melhora em indicadores de dificuldades emocionais das mães, apreenderam a identificar e manejar fatores que prejudicavam a saúde física, o comportamento e a aprendizagem escolar dos filhos e a necessidade do envolvimento de outros familiares no cuidado do filho.

  7. Maternal uniparental disomy for chromosome 14 in a boy with a normal karyotype

    NARCIS (Netherlands)

    Hordijk, R; Scheffer, H; Leegte, B; Hofstra, RMW; Stolte-Dijkstra, [No Value

    1999-01-01

    Groningen, Ne report on a boy with a maternal uniparental disomy for chromosome 14 (UPD(14)). At 7 years of age he was referred to us by the paediatrician because of symptoms of Prader-Willi syndrome (PWS). He showed short stature, obesity, mild developmental delay, cryptorchidism, and some mild

  8. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    DEFF Research Database (Denmark)

    Isles, Anthony R; Ingason, Andrés; Lowther, Chelsea

    2016-01-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications m...

  9. The inv dup (15 or idic (15 syndrome (Tetrasomy 15q

    Directory of Open Access Journals (Sweden)

    Battaglia Agatino

    2008-11-01

    Full Text Available Abstract The inv dup(15 or idic(15 syndrome displays distinctive clinical findings represented by early central hypotonia, developmental delay and intellectual disability, epilepsy, and autistic behaviour. Incidence at birth is estimated at 1 in 30,000 with a sex ratio of almost 1:1. Developmental delay and intellectual disability affect all individuals with inv dup(15 and are usually moderate to profound. Expressive language is absent or very poor and often echolalic. Comprehension is very limited and contextual. Intention to communicate is absent or very limited. The distinct behavioral disorder shown by children and adolescents has been widely described as autistic or autistic-like. Epilepsy with a wide variety of seizure types can occur in these individuals, with onset between 6 months and 9 years. Various EEG abnormalities have been described. Muscle hypotonia is observed in almost all individuals, associated, in most of them, with joint hyperextensibility and drooling. Facial dysmorphic features are absent or subtle, and major malformations are rare. Feeding difficulties are reported in the newborn period. Chromosome region 15q11q13, known for its instability, is highly susceptible to clinically relevant genomic rearrangements, such as supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15 results in tetrasomy 15p and partial tetrasomy 15q. The large rearrangements, containing the Prader-Willi/Angelman syndrome critical region (PWS/ASCR, are responsible for the inv dup(15 or idic(15 syndrome. Diagnosis is achieved by standard cytogenetics and FISH analysis, using probes both from proximal chromosome 15 and from the PWS/ASCR. Microsatellite analysis on parental DNA or methylation analysis on the proband DNA, are also needed to detect the parent-of-origin of the inv dup(15 chromosome. Array CGH has been shown to provide a powerful approach for identifying and detecting the extent of the

  10. Public Water Supply Systems (PWS)

    Data.gov (United States)

    Kansas Data Access and Support Center — This dataset includes boundaries for most public water supply systems (PWS) in Kansas (525 municipalities, 289 rural water districts and 13 public wholesale water...

  11. 3D Architecture, dynamics as well as functional implications of genome organization of the Prader-Willi/Angelmann syndrome region & the Immunoglobin Heavy-Chain locus

    NARCIS (Netherlands)

    T.A. Knoch (Tobias)

    2008-01-01

    textabstractThe general 3D architecture of the immunoglobin heavy-chain (Igh) locus was determined by a novel interdisciplinary combination of high-resolution FISH and high-resolution epifluorescence spectral distance microscopy with analytical analysis, computer simulations, as well as

  12. Examining the Relationship between Heart Rate and Problem Behavior: A Case Study of Severe Skin Picking in Prader-Willi Syndrome

    Science.gov (United States)

    Hall, Scott S.; Hammond, Jennifer L.; Hustyi, Kristin M.

    2013-01-01

    Few studies have examined the relationship between heart rate and self-injurious behavior (SIB) shown by individuals with IDD (intellectual and developmental disabilities). In this single-case study, we simultaneously monitored heart rate and activity levels during a functional analysis of severe skin picking behavior exhibited by a young man with…

  13. MOMO Syndrome with Holoprosencephaly and Cryptorchidism: Expanding the Spectrum of the New Obesity Syndrome

    Directory of Open Access Journals (Sweden)

    Sheetal Sharda

    2011-01-01

    Full Text Available There are multiple genetic disorders with known or unknown etiology grouped under obesity syndromes. Inspite of having multisystem involvement and often having a characteristic presentation, the understanding of the genetic causes in the majority of these syndromes is still lacking. The common obesity syndromes are Bardet-Biedl, Prader-Willi, Alstrom, Albright's hereditary osteodystrophy, Carpenter, Rubinstein-Taybi, Fragile X, and Börjeson-Forssman-Lehman syndrome. The list is ever increasing as new syndromes are being added to it. One of the recent additions is MOMO syndrome, with about five such cases being reported in literature. Expanding the spectrum of clinical features, we report the first case of MOMO syndrome from India with lobar variant of holoprosencephaly and cryptorchidism, which have not been reported previously.

  14. Imprinted Expression of SNRPN in Human Preimplantation Embryos

    OpenAIRE

    Huntriss, John; Daniels, Robert; Bolton, Virginia; Monk, Marilyn

    1998-01-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurogenetic disorders arising from a loss of expression of imprinted genes within the human chromosome region 15q11-q13. Recent evidence suggests that the SNRPN gene, which is defective in PWS, plays a central role in the imprinting-center regulation of the PWS/AS region. To increase our understanding of the regulation of expression of this imprinted gene, we have developed single-cell-sensitive procedures for...

  15. Three patients with Schaaf-Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities.

    Science.gov (United States)

    Enya, Takuji; Okamoto, Nobuhiko; Iba, Yoshinori; Miyazawa, Tomoki; Okada, Mitsuru; Ida, Shinobu; Naruto, Takuya; Imoto, Issei; Fujita, Atsushi; Miyake, Noriko; Matsumoto, Naomichi; Sugimoto, Keisuke; Takemura, Tsukasa

    2018-03-01

    MAGEL2 is the paternally expressed gene within Prader-Willi syndrome critical region at 15q11.2. We encountered three individuals in whom truncating mutations of MAGEL2 were identified. Patients 1 and 2, siblings born to healthy, non-consanguineous Japanese parents, showed generalized hypotonia, lethargy, severe respiratory difficulty, poor feeding, and multiple anomalies including arthrogryposis soon after birth. We carried out whole-exome sequencing, which detected a MAGEL2 mutation (c.1912C>T, p.Gln638*, heterozygous). The patients' father was heterozygous for the mutation. Patient 3 was a female infant, showed respiratory difficulty reflecting pulmonary hypoplasia, generalized hypotonia, feeding difficulty and multiple anomalies soon after birth. Targeted next-generation sequencing detected a novel heterozygous mutation in MAGEL2 (c.3131C>A, p.Ser1044*). This mutation was not found in the parents. MAGEL2 mutations, first reported to be the cause of the Prader-Willi like syndrome with autism by Schaaf et al. (2013) Nature Genetics, 45: 1405-1408 show the wide range of phenotypic spectrum from lethal arthrogryposis multiplex congenital to autism spectrum disorder (ASD) and mild intellectual disability (ID). Our results indicate that MAGEL2 mutations cause multiple congenital anomalies and intellectual disability accompanied by arthrogryposis multiplex congenita and various endocrinologic abnormalities, supporting that the view that clinical phenotypes of MAGEL2 mutations are variable. © 2018 Wiley Periodicals, Inc.

  16. NCBI nr-aa BLAST: CBRC-SARA-01-1746 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-SARA-01-1746 ref|NP_653200.2| non-imprinted in Prader-Willi/Angelman syndrome ...1 [Homo sapiens] sp|Q7RTP0|NIPA1_HUMAN Non-imprinted in Prader-Willi/Angelman syndrome region protein 1 tpg|...DAA01477.1| TPA_exp: non-imprinted in Prader-Willi/Angelman syndrome 1 [Homo sapiens] NP_653200.2 1e-113 81% ...

  17. NCBI nr-aa BLAST: CBRC-AGAM-04-0111 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-AGAM-04-0111 ref|NP_001029470.1| non imprinted in Prader-Willi/Angelman syndro...me 2 [Bos taurus] sp|Q3SWX0|NIPA2_BOVIN Non-imprinted in Prader-Willi/Angelman syndrome region protein 2 hom...olog gb|AAI04628.1| Non imprinted in Prader-Willi/Angelman syndrome 2 [Bos taurus] NP_001029470.1 2e-72 51% ...

  18. NCBI nr-aa BLAST: CBRC-SARA-01-1746 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available 1| unnamed protein product [Mus musculus] gb|EAW65549.1| non imprinted in Prader-Willi/Angelman syndrome 1, ...isoform CRA_a [Homo sapiens] gb|EAW65551.1| non imprinted in Prader-Willi/Angelman syndrome 1, isoform CRA_a... [Homo sapiens] gb|ABM82178.1| non imprinted in Prader-Willi/Angelman syndrome 1 ...[synthetic construct] gb|ABM85364.1| non imprinted in Prader-Willi/Angelman syndrome 1 [synthetic construct] CAD97953.1 1e-113 81% ...

  19. NCBI nr-aa BLAST: CBRC-STRI-01-2632 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2632 ref|NP_001100988.1| non imprinted in Prader-Willi/Angelman syndro...me 2 homolog [Rattus norvegicus] gb|EDL86457.1| non imprinted in Prader-Willi/Angelman syndrome 2 homolog (h...uman) (predicted), isoform CRA_a [Rattus norvegicus] gb|EDL86458.1| non imprinted in Prader-Willi/Angelman s

  20. Análise comparativa entre as metodologias de PCR metilação-específica (MSP, Southern blot (SB e FISH utilizadas no diagnóstico genético molecular de pacientes com suspeita clínica das síndromes de Prader-Willi ou Angelman

    Directory of Open Access Journals (Sweden)

    Bruna Oliveira

    2016-08-01

    Full Text Available Introdução: Prader-Willi (SPW e Angelman (SA são síndromes clinicamente distintas, causadas pela perda de expressão de genes na região cromossômica 15q11.2-q13, de origem paterna ou materna, respectivamente. Ambas compartilham os mesmos métodos diagnósticos. Nossos objetivos foram: a analisar por PCR metilação-específica (MSP pacientes com suspeita clínica de SPW/SA; b comparar resultados de diferentes metodologias de diagnóstico molecular; c aplicar a técnica MSP na rotina assistencial de pacientes encaminhados ao Serviço de Genética Médica/Hospital de Clínicas de Porto Alegre (SGM/HCPA. Métodos: Foram analisados 123 pacientes com suspeita clínica de SPW (n = 71 ou SA (n = 52 por MSP. Desses, 79 possuíam análise prévia por hibridação in situ fluorescente (FISH e/ou Southern blot (SB. Resultados: Foram detectados 21 casos positivos – 15 de SPW (12,19% e 6 de SA (4,88%. Nove pacientes tiveram etiologia molecular determinada, sendo sete com diagnóstico de SPW (quatro dissomias uniparentais – UPD15 materna – e três deleções na região 15q11-13 e dois com diagnóstico de SA (um com UPD15 paterna e um com deleção na região 15q11-13. Foram observados resultados equivalentes entre MSP e SB e resultados discrepantes entre MSP e FISH (n = 4. Foram padronizados dois protocolos de MSP para confirmação dos resultados e controle interno de qualidade. Conclusão: O perfil de detecção de cada técnica varia de acordo com o mecanismo etiológico presente. A análise por MSP detecta alterações no padrão de metilação geradas por deleção, UPD e defeitos de imprinting, sem identificar o mecanismo etiológico responsável. Contudo, mostrou ser eficiente para confirmação do diagnóstico clínico e screening dos pacientes com suspeita clínica sugestiva de SPW e SA. Diante de resultados positivos, é importante a identificação do mecanismo molecular subjacente para correlação genótipo-fenótipo e determina

  1. Early childhood obesity is associated with compromised cerebellar development.

    Science.gov (United States)

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

  2. NCBI nr-aa BLAST: CBRC-SARA-01-1746 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-SARA-01-1746 ref|NP_001100989.1| non imprinted in Prader-Willi/Angelman syndro...me 1 homolog [Rattus norvegicus] gb|EDL86455.1| non imprinted in Prader-Willi/Angelman syndrome 1 homolog (human) (predicted) [Rattus norvegicus] NP_001100989.1 1e-113 80% ...

  3. Syndrome identification based on 2D analysis software.

    Science.gov (United States)

    Boehringer, Stefan; Vollmar, Tobias; Tasse, Christiane; Wurtz, Rolf P; Gillessen-Kaesbach, Gabriele; Horsthemke, Bernhard; Wieczorek, Dagmar

    2006-10-01

    Clinical evaluation of children with developmental delay continues to present a challenge to the clinicians. In many cases, the face provides important information to diagnose a condition. However, database support with respect to facial traits is limited at present. Computer-based analyses of 2D and 3D representations of faces have been developed, but it is unclear how well a larger number of conditions can be handled by such systems. We have therefore analysed 2D pictures of patients each being affected with one of 10 syndromes (fragile X syndrome; Cornelia de Lange syndrome; Williams-Beuren syndrome; Prader-Willi syndrome; Mucopolysaccharidosis type III; Cri-du-chat syndrome; Smith-Lemli-Opitz syndrome; Sotos syndrome; Microdeletion 22q11.2; Noonan syndrome). We can show that a classification accuracy of >75% can be achieved for a computer-based diagnosis among the 10 syndromes, which is about the same accuracy achieved for five syndromes in a previous study. Pairwise discrimination of syndromes ranges from 80 to 99%. Furthermore, we can demonstrate that the criteria used by the computer decisions match clinical observations in many cases. These findings indicate that computer-based picture analysis might be a helpful addition to existing database systems, which are meant to assist in syndrome diagnosis, especially as data acquisition is straightforward and involves off-the-shelf digital camera equipment.

  4. NCBI nr-aa BLAST: CBRC-SARA-01-1746 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-SARA-01-1746 ref|NP_705806.1| non-imprinted in Prader-Willi/Angelman syndrome ...1 [Mus musculus] sp|Q8BHK1|NIPA1_MOUSE Non-imprinted in Prader-Willi/Angelman syndrome region protein 1 homo...protein product [Mus musculus] gb|AAH55828.1| Non imprinted in Prader-Willi/Angel...man syndrome 1 homolog (human) [Mus musculus] gb|EDL21870.1| non imprinted in Prader-Willi/Angelman syndrome 1 homolog (human) [Mus musculus] NP_705806.1 1e-113 81% ... ...log gb|AAM34534.1| non-imprinted in Prader-Willi/Angelman syndrome 1 [Mus musculus] dbj|BAC32809.1| unnamed

  5. NCBI nr-aa BLAST: CBRC-HSAP-15-0013 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-15-0013 ref|NP_001008860.1| non imprinted in Prader-Willi/Angelman syndro...me 2 isoform a [Homo sapiens] ref|NP_112184.4| non imprinted in Prader-Willi/Angelman syndrome 2 isoform a [...Homo sapiens] ref|NP_001008892.1| non imprinted in Prader-Willi/Angelman syndrome 2 isoform a [Homo sapiens]... sp|Q8N8Q9|NIPA2_HUMAN Non-imprinted in Prader-Willi/Angelman syndrome region pro...tein 2 sp|Q5R7Q3|NIPA2_PONPY Non-imprinted in Prader-Willi/Angelman syndrome region protein 2 homolog dbj|BA

  6. Familial cryptic translocation in Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Weyerts, L.K.; Wiley, J.E.; Loud, K.M. [ECU School of Medicine, Greenville, NC (United States)] [and others

    1994-09-01

    The majority of patients with Angelman syndrome have been shown to have a cytogenetic or molecular deletion on the maternally derived chromosome 15. We report on a case of Angelman syndrome in which this deletion occurs as an unbalanced cryptic translocation involving chromosomes 14 and 15. The proband was diagnosed clinically as having Angelman syndrome. Multiple cytogenetic studies were done without detecting any deletion. When DNA probes (Oncor) specific for the Prader Willi/Angelman locus became available, the patient was restudied and found to be deleted for {open_quotes}region A{close_quotes} (D15S11) but not for {open_quotes}region B{close_quotes} (GABRB3). No other abnormality was detected. The proband`s mother was then studied. The chromosome 15 marker probe and D15S11 were detected on different chromosomes. Using alpha-satellite probes, a cryptic 14;15 translocation was uncovered. This balanced translocation was also found to be carried by the sister of the proband. This case, along with a case presented at the 1993 ASHG meeting, illustrates the need for using acrocentric probes when studying Angelman syndrome patients. The proband was studied using additional probes specific for this region and found to be deleted for SNRPN but not for D15S10. The breakpoint of the translocation in this patient delineates the smallest deletion of the Angelman syndrome region reported to date and therefore may represent the specific gene involved.

  7. Water Service Areas - Public Water Supplier's (PWS) Service Areas

    Data.gov (United States)

    NSGIC Education | GIS Inventory — Boundaries of current public water supplier's (PWS) service areas. This data set contains the present service area boundary of the water system and does not contain...

  8. Behavioral phenotypes of genetic syndromes with intellectual disability: comparison of adaptive profiles.

    Science.gov (United States)

    Di Nuovo, Santo; Buono, Serafino

    2011-10-30

    The study of distinctive and consistent behaviors in the most common genetic syndromes with intellectual disability is useful to explain abnormalities or associated psychiatric disorders. The behavioral phenotypes revealed outcomes totally or partially specific for each syndrome. The aim of our study was to compare similarities and differences in the adaptive profiles of the five most frequent genetic syndromes, i.e. Down syndrome, Williams syndrome, Angelman syndrome, Prader-Willi syndrome, and Fragile-X syndrome (fully mutated), taking into account the relation with chronological age and the overall IQ level. The research was carried out using the Vineland Adaptive Behavior Scale (beside the Wechsler Intelligence scales to obtain IQ) with a sample of 181 persons (107 males and 74 females) showing genetic syndromes and mental retardation. Syndrome-based groups were matched for chronological age and mental age (excluding the Angelman group, presenting with severe mental retardation). Similarities and differences in the adaptive profiles are described, relating them to IQs and maladaptive behaviors. The results might be useful in obtaining a global index of adjustment for the assessment of intellectual disability level as well as for educational guidance and rehabilitative plans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. [Monogenic and syndromic symptoms of morbid obesity. Rare but important].

    Science.gov (United States)

    Wiegand, S; Krude, H

    2015-02-01

    Monogenic and syndromic obesity are rare diseases with variable manifestation. Therefore diagnosis is difficult and often delayed. The purpose of this work was to develop a clinical diagnostic algorithm for earlier diagnosis. Available publications for clinical symptoms and molecular defects of monogenic and syndromic obesity cases were evaluated. Monogenic and syndromic obesity can be expected in cases with early manifestation before the age of 5 years and a BMI above 40 or above the 99th percentile. Syndromic cases are mostly associated with a low IQ and dwarfism. Monogenic cases are associated with additional endocrine defects. Measurement of serum leptin proves the treatable leptin deficiency. Sequencing of the melanocortin-4 receptor gene (MC4R) allows diagnosis of the most frequent monogenic form of obesity. Treatment with a melanocyte-stimulating hormone (MSH) analog can be expected in the future. Early treatment of children with Prader-Willi syndrome can prevent severe obesity. Because in some cases treatment is available, monogenic and syndromic obesity should be diagnosed early. Based on the disease symptoms, serum leptin, and MC4R sequencing, a diagnostic algorithm is proposed, which can be used to diagnose cases of morbid obesity.

  10. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

    Science.gov (United States)

    Dichter, Gabriel S; Damiano, Cara A; Allen, John A

    2012-07-06

    This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

  11. NCBI nr-aa BLAST: CBRC-STRI-01-2632 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2632 ref|NP_001029470.1| non imprinted in Prader-Willi/Angelman syndro...me 2 [Bos taurus] sp|Q3SWX0|NIPA2_BOVIN RecName: Full=Magnesium transporter NIPA2; AltName: Full=Non-imprint...ed in Prader-Willi/Angelman syndrome region protein 2 homolog gb|AAI04628.1| Non imprinted in Prader-Willi/Angelman syndrome 2 [Bos taurus] NP_001029470.1 1e-140 88% ...

  12. Classifying dysmorphic syndromes by using artificial neural network based hierarchical decision tree.

    Science.gov (United States)

    Özdemir, Merve Erkınay; Telatar, Ziya; Eroğul, Osman; Tunca, Yusuf

    2018-05-01

    Dysmorphic syndromes have different facial malformations. These malformations are significant to an early diagnosis of dysmorphic syndromes and contain distinctive information for face recognition. In this study we define the certain features of each syndrome by considering facial malformations and classify Fragile X, Hurler, Prader Willi, Down, Wolf Hirschhorn syndromes and healthy groups automatically. The reference points are marked on the face images and ratios between the points' distances are taken into consideration as features. We suggest a neural network based hierarchical decision tree structure in order to classify the syndrome types. We also implement k-nearest neighbor (k-NN) and artificial neural network (ANN) classifiers to compare classification accuracy with our hierarchical decision tree. The classification accuracy is 50, 73 and 86.7% with k-NN, ANN and hierarchical decision tree methods, respectively. Then, the same images are shown to a clinical expert who achieve a recognition rate of 46.7%. We develop an efficient system to recognize different syndrome types automatically in a simple, non-invasive imaging data, which is independent from the patient's age, sex and race at high accuracy. The promising results indicate that our method can be used for pre-diagnosis of the dysmorphic syndromes by clinical experts.

  13. Hypothalamic dysfunction

    Science.gov (United States)

    ... apoplexy , subarachnoid hemorrhage Genetic disorders, such as Prader-Willi syndrome , familial diabetes insipidus , Kallmann syndrome Infections and ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

  14. Testicular failure

    Science.gov (United States)

    ... Genetic diseases, such as Klinefelter syndrome or Prader-Willi syndrome Other diseases, such as cystic fibrosis The ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

  15. Hypotonia

    Science.gov (United States)

    ... damage include: Down syndrome Spinal muscular atrophy Prader-Willi syndrome Tay-Sachs disease Trisomy 13 Other disorders ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

  16. NCBI nr-aa BLAST: CBRC-PABE-16-0005 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PABE-16-0005 ref|XP_001106072.1| PREDICTED: similar to non imprinted in Prader...-Willi/Angelman syndrome 2 isoform a isoform 2 [Macaca mulatta] ref|XP_001106137.1| PREDICTED: similar to non imprint...oform 4 [Macaca mulatta] ref|XP_001106265.1| PREDICTED: similar to non imprinted in Prader-Willi/Angelman syndrome 2 isoform a isoform 5 [Macaca mulatta] XP_001106072.1 1e-114 79% ... ...DICTED: similar to non imprinted in Prader-Willi/Angelman syndrome 2 isoform a is...ed in Prader-Willi/Angelman syndrome 2 isoform a isoform 3 [Macaca mulatta] ref|XP_001106204.1| PRE

  17. NCBI nr-aa BLAST: CBRC-STRI-01-2632 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2632 ref|XP_001106072.1| PREDICTED: similar to non imprinted in Prader...-Willi/Angelman syndrome 2 isoform a isoform 2 [Macaca mulatta] ref|XP_001106137.1| PREDICTED: similar to non imprint...oform 4 [Macaca mulatta] ref|XP_001106265.1| PREDICTED: similar to non imprinted in Prader-Willi/Angelman syndrome 2 isoform a isoform 5 [Macaca mulatta] XP_001106072.1 1e-142 88% ... ...DICTED: similar to non imprinted in Prader-Willi/Angelman syndrome 2 isoform a is...ed in Prader-Willi/Angelman syndrome 2 isoform a isoform 3 [Macaca mulatta] ref|XP_001106204.1| PRE

  18. NCBI nr-aa BLAST: CBRC-HSAP-15-0013 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-15-0013 ref|XP_001106072.1| PREDICTED: similar to non imprinted in Prader...-Willi/Angelman syndrome 2 isoform a isoform 2 [Macaca mulatta] ref|XP_001106137.1| PREDICTED: similar to non imprint...oform 4 [Macaca mulatta] ref|XP_001106265.1| PREDICTED: similar to non imprinted in Prader-Willi/Angelman syndrome 2 isoform a isoform 5 [Macaca mulatta] XP_001106072.1 1e-115 79% ... ...DICTED: similar to non imprinted in Prader-Willi/Angelman syndrome 2 isoform a is...ed in Prader-Willi/Angelman syndrome 2 isoform a isoform 3 [Macaca mulatta] ref|XP_001106204.1| PRE

  19. NCBI nr-aa BLAST: CBRC-STRI-01-2632 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2632 ref|NP_001008860.1| non imprinted in Prader-Willi/Angelman syndro...me 2 isoform a [Homo sapiens] ref|NP_112184.4| non imprinted in Prader-Willi/Angelman syndrome 2 isoform a [...Homo sapiens] ref|NP_001008892.1| non imprinted in Prader-Willi/Angelman syndrome 2 isoform a [Homo sapiens]... ref|NP_001126291.1| non imprinted in Prader-Willi/Angelman syndrome 2 [Pongo abe...lii] sp|Q8N8Q9|NIPA2_HUMAN RecName: Full=Magnesium transporter NIPA2; AltName: Full=Non-imprinted in Prader-

  20. Challenging behavior: Behavioral phenotypes of some genetic syndromes

    Directory of Open Access Journals (Sweden)

    Buha Nataša

    2014-01-01

    Full Text Available Challenging behavior in individuals with mental retardation (MR is relatively frequent, and represents a significant obstacle to adaptive skills. The frequency of specific forms and manifestations of challenging behavior can depend on a variety of personal and environmental factors. There are several prominent theoretical models regarding the etiology of challenging behavior and psychopathology in persons with MR: behavioral, developmental, socio-cultural and biological. The biological model emphasizes the physiological, biochemical and genetic factors as the potential source of challenging behavior. The progress in the field of genetics and neuroscience has opened the opportunity to study and discover the neurobiological basis of phenotypic characteristics. Genetic syndromes associated with MR can be followed by a specific set of problems and disorders which constitutes their behavioral phenotype. The aim of this paper was to present challenging behaviors that manifest in the most frequently studied syndromes: Down syndrome, Fragile X syndrome, Williams syndrome, Prader-Willi syndrome and Angelman syndrome. The concept of behavioral phenotype implies a higher probability of manifesting specific developmental characteristics and specific behaviors in individuals with a certain genetic syndrome. Although the specific set of (possible problems and disorders is distinctive for the described genetic syndromes, the connection between genetics and behavior should be viewed through probabilistic dimension. The probabilistic concept takes into consideration the possibility of intra-syndrome variability in the occurrence, intensity and time onset of behavioral characteristics, at which the higher variability the lower is the specificity of the genetic syndrome. Identifying the specific pattern of behavior can be most important for the process of early diagnosis and prognosis. In addition, having knowledge about behavioral phenotype can be a landmark in

  1. A Case of Fundus Oculi Albinoticus Diagnosed as Angelman Syndrome by Genetic Testing

    Directory of Open Access Journals (Sweden)

    Yurie Fukiyama

    2018-02-01

    Full Text Available Purpose: To report a case of fundus oculi albinoticus diagnosed as Angelman syndrome (AS via genetic testing. Case Report: This study reports on a 4-year-old boy. Since he had been having respiratory disturbance since birth, he underwent a complete physical examination to investigate the cause. The results indicated that he had various brain congenital abnormalities, such as a thin corpus callosum, as well as hydronephrosis, an atrial septal defect, and skin similar to patients with fundus oculi albinoticus. Examination revealed bilateral fundus oculi albinoticus, mild iridic hypopigmentation, optic atrophy, and poor visual tracking. Genetic testing revealed a deletion in the Prader-Willi syndrome/AS region on chromosome 15, and together with the results of methylation analysis, his condition was diagnosed as AS. Follow-up examinations revealed no change in the fundus oculi albinoticus and optic atrophy, nor did they indicate poor visual tracking. Conclusions: When fundus oculi albinoticus and optic atrophy are observed in patients with multiple malformations, AS should be considered as a differential diagnosis.

  2. Angelman syndrome associated with an inversion of chromosome 15q11.2q24.3

    Energy Technology Data Exchange (ETDEWEB)

    Greger, V.; Knoll, J.H.M.; Wagstaff, J.; Lalande, M. [and others

    1997-03-01

    Angelman syndrome (AS) most frequently results from large ({ge}5 Mb) de novo deletions of chromosome 15q11-q13. The deletions are exclusively of maternal origin, and a few cases of paternal uniparental disomy of chromosome 15 have been reported. The latter finding indicates that AS is caused by the absence of a maternal contribution to the imprinted 15q11-q13 region. Failure to inherit a paternal 15q11-q13 contribution results in the clinically distinct disorder of Prader-Willi syndrome. Cases of AS resulting from translocations or pericentric inversions have been observed to be associated with deletions, and there have been no confirmed reports of balanced rearrangements in AS. We report the first such case involving a paracentric inversion with a breakpoint located {approximately}25 kb proximal to the reference marker D15S10. This inversion has been inherited from a phenotypically normal mother. No deletion is evident by molecular analysis in this case, by use of cloned fragments mapped to within {approximately}1 kb of the inversion breakpoint. Several hypotheses are discussed to explain the relationship between the inversion and the AS phenotype. 47 refs., 3 figs.

  3. Dietary management and genetic predisposition

    DEFF Research Database (Denmark)

    Jensen, Hanne Holbæk; Larsen, Lesli Hingstrup

    2013-01-01

    variation, and epigenetics might identify additional genetic contributions to obesity, and the use of omics data with integration of nutrigenetics and nutrigenomics will identify genetic subgroups who will benefit from specific dietary advice to optimize health and prevent disease. Keywords: Diet . Mutation...... epidemically worldwide, the investigation of genetic predisposition might help to prevent and treat obesity. Predisposition to obesity includes syndromes, such as Prader-Willi Syndrome (PWS), severe early-onset obesity, such as mutations in the melanocortin 4 receptor (MC4R), and common forms of obesity......, such as genetic variation in the fat mass and obesity associated gene (FTO). Several studies have explored gene-diet interactions in obesity, weight loss, and regain, but there is a lack of consistency in the identified interactions. This inconsistency is most probably due to a low-moderate effect size...

  4. Genomic Imprinting Is Implicated in the Psychology of Music.

    Science.gov (United States)

    Mehr, Samuel A; Kotler, Jennifer; Howard, Rhea M; Haig, David; Krasnow, Max M

    2017-10-01

    Why do people sing to babies? Human infants are relatively altricial and need their parents' attention to survive. Infant-directed song may constitute a signal of that attention. In Prader-Willi syndrome (PWS), a rare disorder of genomic imprinting, genes from chromosome 15q11-q13 that are typically paternally expressed are unexpressed, which results in exaggeration of traits that reduce offspring's investment demands on the mother. PWS may thus be associated with a distinctive musical phenotype. We report unusual responses to music in people with PWS. Subjects with PWS ( N = 39) moved more during music listening, exhibited greater reductions in heart rate in response to music listening, and displayed a specific deficit in pitch-discrimination ability relative to typically developing adults and children ( N = 589). Paternally expressed genes from 15q11-q13, which are unexpressed in PWS, may thus increase demands for music and enhance perceptual sensitivity to music. These results implicate genomic imprinting in the psychology of music, informing theories of music's evolutionary history.

  5. Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

    OpenAIRE

    Lukoshe, Akvile; White, Tonya; Schmidt, Marcus N; van der Lugt, Aad; Hokken-Koelega, Anita C

    2013-01-01

    Background Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical foc...

  6. Deletion 22q13.3 syndrome

    Directory of Open Access Journals (Sweden)

    Phelan Mary C

    2008-05-01

    Full Text Available Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH or array comparative genomic hybridization (CGH is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy. Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements

  7. Albinism and Developmental Delay: The Need to Test for 15q11–q13 deletion

    Science.gov (United States)

    Saadeh, Reem; Lisi, Emily C.; Batista, Denise A.S.; McIntosh, Iain; Hoover-Fong, Julie E.

    2007-01-01

    We report a 17-month-old African female with cutaneous and ophthalmologic features of oculocutaneous albinism type 2 as well as microcephaly, absent speech, tremulous movements. P gene mutations within the Angelman/Prader-Willi syndrome critical region at 15q11–q13 cause oculocutaneous albinism type 2. Co-morbid oculocutaneous albinism and Angelman syndrome were suspected and confirmed by cytogenetics. Phenotypic features of Angelman syndrome or Prader-Willi syndrome in a patient with albinism should prompt further investigation. PMID:17903679

  8. NCBI nr-aa BLAST: CBRC-STRI-01-2632 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2632 ref|NP_076136.2| non-imprinted in Prader-Willi/Angelman syndrome ...2 [Mus musculus] sp|Q9JJC8|NIPA2_MOUSE RecName: Full=Magnesium transporter NIPA2; AltName: Full=Non-imprinte...tein product [Mus musculus] tpg|DAA01178.1| TPA_exp: non-imprinted in Prader-Willi/Angelman syndrome 2 [Mus ...musculus] dbj|BAE32806.1| unnamed protein product [Mus musculus] gb|EDL21872.1| non imprint...ed in Prader-Willi/Angelman syndrome 2 homolog (human), isoform CRA_a [Mus musculus] gb|EDL21874.1| non imprint

  9. Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation.

    Directory of Open Access Journals (Sweden)

    Boris V Skryabin

    2007-12-01

    Full Text Available Prader-Willi syndrome (PWS [MIM 176270] is a neurogenetic disorder characterized by decreased fetal activity, muscular hypotonia, failure to thrive, short stature, obesity, mental retardation, and hypogonadotropic hypogonadism. It is caused by the loss of function of one or more imprinted, paternally expressed genes on the proximal long arm of chromosome 15. Several potential PWS mouse models involving the orthologous region on chromosome 7C exist. Based on the analysis of deletions in the mouse and gene expression in PWS patients with chromosomal translocations, a critical region (PWScr for neonatal lethality, failure to thrive, and growth retardation was narrowed to the locus containing a cluster of neuronally expressed MBII-85 small nucleolar RNA (snoRNA genes. Here, we report the deletion of PWScr. Mice carrying the maternally inherited allele (PWScr(m-/p+ are indistinguishable from wild-type littermates. All those with the paternally inherited allele (PWScr(m+/p- consistently display postnatal growth retardation, with about 15% postnatal lethality in C57BL/6, but not FVB/N crosses. This is the first example in a multicellular organism of genetic deletion of a C/D box snoRNA gene resulting in a pronounced phenotype.

  10. Neonatal maternal deprivation response and developmental changes in gene expression revealed by hypothalamic gene expression profiling in mice.

    Directory of Open Access Journals (Sweden)

    Feng Ding

    Full Text Available Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS. Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period.

  11. The imprinted SNRPN gene is associated with a polycistronic mRNA and an imprinting control element

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, S.; Nicholls, R.D. [Case Western Reserve Univ., Cleveland, OH (United States); Seip, J. [Pennsylvania State Univ., Hershey, PA (United States)] [and others

    1994-09-01

    The small nuclear ribonucleoprotein-associated protein SmN (SNRPN) gene is located in the Prader-Willi syndrome (PWS) critical region in chromosome 15q11-q13. We have previously shown that it is functionally imprinted in humans, being only expressed from the paternal allele and differentially methylated on parental alleles. Therefore, SNRPN may have a role in PWS, although genetic studies suggest that at least two genes may be necessary for the classical PWS phenotype. We have characterized the SNRPN genomic structure, and shown that it comprises ten exons. Surprisingly, we identified an open reading frame (ORF) in the first three exons, 190-bp 5{prime} to the SmN ORF. Notably, the majority of base substitutions bewteen human and rodents in the upstream ORF occurred in the wobble position of codons, suggesting selection for a protein coding function. This ORF, which we name SNURF (SNRPN upstream reading frame) encodes a putative polypeptide of 71 amino acids. By analogy to prokaryotic operons that encode proteins with related functions, it is possible that SNURF may have a role in pre-mRNA splicing.

  12. Altered functional brain networks in Prader–Willi syndrome

    OpenAIRE

    Zhang, Yi; Zhao, Heng; Qiu, Siyou; Tian, Jie; Wen, Xiaotong; Miller, Jennifer L.; von Deneen, Karen M.; Zhou, Zhenyu; Gold, Mark S.; Liu, Yijun

    2013-01-01

    Prader–Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniqu...

  13. Epigenetics and Bruxism: Possible Role of Epigenetics in the Etiology of Bruxism.

    Science.gov (United States)

    Čalić, Aleksandra; Peterlin, Borut

    2015-01-01

    Bruxism is defined as a repetitive jaw muscle activity characterized by clenching or grinding of the teeth and/or bracing or thrusting of the mandible. There are two distinct circadian phenotypes for bruxism: sleep bruxism (SB) and awake bruxism, which are considered separate entities due to the putative difference in their etiology and phenotypic variance. The detailed etiology of bruxism so far remains unknown. Recent theories suggest the central regulation of certain pathophysiological or psychological pathways. Current proposed causes of bruxism appear to be a combination of genetic and environmental (G×E) factors, with epigenetics providing a robust framework for investigating G×E interactions, and their involvement in bruxism makes it a suitable candidate for epigenetic research. Both types of bruxism are associated with certain epigenetically determined disorders, such as Rett syndrome (RTT), Prader-Willi syndrome (PWS), and Angelman syndrome (AS), and these associations suggest a mechanistic link between epigenetic deregulation and bruxism. The present article reviews the possible role of epigenetic mechanisms in the etiology of both types of bruxism based on the epigenetic pathways involved in the pathophysiology of RTT, PWS, and AS, and on other epigenetic disruptions associated with risk factors for bruxism, including sleep disorders, altered stress response, and psychopathology.

  14. High rates of de novo 15q11q13 inversions in human spermatozoa

    Directory of Open Access Journals (Sweden)

    Molina Òscar

    2012-02-01

    Full Text Available Abstract Low-Copy Repeats predispose the 15q11-q13 region to non-allelic homologous recombination. We have already demonstrated that a significant percentage of Prader-Willi syndrome (PWS fathers have an increased susceptibility to generate 15q11q13 deletions in spermatozoa, suggesting the participation of intrachromatid exchanges. This work has been focused on assessing the incidence of de novo 15q11q13 inversions in spermatozoa of control donors and PWS fathers in order to determine the basal rates of inversions and to confirm the intrachromatid mechanism as the main cause of 15q11q13 anomalies. Semen samples from 10 control donors and 16 PWS fathers were processed and analyzed by triple-color FISH. Three differentially labeled BAC-clones were used: one proximal and two distal of the 15q11-q13 region. Signal associations allowed the discrimination between normal and inverted haplotypes, which were confirmed by laser-scanning confocal microscopy. Two types of inversions were detected which correspond to the segments involved in Class I and II PWS deletions. No significant differences were observed in the mean frequencies of inversions between controls and PWS fathers (3.59% ± 0.46 and 9.51% ± 0.87 vs 3.06% ± 0.33 and 10.07% ± 0.74. Individual comparisons showed significant increases of inversions in four PWS fathers (P Results suggest that the incidence of heterozygous inversion carriers in the general population could reach significant values. This situation could have important implications, as they have been described as predisposing haplotypes for genomic disorders. As a whole, results confirm the high instability of the 15q11-q13 region, which is prone to different types of de novo reorganizations by intrachromatid NAHR.

  15. VG2 J/S/U/N/SS PWS EDITED SPECTRUM ANALYZER FULL RES V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set includes nearly all measurements collected from the spectrum analyzer component of the Plasma Wave Spectrometer (PWS) onboard Voyager 2 for the entire...

  16. Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

    Science.gov (United States)

    Ornoy, Asher; Weinstein-Fudim, Liza; Ergaz, Zivanit

    2016-01-01

    Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others. Among the maternal diseases in pregnancy associated with ASD are diabetes mellitus (PGDM and/or GDM), some maternal autoimmune diseases like antiphospholipid syndrome (APLS) with anti-β2GP1 IgG antibodies and thyroid disease with anti-thyroid peroxidase (TPO) antibodies, preeclampsia and some other autoimmune diseases with IgG antibodies that might affect fetal brain development. Other related factors are maternal infections (rubella and CMV with fetal brain injuries, and possibly Influenza with fever), prolonged fever and maternal inflammation, especially with changes in a variety of inflammatory cytokines and antibodies that cross the placenta and affect the fetal brain. Among the drugs are valproic acid, thalidomide, misoprostol, and possibly SSRIs. β2-adrenergic receptor agonists and paracetamol have also lately been associated with increased rate of ASD but the data is too preliminary and inconclusive. Associations were also described with ethanol, cocaine, and possibly heavy metals, heavy smoking, and folic acid deficiency. Recent studies show that heavy exposure to pesticides and air pollution, especially particulate matter ASD. Finally, we have to remember that many of the associations mentioned in this review are only partially proven, and not all are "clean" of different confounding factors. The

  17. Combination of PDT and topical angiogenic inhibitor for treatment of port wine stain (PWS) birthmarks: a novel approach

    Science.gov (United States)

    Yuan, Kaihua; Huang, Qiaobing; Huang, Zheng

    2009-06-01

    Port wine stain (PWS) birthmarks are a congenital cutaneous vascular malformation involving ecstatic post-capillary venules. Current standard treatment for PWS is the pulsed dye laser (PDL). Vascular-targeted photodynamic therapy (PDT) has been used for the treatment of PWS in China since the early 1990's. Both can achieve a certain degree of color blanching in various types of PWS lesions. However, the majority of PWS lesions require multiple treatments. Some PWS lesions can recur or become darker after successful treatment. Recently, it has been proposed that this phenomenon might be initiated by neoangiogenesis that can be caused by treatment via wound healing response. The combined use of photothermolysis and a topical application of an angiogenic inhibitor such as Imiquimod and Rapamycin, were evaluated in several pilot studies. It is well-known that PDT can induce various host immune responses VEGF overexpression. Recent clinical data also show that improved clinical outcomes are obtained through the combination of ocular PDT and anti-VEGF therapy. This article will discuss rationales and implications of using such a combination modality and highlight recent progress based on our clinical experience and published data.

  18. Deletions of a differentially methylated CpG island at SNRPN define a putative imprinting control region

    Energy Technology Data Exchange (ETDEWEB)

    Sutcliffe, J.S.,; Nakao, M.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with paternal and maternal deficiencies, respectively, of gene expression within human chromosome 15q11-q13, and are caused by deletion, uniparental disomy, or other mutations. Four transcripts designated PAR-5, PAR-7, PAR-1 and PAR-4 were isolated and localized to a region within 300 kb telomeric to the gene encoding small nuclear ribonucleoprotein-associated polypeptide N (SNRPN). Analysis of the transcripts in cultured fibroblasts and lymphoblasts from deletion patients demonstrated that SNRPN, PAR-5 and PAR-1 are expressed exclusively from the paternal chromosome, defining an imprinted domain that spans at least 200 kb. All three imprinted transcripts were absent in cells from three PWS patients (one pair of sibs and one sporadic case) with small deletions that involve a differentially methylated CpG island containing a previously undescribed 5{prime} untranslated exon ({alpha}) of SNRPN. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. One deletion, which is benign when maternally transmitted, extends upstream <30 kb from the CpG island, and is associated with altered methylation centromeric to SNRPN, and loss of transcription telomeric to SNRPN, implying the presence of an imprinting control region around the CpG island containing exon {alpha}.

  19. Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation.

    Science.gov (United States)

    Delahanty, Ryan J; Zhang, Yanfeng; Bichell, Terry Jo; Shen, Wangzhen; Verdier, Kelienne; Macdonald, Robert L; Xu, Lili; Boyd, Kelli; Williams, Janice; Kang, Jing-Qiong

    2016-12-20

    Reduced ocular pigmentation is common in Angelman syndrome (AS) and Prader-Willi syndrome (PWS) and is long thought to be caused by OCA2 deletion. GABRB3 is located in the 15q11-13 region flanked by UBE3A, GABRA5, GABRG3, and OCA2. Mutations in GABRB3 have frequently been associated with epilepsy and autism, consistent with its role in neurodevelopment. We report here a robust phenotype in the mouse in which deletion of Gabrb3 alone causes nearly complete loss of retinal pigmentation due to atrophied melanosomes, as evidenced by electron microscopy. Using exome and RNA sequencing, we confirmed that only the Gabrb3 gene was disrupted while the Oca2 gene was intact. However, mRNA abundance of Oca2 and other genes adjacent to Gabrb3 is substantially reduced in Gabrb3 -/- mice, suggesting complex transcriptional regulation in this region. These results suggest that impairment in GABRB3 downregulates OCA2 and indirectly causes ocular hypopigmentation and visual defects in AS and PWS. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Chromosome 15q24 microdeletion syndrome

    Directory of Open Access Journals (Sweden)

    Magoulas Pilar L

    2012-01-01

    involves a multi-disciplinary approach to care with the primary care physician and clinical geneticist playing a crucial role in providing appropriate screening, surveillance, and care for individuals with this syndrome. At the time of diagnosis, individuals should receive baseline echocardiograms, audiologic, ophthalmologic, and developmental assessments. Growth and feeding should be closely monitored. Other specialists that may be involved in the care of individuals with 15q24 deletion syndrome include immunology, endocrine, orthopedics, neurology, and urology. Chromosome 15q24 microdeletion syndrome should be differentiated from other genetic syndromes, particularly velo-cardio-facial syndrome (22q11.2 deletion syndrome, Prader-Willi syndrome, and Noonan syndrome. These conditions share some phenotypic similarity to 15q24 deletion syndrome yet have characteristic features specific to each of them that allows the clinician to distinguish between them. Molecular genetic testing and/or aCGH will be able to diagnose these conditions in the majority of individuals. Disease name and synonyms Chromosome 15q24 deletion syndrome 15q24 deletion syndrome 15q24 microdeletion syndrome

  1. Malformation/dysplasia syndrome (neural tube defect, hypospadias neuroblastoma) associated with an extra dicentric marker chromosome 15 ({open_quotes}inversion duplication 15{close_quotes})

    Energy Technology Data Exchange (ETDEWEB)

    Reitnauer, P.J.; Rao, K.W.; Tepperberg, J.H. [Univ. of North Carolina, Chapel Hill, NC (United States)

    1994-09-01

    Extra dicentric 15 marker chromosomes are associated with variable degrees of mental retardation but not major structural birth defects. We have studied a unique patient, a male infant who was prenatally diagnosed with lumbar meningomyelocele and an extra pseudodicentric marker chromosome: 47,XY,+psu dic(15)t(15;15)(?q12,?q12)mat. Hairy ears and a coronal hypospadias were noted at birth. At three months of age, a stage I thoracic neuroblastoma was primarily resected. Tumor cells, skin fibroblasts and peripheral blood lymphocytes contained the dicentric 15. The mother is mosaic for the marker chromosome. Fluorescence in situ hybridization (FISH) studies using a classic 15 satellite probe (D15Z1 [Oncor]) confirmed the presence of 2 number 15 centromeres in the marker. The marker is felt to be the result of a translocation rather than an inverted duplication because the G-band morphology of the short arm/satellite complexes differ from one another, implying that the arms originate from 2 different number 15s. FISH analysis using cosmid probes for the Prader-Willi/Angelman critical region (D15S11 and GABRB3 [Oncor]) revealed 2 copies of this region, indicating that these loci are duplicated in the marker. Although some features of the patient`s phenotype such as developmental delay and hypotonia have been associated with dicentric chromosome 15 markers, this is the first malformation/dysplasia syndrome or neuroblastoma reported to our knowledge. The association of neuroblastoma with chromosome 15 aberrations in this case provides speculation as to the role of chromosome 15 loci in cell division control.

  2. Author Details - African Journals Online

    African Journals Online (AJOL)

    Thabet, NS. Vol 13, No 1 (2012) - Articles Modulation of back geometry in children with spastic diplegic cerebral palsy via hippotherapy training. Abstract PDF · Vol 14, No 3 (2013) - Articles Conservative therapy versus intra-gastric balloon in treatment of Prader-Willi Syndrome morbid obesity. Abstract PDF. ISSN: 1110- ...

  3. Increased Exposure to Rigid Routines Can Lead to Increased Challenging Behavior Following Changes to Those Routines

    Science.gov (United States)

    Bull, Leah E.; Oliver, Chris; Callaghan, Eleanor; Woodcock, Kate A.

    2015-01-01

    Several neurodevelopmental disorders are associated with preference for routine and challenging behavior following changes to routines. We examine individuals with Prader-Willi syndrome, who show elevated levels of this behavior, to better understand how previous experience of a routine can affect challenging behavior elicited by disruption to…

  4. A Neonate with persistent hypoglycemia and seizures.

    African Journals Online (AJOL)

    MBY

    disorder was diagnosed and managed with limited success as the episodes hydroglycemic seizures persisted. ... the presence of hyperinsulinemia as the cause of the hypoglycemic dependent seizures. Case Presentation. A three day old girl was admitted to the neonatal .... the Prader-Willi syndrome, has been reported.

  5. Hypocretin deficiency : neuronal loss and functional consequences

    NARCIS (Netherlands)

    Fronczek, Rolf

    2008-01-01

    The first part deals with the hypothalamic hypocretin system in disorders that are accompanied by narcolepsy-like sleep disturbances, i.e. Prader-Willi Syndrome, Parkinson’s Disease and Huntington’s Disease. To determine whether the hypocretin system is affected in these disorders, the total number

  6. Transdisciplinary Intervention by an Itinerant School Nurse in Two Rural Classrooms.

    Science.gov (United States)

    Stile, Stephen W.; Bentley, Nona

    1988-01-01

    Reports two transdisciplinary interventions conducted by an Itinerant school nurse. The case studies presented involve a Prader-Willi syndrome student enrolled in a class for the trainable mentally handicapped and a student enrolled in a regular fourth grade classroom but considered at risk for placement in a behavior disorders setting. (JHZ)

  7. Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.

    Science.gov (United States)

    Zhang, Chenhong; Yin, Aihua; Li, Hongde; Wang, Ruirui; Wu, Guojun; Shen, Jian; Zhang, Menghui; Wang, Linghua; Hou, Yaping; Ouyang, Haimei; Zhang, Yan; Zheng, Yinan; Wang, Jicheng; Lv, Xiaofei; Wang, Yulan; Zhang, Feng; Zeng, Benhua; Li, Wenxia; Yan, Feiyan; Zhao, Yufeng; Pang, Xiaoyan; Zhang, Xiaojun; Fu, Huaqing; Chen, Feng; Zhao, Naisi; Hamaker, Bruce R; Bridgewater, Laura C; Weinkove, David; Clement, Karine; Dore, Joel; Holmes, Elaine; Xiao, Huasheng; Zhao, Guoping; Yang, Shengli; Bork, Peer; Nicholson, Jeremy K; Wei, Hong; Tang, Huiru; Zhang, Xiaozhuang; Zhao, Liping

    2015-08-01

    Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children

  8. SnoRNA Snord116 (Pwcr1/MBII-85 deletion causes growth deficiency and hyperphagia in mice.

    Directory of Open Access Journals (Sweden)

    Feng Ding

    Full Text Available Prader-Willi syndrome (PWS is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a approximately 4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85 in PWS. To test this hypothesis, we created a approximately 150 kb deletion of the > 40 copies of Snord116 (Pwcr1/MBII-85 in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.

  9. Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits.

    Science.gov (United States)

    Maillard, Julien; Park, Soyoung; Croizier, Sophie; Vanacker, Charlotte; Cook, Joshua H; Prevot, Vincent; Tauber, Maithe; Bouret, Sebastien G

    2016-08-01

    Prader-Willi syndrome (PWS) is a genetic disorder characterized by a variety of physiological and behavioral dysregulations, including hyperphagia, a condition that can lead to life-threatening obesity. Feeding behavior is a highly complex process with multiple feedback loops that involve both peripheral and central systems. The arcuate nucleus of the hypothalamus (ARH) is critical for the regulation of homeostatic processes including feeding, and this nucleus develops during neonatal life under of the influence of both environmental and genetic factors. Although much attention has focused on the metabolic and behavioral outcomes of PWS, an understanding of its effects on the development of hypothalamic circuits remains elusive. Here, we show that mice lacking Magel2, one of the genes responsible for the etiology of PWS, display an abnormal development of ARH axonal projections. Notably, the density of anorexigenic α-melanocyte-stimulating hormone axons was reduced in adult Magel2-null mice, while the density of orexigenic agouti-related peptide fibers in the mutant mice appeared identical to that in control mice. On the basis of previous findings showing a pivotal role for metabolic hormones in hypothalamic development, we also measured leptin and ghrelin levels in Magel2-null and control neonates and found that mutant mice have normal leptin and ghrelin levels. In vitro experiments show that Magel2 directly promotes axon growth. Together, these findings suggest that a loss of Magel2 leads to the disruption of hypothalamic feeding circuits, an effect that appears to be independent of the neurodevelopmental effects of leptin and ghrelin and likely involves a direct neurotrophic effect of Magel2. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. A prospective study of risk for Sturge-Weber syndrome in children with upper facial port-wine stain.

    Science.gov (United States)

    Dutkiewicz, Anne-Sophie; Ezzedine, Khaled; Mazereeuw-Hautier, Juliette; Lacour, Jean-Philippe; Barbarot, Sébastien; Vabres, Pierre; Miquel, Juliette; Balguerie, Xavier; Martin, Ludovic; Boralevi, Franck; Bessou, Pierre; Chateil, Jean-François; Léauté-Labrèze, Christine

    2015-03-01

    Upper facial port-wine stain (PWS) is a feature of Sturge-Weber syndrome (SWS). Recent studies suggest that the distribution of the PWS corresponds to genetic mosaicism rather than to trigeminal nerve impairment. We sought to refine the cutaneous distribution of upper facial PWS at risk for SWS. This was a prospective multicenter study of consecutive cases of upper facial PWS larger than 1 cm² located in the ophthalmic division of trigeminal nerve distribution in infants aged less than 1 year, seen in 8 French pediatric dermatology departments between 2006 and 2012. Clinical data, magnetic resonance imaging, and photographs were systematically collected and studied. PWS were classified into 6 distinct patterns. In all, 66 patients were included. Eleven presented with SWS (magnetic resonance imaging signs and seizure). Four additional infants had suspected SWS without neurologic manifestations. Hemifacial (odds ratio 7.7, P = .003) and median (odds ratio 17.08, P = .008) PWS patterns were found to be at high risk for SWS. A nonmedian linear pattern was not associated with SWS. Small number of patients translated to limited power of the study. Specific PWS distribution patterns are associated with an increased risk of SWS. These PWS patterns conform to areas of somatic mosaicism. Terminology stipulating ophthalmic division of trigeminal nerve territory involvement in SWS should be abandoned. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  11. Role of ghrelin in the pathophysiology of eating disorders: implications for pharmacotherapy.

    Science.gov (United States)

    Cardona Cano, Sebastian; Merkestein, Myrte; Skibicka, Karolina P; Dickson, Suzanne L; Adan, Roger A H

    2012-04-01

    Ghrelin is the only known circulating orexigenic hormone. It increases food intake by interacting with hypothalamic and brainstem circuits involved in energy balance, as well as reward-related brain areas. A heightened gut-brain ghrelin axis is an emerging feature of certain eating disorders such as anorexia nervosa and Prader-Willi syndrome. In common obesity, ghrelin levels are lowered, whereas post-meal ghrelin levels remain higher than in lean individuals. Agents that interfere with ghrelin signalling have therapeutic potential for eating disorders, including obesity. However, most of these drugs are only in the preclinical phase of development. Data obtained so far suggest that ghrelin agonists may have potential in the treatment of anorexia nervosa, while ghrelin antagonists seem promising for other eating disorders such as obesity and Prader-Willi syndrome. However, large clinical trials are needed to evaluate the efficacy and safety of these drugs.

  12. Biological effects of diethylene glycol (DEG) and produced waters (PWs) released from offshore activities: a multi-biomarker approach with the sea bass Dicentrarchus labrax.

    Science.gov (United States)

    Stefania, Gorbi; Maura, Benedetti; Claudia, Virno Lamberti; Barbara, Pisanelli; Ginevra, Moltedo; Francesco, Regoli

    2009-11-01

    Diethylene glycol (DEG) is largely used during oil and gas exploitation by offshore platforms. The aim of this work was to investigate if this compound induces direct molecular/cellular effects in marine organisms, or indirectly modulate those of produced waters (PWs). Sea bass (Dicentrarchus labrax) were exposed to DEG dosed alone or in combination with PWs from an Adriatic platform. A wide array of analysed biomarkers included cytochrome P450-dependent enzymatic activity, bile metabolites, glutathione S-transferases, acetylcholinesterase, peroxisomal proliferation, antioxidant defences (catalase, glutathione reductase, glutathione peroxidases, glutathione), total oxyradical scavenging capacity, malondialdehyde and DNA integrity (single strand breaks and frequency of micronuclei). Results did not reveal marked effects of DEG, while PWs influenced the biotransformation system, the oxidative status and the onset of genotoxic damages. Co-exposures caused only limited differences of biomarker responses at some experimental conditions, overall suggesting a limited biological impact of DEG at levels normally deriving from offshore activities.

  13. Prader–Willi syndrome: clinical problems in transition from pediatric to adult care

    OpenAIRE

    Crinò A; Fintini D; Bocchini S; Carducci C; Grugni G

    2016-01-01

    Antonino Crinò,1 Danilo Fintini,1 Sarah Bocchini,1 Chiara Carducci,1 Graziano Grugni,2 1Autoimmune Endocrine Diseases Unit, Bambino Gesù Children’s Hospital, Research Institute, Palidoro, Rome, 2Division of Auxology, Italian Auxological Institute, Research Institute, Piancavallo, Verbania, Italy Abstract: Prader–Willi syndrome (PWS) represents the most common form of genetic obesity. Thanks to the advances in medical care and technology, many persons with PWS li...

  14. Stem Cell Technology for (Epi)genetic Brain Disorders.

    Science.gov (United States)

    Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

    2017-01-01

    Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

  15. Clinical management of behavioral characteristics of Prader–Willi syndrome

    Directory of Open Access Journals (Sweden)

    Alan Y Ho

    2010-04-01

    Full Text Available Alan Y Ho, Anastasia DimitropoulosDepartment of Psychology, Case Western Reserve University, Cleveland, OH, USAAbstract: Prader–Willi syndrome (PWS is a complex neurodevelopmental disorder caused by an abnormality on the long arm of chromosome 15 (q11–q13 that results in a host of phenotypic characteristics, dominated primarily by hyperphagia and insatiable appetite. Characteristic behavioral disturbances in PWS include excessive interest in food, skin picking, difficulty with a change in routine, temper tantrums, obsessive and compulsive behaviors, and mood fluctuations. Individuals with PWS typically have intellectual disabilities (borderline to mild/moderate mental retardation and exhibit a higher overall behavior disturbance compared to individuals with similar intellectual disability. Due to its multisystem disorder, family members, caregivers, physicians, dieticians, and speech-language pathologists all play an important role in the management and treatment of symptoms in an individual with PWS. This article reviews current research on behavior and cognition in PWS and discusses management guidelines for this disorder.Keywords: Prader–Willi syndrome; neurodevelopment, hyperphagia, disability

  16. Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader–Willi syndrome

    Directory of Open Access Journals (Sweden)

    Ibrahim Knani

    2016-12-01

    Full Text Available Objective: Extreme obesity is a core phenotypic feature of Prader–Willi syndrome (PWS. Among numerous metabolic regulators, the endocannabinoid (eCB system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects. Methods: We studied eCB ‘tone’ in individuals with PWS and in the Magel2-null mouse model that recapitulates the major metabolic phenotypes of PWS and determined the efficacy of a peripherally restricted CB1R antagonist, JD5037 in treating obesity in these mice. Results: Individuals with PWS had elevated circulating levels of 2-arachidonoylglycerol and its endogenous precursor and breakdown ligand, arachidonic acid. Increased hypothalamic eCB ‘tone’, manifested by increased eCBs and upregulated CB1R, was associated with increased fat mass, reduced energy expenditure, and decreased voluntary activity in Magel2-null mice. Daily chronic treatment of obese Magel2-null mice and their littermate wild-type controls with JD5037 (3 mg/kg/d for 28 days reduced body weight, reversed hyperphagia, and improved metabolic parameters related to their obese phenotype. Conclusions: Dysregulation of the eCB/CB1R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB1R antagonists may be an effective strategy for the management of severe obesity in PWS. Author Video: Author Video Watch what authors say about their articles Keywords: Endocannabinoids, PWS, Magel2, Peripheral CB1 blockade, Metabolic syndrome

  17. Biological effects of diethylene glycol (DEG) and produced waters (PWs) released from offshore activities: A multi-biomarker approach with the sea bass Dicentrarchus labrax

    Energy Technology Data Exchange (ETDEWEB)

    Stefania, Gorbi; Maura, Benedetti [Dipartimento di Biochimica, Biologia e Genetica, Universita Politecnica delle Marche, Via Ranieri, Monte d' Ago, 60121 Ancona (Italy); Claudia, Virno Lamberti [Istituto Superiore per la Ricerca e la Protezione Ambientale (ISPRA), Via di Casalotti 300 Roma (Italy); Barbara, Pisanelli [Dipartimento di Biochimica, Biologia e Genetica, Universita Politecnica delle Marche, Via Ranieri, Monte d' Ago, 60121 Ancona (Italy); Ginevra, Moltedo [Istituto Superiore per la Ricerca e la Protezione Ambientale (ISPRA), Via di Casalotti 300 Roma (Italy); Francesco, Regoli, E-mail: f.regoli@univpm.i [Dipartimento di Biochimica, Biologia e Genetica, Universita Politecnica delle Marche, Via Ranieri, Monte d' Ago, 60121 Ancona (Italy)

    2009-11-15

    Diethylene glycol (DEG) is largely used during oil and gas exploitation by offshore platforms. The aim of this work was to investigate if this compound induces direct molecular/cellular effects in marine organisms, or indirectly modulate those of produced waters (PWs). Sea bass (Dicentrarchus labrax) were exposed to DEG dosed alone or in combination with PWs from an Adriatic platform. A wide array of analysed biomarkers included cytochrome P450-dependent enzymatic activity, bile metabolites, glutathione S-transferases, acetylcholinesterase, peroxisomal proliferation, antioxidant defences (catalase, glutathione reductase, glutathione peroxidases, glutathione), total oxyradical scavenging capacity, malondialdehyde and DNA integrity (single strand breaks and frequency of micronuclei). Results did not reveal marked effects of DEG, while PWs influenced the biotransformation system, the oxidative status and the onset of genotoxic damages. Co-exposures caused only limited differences of biomarker responses at some experimental conditions, overall suggesting a limited biological impact of DEG at levels normally deriving from offshore activities. - A biological risk for marine organisms can be excluded for DEG concentrations as those normally associated to produced waters discharged in the Adriatic Sea.

  18. Biological effects of diethylene glycol (DEG) and produced waters (PWs) released from offshore activities: A multi-biomarker approach with the sea bass Dicentrarchus labrax

    International Nuclear Information System (INIS)

    Stefania, Gorbi; Maura, Benedetti; Claudia, Virno Lamberti; Barbara, Pisanelli; Ginevra, Moltedo; Francesco, Regoli

    2009-01-01

    Diethylene glycol (DEG) is largely used during oil and gas exploitation by offshore platforms. The aim of this work was to investigate if this compound induces direct molecular/cellular effects in marine organisms, or indirectly modulate those of produced waters (PWs). Sea bass (Dicentrarchus labrax) were exposed to DEG dosed alone or in combination with PWs from an Adriatic platform. A wide array of analysed biomarkers included cytochrome P450-dependent enzymatic activity, bile metabolites, glutathione S-transferases, acetylcholinesterase, peroxisomal proliferation, antioxidant defences (catalase, glutathione reductase, glutathione peroxidases, glutathione), total oxyradical scavenging capacity, malondialdehyde and DNA integrity (single strand breaks and frequency of micronuclei). Results did not reveal marked effects of DEG, while PWs influenced the biotransformation system, the oxidative status and the onset of genotoxic damages. Co-exposures caused only limited differences of biomarker responses at some experimental conditions, overall suggesting a limited biological impact of DEG at levels normally deriving from offshore activities. - A biological risk for marine organisms can be excluded for DEG concentrations as those normally associated to produced waters discharged in the Adriatic Sea.

  19. Linguagem e alimentação em casos de Prader-Willi e Kabuki: trabalho fonoaudiológico em oficina de cozinha

    OpenAIRE

    Zambotti, Nathalia

    2011-01-01

    Estudos recentes da clínica fonoaudiológica infantil têm apontado coocorrência sistemática de problemas de linguagem e de alimentação, tratando as questões fonoaudiológicas ligadas a zona oral sob o conceito de oralidade (GOLSE; GUINOT, 2004). Supõe-se que a boca é território de alimentação, linguagem e afetos (PALLADINO; CUNHA; SOUZA, 2007). O dispositivo terapêutico proposto, a Oficina de Cozinha, tem se mostrado pertinente para crianças com problemas de linguagem, poi...

  20. Prader–Willi syndrome: clinical problems in transition from pediatric to adult care

    Directory of Open Access Journals (Sweden)

    Crinò A

    2016-07-01

    Full Text Available Antonino Crinò,1 Danilo Fintini,1 Sarah Bocchini,1 Chiara Carducci,1 Graziano Grugni,2 1Autoimmune Endocrine Diseases Unit, Bambino Gesù Children’s Hospital, Research Institute, Palidoro, Rome, 2Division of Auxology, Italian Auxological Institute, Research Institute, Piancavallo, Verbania, Italy Abstract: Prader–Willi syndrome (PWS represents the most common form of genetic obesity. Thanks to the advances in medical care and technology, many persons with PWS live longer and survive to adulthood. Currently, because of the many physical and behavioral manifestations, transitional health care is not easy for these patients and is considered a very important issue. Moreover, very few studies have examined these transitional problems in young adults with PWS. In recent years, there has been great interest in improving transition planning and support for young people with PWS reaching adulthood. In this article, we underline the main clinical problems in transition and give some advice to make this period less difficult and easier for adolescents with PWS. Special attention should be paid to obesity, diabetes mellitus, hypertension, osteoporosis, and sleep apnea during the period of transition. In PWS, for an effective transition from childhood to adulthood, a multidisciplinary team is needed, and should maintain the same approach to food, environment, and psychiatric issues. For comprehensive care, it is necessary to involve adult endocrinologists and other medical specialists in conjunction with the pediatric team. Parental involvement is, however, a great help for supervising adolescents with PWS during this particular period. Keywords: Prader–Willi, transition period, intellectual disabilities

  1. Highly restricted deletion of the SNORD116 region is implicated in Prader–Willi Syndrome

    Science.gov (United States)

    Bieth, Eric; Eddiry, Sanaa; Gaston, Véronique; Lorenzini, Françoise; Buffet, Alexandre; Conte Auriol, Françoise; Molinas, Catherine; Cailley, Dorothée; Rooryck, Caroline; Arveiler, Benoit; Cavaillé, Jérome; Salles, Jean Pierre; Tauber, Maïthé

    2015-01-01

    The SNORD116 locus lies in the 15q11-13 region of paternally expressed genes implicated in Prader–Willi Syndrome (PWS), a complex disease accompanied by obesity and severe neurobehavioural disturbances. Cases of PWS patients with a deletion encompassing the SNORD116 gene cluster, but preserving the expression of flanking genes, have been described. We report a 23-year-old woman who presented clinical criteria of PWS, including the behavioural and nutritional features, obesity, developmental delay and endocrine dysfunctions with hyperghrelinemia. We found a paternally transmitted highly restricted deletion of the SNORD116 gene cluster, the shortest described to date (118 kb). This deletion was also present in the father. This finding in a human case strongly supports the current hypothesis that lack of the paternal SNORD116 gene cluster has a determinant role in the pathogenesis of PWS. Moreover, targeted analysis of the SNORD116 gene cluster, complementary to SNRPN methylation analysis, should be carried out in subjects with a phenotype suggestive of PWS. PMID:24916642

  2. Sturge-Weber syndrome. The current neuro-imaging data

    International Nuclear Information System (INIS)

    Boukobza, M.; Cambra, M.R.; Merland, J.J.; Enjolras, O.

    2000-01-01

    Sturge-Weber syndrome (SWS) is a rare congenital sporadic disease with neuro-ocular and cutaneous vascular findings. Clinically, the full-blown condition consists of a facial port-wine stain (PWS) the V1 facial trigeminal skin area, alone or in combination with V2 and V3 PWS, seizures and ocular abnormalities (glaucoma and choroidal angioma). Radiologically, a leptomeningeal (pial) capillary and venous malformation, mostly located in the parieto-occipital area, cerebral atrophy and calcifications are demonstrated. An ipsilateral enlarged choroid plexus may be an early anatomic symptom. Development neuro-diagnostic technique for the screening of infants with an at-risk V1 PWS, as well as for the follow-up of patients with evidence SWS. Accelerated myelination in the involved hemisphere may be early diagnostic feature before 6 months of age. Later, hyperintensity of white matter on T2 is considered a symptom of gliosis. Clinically, progression of the diseases is associated with anatomic changes and correlates with the extent of the pial vascular anomaly, extent and severity of cerebral atrophy, and white matter abnormalities. A neonatal neuro-imaging work-up, using CT or MRI, may not demonstrate the pial anomaly and should be repeated after 6 to 12 months in an at-risk infant with V1 PWS. (authors)

  3. Obesity and dermatology.

    Science.gov (United States)

    Scheinfeld, Noah S

    2004-01-01

    Obesity is associated with a number of dermatoses. It affects cutaneous sensation, temperature regulation, foot shape, and vasculature. Acanthosis nigricans is the most common dermatological manifestation of obesity. Skin tags are more commonly associated with diabetes than with obesity. Obesity increases the incidence of cutaneous infections that include: candidiasis, intertigo, candida folliculitis, furunculosis, erythrasma, tinea cruris, and folliculitis. Less common infections include cellulitis, necrotizing fasciitis, and gas gangrene. Leg ulcerations, lymphedema, plantar hyperkeratosis, and striae are more common with obesity. Hormonal abnormalities and genetic syndromes (Prader-Willi) are related to obesity and its dermatoses; however, cellulite is not related to obesity.

  4. Growth hormone treatment in non-growth hormone-deficient children

    Directory of Open Access Journals (Sweden)

    Sandro Loche

    2014-03-01

    Full Text Available Until 1985 growth hormone (GH was obtained from pituitary extracts, and was available in limited amounts only to treat severe growth hormone deficiency (GHD. With the availability of unlimited quantities of GH obtained from recombinant DNA technology, researchers started to explore new modalities to treat GHD children, as well as to treat a number of other non-GHD conditions. Although with some differences between different countries, GH treatment is indicated in children with Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, deletions/mutations of the SHOX gene, as well as in short children born small for gestational age and with idiopathic short stature. Available data from controlled trials indicate that GH treatment increases adult height in patients with Turner syndrome, in patients with chronic renal insufficiency, and in short children born small for gestational age. Patients with SHOX deficiency seem to respond to treatment similarly to Turner syndrome. GH treatment in children with idiopathic short stature produces a modest mean increase in adult height but the response in the individual patient is unpredictable. Uncontrolled studies indicate that GH treatment may be beneficial also in children with Noonan syndrome. In patients with Prader-Willi syndrome GH treatment normalizes growth and improves body composition and cognitive function. In any indication the response to GH seems correlated to the dose and the duration of treatment. GH treatment is generally safe with no major adverse effects being recorded in any condition.

  5. Expanding the BP1-BP2 15q11.2 Microdeletion Phenotype: Tracheoesophageal Fistula and Congenital Cataracts

    Directory of Open Access Journals (Sweden)

    D. Wong

    2013-01-01

    Full Text Available The proximal q arm of chromosome 15 contains breakpoint regions BP1–BP5 with the classic deletion of BP1–BP3 best known to be associated with Prader-Willi and Angelman syndromes. The region is approximately 500 kb and microdeletions within the BP1-BP2 region have been reported in patients with developmental delay, behavioral abnormalities, and motor apraxia as well as dysmorphic features including hypertelorism, cleft or narrow palate, ear abnormalities, and recurrent upper airway infections. We report two patients with unique, never-before-reported 15q11.2 BP1-2 microdeletion syndrome findings, one with proximal esophageal atresia and distal tracheoesophageal fistula (type C and one with congenital cataracts. Cataracts have been described in Prader-Willi syndrome but we could not find any description of cataracts in Angelman syndrome. Esophageal atresia and tracheoesophageal fistula have not been reported to our knowledge in either syndrome. A chance exists that both cases are sporadic birth defects; however, the findings of the concomitant microdeletion cannot be overlooked as a possible cause. Based on our review of the literature and the presentation of our patients, we recommend that esophageal atresia and distal tracheoesophageal fistula as well as congenital cataracts be included in the phenotypic spectrum of 15q11.2 BP1-2 microdeletion syndrome.

  6. Energy Expenditure and Physical Activity in Prader–Willi Syndrome

    Science.gov (United States)

    Butler, Merlin G.; Theodoro, Mariana F.; Bittel, Douglas C.; Donnelly, Joseph E.

    2017-01-01

    Prader–Willi syndrome (PWS) is a complex neurodevelopmental disorder characterized by hypotonia, suck and feeding difficulties, hypogonadism, small hands and feet, developmental delay, hyperphagia and early childhood obesity and a particular facial appearance. The obesity associated with PWS is the result of a chronic imbalance between energy intake and energy expenditure (EE) due to hyperphagia, decreased physical activity, reduced metabolic rate and an inability to vomit. EE is affected by body composition as well as exercise. Individuals with PWS have a lower lean body mass (LBM) compared with controls which may contribute to reduced basal level EE. To determine the relationship among body composition, activity levels and metabolic rates, dual energy X-ray absorptiometry (DEXA) and a whole-room respiration chamber were used to measure body composition, total EE (TEE), resting EE (REE), physical activity, and mechanical work (MW) during an 8 hr monitoring period. The chamber consisted of a live-in whole-room indirect calorimeter equipped with a force platform floor to allow simultaneous measurement of EE, physical activity, and work efficiency during spontaneous activities and standardized exercise. Participants with PWS (27 with 15q11–q13 deletion and 21 with maternal disomy 15 with an average age of 23 years) had significantly decreased TEE by 20% and reduced LBM compared to 24 obese subjects. Similarly, REE was significantly reduced by 16% in the individuals with PWS relative to the comparison subjects. Total MW performed during the 8 hr monitoring period was significantly reduced by 35% in the PWS group. The energy cost of physical activity is related to the duration, intensity and type of activity and the metabolic efficiency of the individual. After adjusting group differences in LBM by analysis of variance, TEE and REE were no longer different between the two groups. Our data indicate that there is a significant reduction of EE in individuals with PWS

  7. Sturge-Weber syndrome. The current neuro-imaging data; Syndrome de Sturge-Weber. Donnees actuelles de l'imagerie neuroradiologique

    Energy Technology Data Exchange (ETDEWEB)

    Boukobza, M.; Cambra, M.R.; Merland, J.J.; Enjolras, O. [Hopital Lariboisiere, 75 - Paris (France)

    2000-07-01

    Sturge-Weber syndrome (SWS) is a rare congenital sporadic disease with neuro-ocular and cutaneous vascular findings. Clinically, the full-blown condition consists of a facial port-wine stain (PWS) the V1 facial trigeminal skin area, alone or in combination with V2 and V3 PWS, seizures and ocular abnormalities (glaucoma and choroidal angioma). Radiologically, a leptomeningeal (pial) capillary and venous malformation, mostly located in the parieto-occipital area, cerebral atrophy and calcifications are demonstrated. An ipsilateral enlarged choroid plexus may be an early anatomic symptom. Development neuro-diagnostic technique for the screening of infants with an at-risk V1 PWS, as well as for the follow-up of patients with evidence SWS. Accelerated myelination in the involved hemisphere may be early diagnostic feature before 6 months of age. Later, hyperintensity of white matter on T2 is considered a symptom of gliosis. Clinically, progression of the diseases is associated with anatomic changes and correlates with the extent of the pial vascular anomaly, extent and severity of cerebral atrophy, and white matter abnormalities. A neonatal neuro-imaging work-up, using CT or MRI, may not demonstrate the pial anomaly and should be repeated after 6 to 12 months in an at-risk infant with V1 PWS. (authors)

  8. Ontogenesis of oxytocin pathways in the mammalian brain: late maturation and psychosocial disorders

    Directory of Open Access Journals (Sweden)

    Valery eGrinevich

    2015-01-01

    Full Text Available Oxytocin (OT, the main neuropeptide of sociality, is expressed in neurons exclusively localized in the hypothalamus. During the last decade, a plethora of neuroendocrine, metabolic, autonomic and behavioral effects of OT has been reported. In the urgency to find treatments to syndromes as invalidating as autism, many clinical trials have been launched in which OT is administered to patients, including adolescents and children. However, the impact of OT on the developing brain and in particular on the embryonic and early postnatal maturation of OT neurons, has been only poorly investigated. In the present review we summarize available (although limited literature on general features of ontogenetic transformation of the OT system, including determination, migration and differentiation of OT neurons. Next, we discuss trajectories of OT receptors (OTR in perinatal period. Furthermore, we provide evidence that early alterations, from birth, in the central OT system lead to severe neurodevelopmental diseases such as feeding deficit in infancy and severe defects in social behavior in adulthood, as described in Prader-Willi syndrome. Our review intends to propose a hypothesis about developmental dynamics of central OT pathways, which are essential for survival right after birth and for the acquisition of social skills later on. A better understanding of the embryonic and early postnatal maturation of the OT system may lead to better OT-based treatments in Prader-Willi syndrome and autism.

  9. GAMBARAN CAKUPAN PELAYANAN KESEHATAN MATERNAL DAN NEONATAL PADA PESERTA JAMINAN KESEHATAN MASYARAKAT MISKIN DI PROVINSI JAWA BARAT (ANALISIS DATA PWS KIA DAN JPSBK TAHUN 2004

    Directory of Open Access Journals (Sweden)

    Wahyu P. Nugraheni

    2012-11-01

    Full Text Available The Maternal Mortality Rate in Indonesia was 373/100.000 per live birth (SDKI 2002. It is the highest in South East Asia. The Infant Mortality Rate was 40/1000 per live birth, the highest compared among ASEAN countries. The Human Development Index In West Java year 2002 was 0.658 and at 17th rank out of 30 provinces which was better than East Java in which at 25th. But rank was higher compared with others provinces in Java-Bali: Banten, Bali, Central Java, DI Jogjakarta, and DKI Jakarta. The Jaminan Kesehatan Masyarakat Miskin (JKMM is an intervention program  to increase economic gap and to achieve higher coverage of childbirth care by midwives for the poor families. In the other side, there was no information on the influence of JKMM to coverage of childbirth care by midwives for the poor families, esspecially the information about moving up of childbirth care from traditional birth attendants (TBA to midwives. The research was an evaluation study with across sectional approach. The research was done at 3 Districts in West Java (Garut, Sumedang and Sukabumi. The data consist of secondary data (PWS KIA and primer data (by in-depth interview. The Bivariate Analysis was done on the secondary data to determine factors that related between independent variable and dependent variable. Results of the research showed that there were no significant different between coverage of childbirth care by midwives (LINAKES at health centers with the higher poor proportion people and the lower poor proportion people groups. It showed that the JKMM program not different in the coverage childbirth care by midwives between the poor people and the non­ poor people. The geographic factors (longer distance, cost of transportation, longer time from village to health center were significant different in childbirth care by midwives. The health centers with good geographic conditions had better coverages of childbirth by midwives compared with the health center with

  10. Valutazione di efficienza nella somministrazione dell’ormone della crescita (GH

    Directory of Open Access Journals (Sweden)

    Federico Spandonaro

    2013-03-01

    Full Text Available Treatment with growth hormone (somatropin is effective in six different medical conditions: growth hormone deficiency (GHD, Turner syndrome (TS, growth retardation in children born small for gestational age (SGA, Prader-Willi syndrome (PWS, growth retardation due to chronic renal insufficiency (CRI, growth retardation associated with a deficiency of the gene SHOX (Short Stature HOmeoboXContaining gene. The treatment proved to be also effective in adults who have an impaired growth hormone (acquired in adulthood or childhood.The growth hormone (GH is generally cost effective and, therefore, is usually reimbursed by public health services. In financial terms, GH is a major cost item for health systems. According to the Report OSMED 2010, GH ranks first in Italy between systemic hormonal preparations, excluding sex hormones, distributed by public system, with an annual value of approximately € 88 million (+ 12.7% compared to 2009.Considering the increasing need to control pharmaceutical expenditure, there is a strong interest for the efficient supply of the hormone by the regional health service. From this point of view, the comparison of the specialties on the market is normally carried out on the basis of the cost per mg; this approach, also used in the main studies of cost-effectiveness, is derived from a logic of cost minimization, but it may still be distorting, not taking into account the efficiency of devices used for the administration of the hormone.The proposed analysis verifies the efficiency of different available devices, evaluating the potential waste of product, depending both on the device used and on the characteristics of the population exposed to the treatment.Only in the case of single-dose and disposable formulations is theoretically possible to have zero waste and thus an equivalence between the actual cost of the treatment and the price charged. In other cases, the inefficiency causes a deviation between the actual cost and

  11. Prader–Willi syndrome: clinical problems in transition from pediatric to adult care

    OpenAIRE

    Crinò, Antonino; Fintini,Danilo; Bocchini,Sarah; Carducci,Chiara; Grugni,Graziano

    2016-01-01

    Antonino Crinò,1 Danilo Fintini,1 Sarah Bocchini,1 Chiara Carducci,1 Graziano Grugni,2 1Autoimmune Endocrine Diseases Unit, Bambino Gesù Children’s Hospital, Research Institute, Palidoro, Rome, 2Division of Auxology, Italian Auxological Institute, Research Institute, Piancavallo, Verbania, Italy Abstract: Prader–Willi syndrome (PWS) represents the most common form of genetic obesity. Thanks to the advances in medical care and technology, many...

  12. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    Science.gov (United States)

    Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George

    2016-01-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

  13. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders.

    Directory of Open Access Journals (Sweden)

    Anthony R Isles

    2016-05-01

    Full Text Available Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS region have been associated with developmental delay (DD, autism spectrum disorder (ASD and schizophrenia (SZ. Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA, but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15 or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of

  14. Pyogenic Granuloma in a Patient of Sturge-Weber Syndrome with Bilateral Port Wine Stain- A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Shantala Arunkumar

    2014-07-01

    Full Text Available Sturge-Weber syndrome (SWS also known as encephalotrigeminal angiomatosis. It is a neurocutaneous syndrome, characterized by a facial vascular birthmark and neurological abnormalities. An ipsilateral or bilateral facial cutaneous vascular malformation Port Wine Stain (PWS usually affects the upper face. Other clinical manifestations are seizures, glaucoma, hemiparesis, mental retardation and delayed developmental milestones. The main objective of this case report is to unravel such a rarest syndrome with bilateral port-wine stain, which has intraoral manifestation of pyogenic granuloma involving gingiva in an 11 year old boy.

  15. Epigenetics, autism spectrum, and neurodevelopmental disorders.

    Science.gov (United States)

    Rangasamy, Sampathkumar; D'Mello, Santosh R; Narayanan, Vinodh

    2013-10-01

    Epigenetic marks are modifications of DNA and histones. They are considered to be permanent within a single cell during development, and are heritable across cell division. Programming of neurons through epigenetic mechanisms is believed to be critical in neural development. Disruption or alteration in this process causes an array of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Recent studies have provided evidence for an altered epigenetic landscape in ASDs and demonstrated the central role of epigenetic mechanisms in their pathogenesis. Many of the genes linked to the ASDs encode proteins that are involved in transcriptional regulation and chromatin remodeling. In this review we highlight selected neurodevelopmental disorders in which epigenetic dysregulation plays an important role. These include Rett syndrome, fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, and Kabuki syndrome. For each of these disorders, we discuss how advances in our understanding of epigenetic mechanisms may lead to novel therapeutic approaches.

  16. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  17. Necdin, a Prader–Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development

    Science.gov (United States)

    Miller, Nichol L.G.; Wevrick, Rachel; Mellon, Pamela L.

    2009-01-01

    Prader–Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS. PMID:18930956

  18. Cataplexy leading to the diagnosis of Niemann-Pick disease type C.

    Science.gov (United States)

    Smit, Liesbeth S; Lammers, Gert Jan; Catsman-Berrevoets, Coriene E

    2006-07-01

    Cataplexy in childhood is a rare and often misdiagnosed symptom. It is described as a brief episode of bilateral loss of muscle tone with intact consciousness, triggered by a variety of strong emotions and in particular with unexpected laughter. This report presents a 9-year old male with progressive cerebellar and pyramidal symptoms and a cognitive decline since the age of 4. His recently developed "drop attacks" on laughter were recognized as cataplexy and led to the diagnosis of Niemann-Pick type C disease. With biochemical studies this diagnosis, a lysosomal storage disease, was confirmed. With cataplexy narcolepsy, Niemann-Pick type C disease, Norrie disease, Prader-Willi syndrome, and Coffin-Lowry syndrome are associated disorders. Recognition of cataplexy in children with concomitant neurologic symptoms may lead to an early and straight diagnosis of one of these disorders.

  19. Beals Syndrome

    Science.gov (United States)

    ... the syndrome. How does Beals syndrome compare with Marfan syndrome? People with Beals syndrome have many of the ... bone) and aortic enlargement problems as people with Marfan syndrome, and treatments for these problems are the same. ...

  20. Nutritient intake of young children with Prader–Willi syndrome

    Directory of Open Access Journals (Sweden)

    Marianne Lindmark

    2010-03-01

    Full Text Available Background: Prader–Willi syndrome (PWS is a rare genetic disorder resulting in obesity. The diets for young children with PWS must balance the importance of preventing development of obesity with the need to supply sufficient energy and essential nutrients. Objective: To investigate the nutritional intake for children with PWS 2, 3, and 4 years of age and compare it with Nordic Nutritional Recommendations (NNR and intake of healthy controls. Design: Assessments of food intake for six children 2–4 years of age were performed twice a year. At the age of 2 and 3 years data was obtained by using food recall interviews and at 4 year of age a pre-coded food-diary was used. Results: The energy intake for the 2-year-old children was 3.25 MJ/day (SD 0.85 and for the 3- and 4-year olds 3.62 MJ/day (SD 0.73 and 4.07 MJ/day (SD 0.39 MJ, respectively. These intakes are 61%, 68%, and 77% of the estimated energy requirements in NNR for healthy 2-, 3- and 4-year-old children, respectively, and 60% and 66% of the energy intakes of 2- and 4-year-old children in reference populations. The children's BMI-for-age score and length growth was within the normal range during the study period. The intake of fat was about 25 E% in all age groups and reduced when compared with reference populations. In 25% of the assessments the fat intake was 20 E% or below. The intake of iron was below recommendations in all age groups both with and without supplementation. The mean intake of vitamin D and tocopherol was below recommendations when intakes were determined excluding dietary supplementations. Conclusions: More large-scale investigations on nutritional intake are needed to further investigate dietary challenges for this patient group.

  1. First Case Report of Prader–Willi-Like Syndrome in Colombia

    Directory of Open Access Journals (Sweden)

    Estephania Candelo

    2018-03-01

    Full Text Available Background: Prader–Willi-like syndrome (PWLS is believed to be caused by a variety of disruptions in genetic pathways both inside and outside of the genetic region implicated in PWS. By definition, PWLS does not demonstrate mutations in the 15q11–q13 region itself. It is a rare disorder whose clinical hallmarks include hypotonia, obesity, short extremities, and delayed development. This syndrome has been described in patients with 1p, 2p, 3p, 6q, and 9q chromosome abnormalities and in cases with maternal uniparental disomy of chromosome 14 and fragile X syndrome.Case presentation: In the present report, we describe a 9-year-old Colombian patient who demonstrated features of PWS and was ultimately diagnosed with PWLS after genetic analysis revealed a 14.97 Mb deletion of 6q16.1–q21.Conclusions: This is the first reported case of PWLS in Colombia and represents one of the largest documented 6q21 deletions.

  2. Cushing syndrome

    Science.gov (United States)

    Hypercortisolism; Cortisol excess; Glucocorticoid excess - Cushing syndrome ... The most common cause of Cushing syndrome is taking too much ... Cushing syndrome . Prednisone, dexamethasone, and prednisolone ...

  3. LEOPARD syndrome

    Science.gov (United States)

    Multiple lentigines syndrome; Noonan syndrome with multiple lentigines ... Genetics Home Reference -- ghr.nlm.nih.gov/condition/noonan-syndrome-with-multiple-lentigines National Organization for Rare Disorders -- ...

  4. Measurement of locus copy number by hybridisation with amplifiable probes.

    Science.gov (United States)

    Armour, J A; Sismani, C; Patsalis, P C; Cross, G

    2000-01-15

    Despite its fundamental importance in genome analysis, it is only recently that systematic approaches have been developed to assess copy number at specific genetic loci, or to examine genomic DNA for submicro-scopic deletions of unknown location. In this report we show that short probes can be recovered and amplified quantitatively following hybridisation to genomic DNA. This simple observation forms the basis of a new approach to determining locus copy number in complex genomes. The power and specificity of multiplex amplifiable probe hybridisation is demonstrated by the simultaneous assessment of copy number at a set of 40 human loci, including detection of deletions causing Duchenne muscular dystrophy and Prader-Willi/Angelman syndromes. Assembly of other probe sets will allow novel, technically simple approaches to a wide variety of genetic analyses, including the potential for extension to high resolution genome-wide screens for deletions and amplifications.

  5. Severe Hypoglycemia due to Isolated ACTH Deficiency in Children: A New Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Michael Y. Torchinsky

    2011-01-01

    Full Text Available Isolated ACTH deficiency causes life-threatening severe hypoglycemia. A 7-year-old girl with hypoglycemia due to this rare disorder is described. Our patient had undetectable plasma ACTH repeatedly and cortisol 0 mcg/dl before and after ACTH 1-24 stimulation. There was no evidence of other pituitary hormone deficiency. Glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose. Previously published data on isolated ACTH deficiency in children is summarized. Review of the literature showed that the prevalence of this condition could be underestimated in the neonatal period and in Prader-Willi syndrome. Isolated ACTH deficiency occurs in older children as well as in neonates.

  6. Slipped Capital Femoral Epiphysis as a Complication of Growth Hormone Therapy

    Directory of Open Access Journals (Sweden)

    Shuo-Yu Wang

    2007-01-01

    Full Text Available Slipped capital femoral epiphysis (SCFE is a rare complication of growth hormone (GH therapy. Here, we report three patients who developed SCFE during GH therapy. The first two patients had hypopituitarism and had started GH therapy at the age of 15 years 6 months and 13 years 9 months, respectively. SCFE developed 4 years and 1 year after GH therapy, respectively. The third patient had Prader-Willi syndrome with obesity and hypogonadism and began GH therapy at the age of 12 years and 11 months. SCFE developed 2 months after starting GH therapy. Pain over the hip joints or over the knees is an early sign of SCFE. Despite recommendation, none of the three patients continued GH therapy. A high index of suspicion during GH therapy in patients at high risk of SCFE is important for early diagnosis and appropriate management. [J Formos Med Assoc 2007;106(2 Suppl:S46-S50

  7. Fanconi syndrome

    Science.gov (United States)

    De Toni-Fanconi syndrome ... Fanconi syndrome can be caused by faulty genes, or it may result later in life due to kidney damage. Sometimes the cause of Fanconi syndrome is unknown. Common causes of Fanconi syndrome in ...

  8. Duane Syndrome

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Duane Syndrome En Español Read in Chinese What is Duane Syndrome? Duane syndrome, also called Duane retraction syndrome (DRS), ...

  9. Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay.

    Science.gov (United States)

    Burnside, Rachel D; Pasion, Romela; Mikhail, Fady M; Carroll, Andrew J; Robin, Nathaniel H; Youngs, Erin L; Gadi, Inder K; Keitges, Elizabeth; Jaswaney, Vikram L; Papenhausen, Peter R; Potluri, Venkateswara R; Risheg, Hiba; Rush, Brooke; Smith, Janice L; Schwartz, Stuart; Tepperberg, James H; Butler, Merlin G

    2011-10-01

    The proximal long arm of chromosome 15 has segmental duplications located at breakpoints BP1-BP5 that mediate the generation of NAHR-related microdeletions and microduplications. The classical Prader-Willi/Angelman syndrome deletion is flanked by either of the proximal BP1 or BP2 breakpoints and the distal BP3 breakpoint. The larger Type I deletions are flanked by BP1 and BP3 in both Prader-Willi and Angelman syndrome subjects. Those with this deletion are reported to have a more severe phenotype than individuals with either Type II deletions (BP2-BP3) or uniparental disomy 15. The BP1-BP2 region spans approximately 500 kb and contains four evolutionarily conserved genes that are not imprinted. Reports of mutations or disturbed expression of these genes appear to impact behavioral and neurological function in affected individuals. Recently, reports of deletions and duplications flanked by BP1 and BP2 suggest an association with speech and motor delays, behavioral problems, seizures, and autism. We present a large cohort of subjects with copy number alteration of BP1 to BP2 with common phenotypic features. These include autism, developmental delay, motor and language delays, and behavioral problems, which were present in both cytogenetic groups. Parental studies demonstrated phenotypically normal carriers in several instances, and mildly affected carriers in others, complicating phenotypic association and/or causality. Possible explanations for these results include reduced penetrance, altered gene dosage on a particular genetic background, or a susceptibility region as reported for other areas of the genome implicated in autism and behavior disturbances.

  10. Apo-ghrelin receptor (apo-GHSR1a Regulates Dopamine Signaling in the Brain

    Directory of Open Access Journals (Sweden)

    Andras eKern

    2014-08-01

    Full Text Available The orexigenic peptide hormone ghrelin is synthesized in the stomach and its receptor growth hormone secretagogue receptor (GHSR1a is expressed mainly in the central nervous system (CNS. In this review we confine our discussion to the physiological role of GHSR1a in the brain. Paradoxically, despite broad expression of GHSR1a in the CNS, other than trace amounts in the hypothalamus, ghrelin is undetectable in the brain. In our efforts to elucidate the function of the ligand-free ghrelin receptor (apo-GHSR1a we identified subsets of neurons that co-express GHSR1a and dopamine receptors. In this review we focus on interactions between apo-GHSR1a and dopamine-2 receptor (DRD2 and formation of GHSR1a:DRD2 heteromers in hypothalamic neurons that regulate appetite, and discuss implications for the treatment of Prader-Willi syndrome. GHSR1a antagonists of distinct chemical structures, a quinazolinone and a triazole, respectively enhance and inhibit dopamine signaling through GHSR1a:DRD2 heteromers by an allosteric mechanism. This finding illustrates a potential strategy for designing the next generation of drugs for treating eating disorders as well as psychiatric disorders caused by abnormal dopamine signaling. Treatment with a GHSR1a antagonist that enhances dopamine/DRD2 activity in GHSR1a:DRD2 expressing hypothalamic neurons has the potential to inhibit the uncontrollable hyperphagia associated with Prader-Willi syndrome. DRD2 antagonists are prescribed for treating schizophrenia, but these block dopamine signaling in all DRD2 expressing neurons and are associated with adverse side effects, including enhanced appetite and excessive weight gain. A GHSR1a antagonist of structural class that allosterically blocks dopamine/DRD2 action in GHSR1a:DRD2 expressing neurons would have no effect on neurons expressing DRD2 alone; therefore, the side effects of DRD2 antagonists would potentially be reduced thereby enhancing patient compliance.

  11. Hamartomatous polyposis syndromes

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus

    2014-01-01

    Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as ......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes...

  12. Which neurodevelopmental disorders get researched and why?

    Directory of Open Access Journals (Sweden)

    Dorothy V M Bishop

    2010-11-01

    Full Text Available There are substantial differences in the amount of research concerned with different disorders. This paper considers why.Bibliographic searches were conducted to identify publications (1985-2009 concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived.The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe.Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.

  13. An unusual case of adolescent type 2 diabetes mellitus: Prader–Willi syndrome

    Science.gov (United States)

    Basheer, Riyas; Jalal, Muhammed Jasim Abdul; Gomez, Ramesh

    2016-01-01

    Prader–Willi syndrome (PWS) is a complex genetic disorder, characterized by neonatal hypotonia, developmental delay, short stature, childhood obesity, hypogonadism, and characteristic facial features. Here we report a 21-year-old male who presented with uncontrolled glycemic status. He was diagnosed to have diabetes mellitus at the age of 15 with osmotic symptoms – polyuria, polydipsia, and polyphagia. In the early period, after diagnosis, his blood sugars were reasonably controlled with oral hypoglycemic agents. However, a year back, he was switched onto insulin therapy due to secondary OHA failure. On examination, his body mass index was 36 kg/m2. He had bilateral gynecomastia, decreased biparietal diameter, almond shaped eyes with esotropia. He had hypogonadism and also had mild cognitive impairment. He did not have any proximal myopathy or other focal neurological deficits. Hormonal evaluation showed low testosterone and inappropriately normal fluorescence in situ hybridization suggestive of central hypogonadism. With fetal and neonatal hypotonia, delayed developmental milestones, hypogonadism, and early onset diabetes, he fulfilled the clinical criteria for the diagnosis of PWS. Multidisciplinary approach of clinicians together with family and social support are essential to bring out the optimal outcome for such syndromic cases. PMID:27453871

  14. Unbiased ascertainment of a patient with a 47,XY, +pseudic (15)t(15;15)(q13;q13) karyotype by amniocentesis

    Energy Technology Data Exchange (ETDEWEB)

    Spector, E.; Prochazka, G.; Hamilton, S. [Univ. of Colorado School of Medicine, Denver (United States)] [and others

    1994-09-01

    A 47,XY,+mar male karyotype was found in all metaphases on an amniocentesis from a 36-year-old woman (G1,P0). The marker was G group size. Chromosome studies on the parents were normal. C-banding, NOR staining and FISH demonstrated that the marker was dicentric, bisatellited, derived from No. 15 and contained 2 copies of the chromosomal region flanked by the Prader-Willi/Angelman A and B probes. The final karyotype was: 47,XY,+pseudic(15)t(15;15)(q13;q13), making the fetus tetrasomic for the genes in the duplicated region. DNA marker studies for No. 15 (performed in the laboratory of Dr. David Ledbetter) revealed that the fetus had inherited on No. 15 from each parent and that the marker was derived from both maternal No. 15 chromosomes. The parents chose to continue the pregnancy. The baby was born at 38 weeks gestation, was mildly edematous and had Apgar scores of 4, 7, and 8 at 1, 5, and 10 min, respectively. The marker was confirmed to be present in placenta and the baby`s blood. Examination at 6 weeks showed appropriate growth and development. Data from published cases predict that this baby will be mentally retarded and may have seizures because he is tetrasomic for 15pter-q13, but will not have Prader-Willi or Angelman syndromes since he has biparental inheritance of his normal No. 15s. However, the published cases may represent a biased sample as most were identified in mentally retarded individuals, not by prenatal diagnosis. This infant`s development will continue to be followed closely.

  15. Construction of a DNA library representing 15q11-13 by subtraction of two flow sorted marker chromosome-specific libraries

    Energy Technology Data Exchange (ETDEWEB)

    Blennow, E.; Werelius, B.; Nordenskjoeld, M. [Karolinska Hospital, Stockholm (Sweden)] [and others

    1994-09-01

    Constitutional extra {open_quotes}marker chromosomes{close_quotes} are found in {approx}0.5/1000 of newborns. Of these, 50% are inverted duplications of the pericentromeric region of chromosome 15, including two variants; (1) inv dup(15)(pter{yields}q11:q11{yields}pter) and (2) inv dup(15) (pter{yields}q12-13::q12-13{yields}pter). Variant (1) is found in phenotypically normal individuals, whereas variant (2) will produce a typical clinical picture including mental retardation, autism, hyperactivity and discrete dysmorphic features. Fluorescence in situ hybridization (FISH) using single copy probes from the Prader-Willi region confirms these observations as well as chromosome painting using a flow-sorted marker chromosome-specific library from a variant (1) marker, hybridized to the chromosomes of a patient with a variant (2) marker chromosome. Followingly, a flow-sorted biotinylated variant (1) library was subtracted from a non-labeled variant (2) library using magnetic beads and subsequent amplification by degenerate oligonucleotide-primed PCR (DOP-PCR). The successful result was demonstrated by using the amplified material for chromosome painting on chromosome slides from variant (1) and variant (2) patients. We have constructed a library from 15q11-13. This region contains genes producing a specific abnormal phenotype when found in a tri- or tetrasomic state. The region also contains the genes responsible for the Prader-Willi and Angelman syndromes when the paternal/maternal copy is missing, respectively. It is therefore a region where parental imprinting plays an important role. The isolated library may be used to isolate single copy clones which will allow further investigations of this region.

  16. Complex chromosome rearrangements related 15q14 microdeletion plays a relevant role in phenotype expression and delineates a novel recurrent syndrome

    Directory of Open Access Journals (Sweden)

    Tomaiuolo Anna

    2011-04-01

    Full Text Available Abstract Complex chromosome rearrangements are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. These are rarely seen in the general population but their frequency should be much higher due to balanced states with no phenotypic presentation. These abnormalities preferentially occur de novo during spermatogenesis and are transmitted in families through oogenesis. Here, we report a de novo complex chromosome rearrangement that interests eight chromosomes in eighteen-year-old boy with an abnormal phenotype consisting in moderate developmental delay, cleft palate, and facial dysmorphisms. Standard G-banding revealed four apparently balanced traslocations involving the chromosomes 1;13, 3;19, 9;15 and 14;18 that appeared to be reciprocal. Array-based comparative genomic hybridization analysis showed no imbalances at all the breakpoints observed except for an interstitial microdeletion on chromosome 15. This deletion is 1.6 Mb in size and is located at chromosome band 15q14, distal to the Prader-Willi/Angelman region. Comparing the features of our patient with published reports of patients with 15q14 deletion this finding corresponds to the smallest genomic region of overlap. The deleted segment at 15q14 was investigated for gene content.

  17. Marfan Syndrome

    Science.gov (United States)

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood vessels, ... A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, and ...

  18. Aarskog syndrome

    Science.gov (United States)

    Aarskog disease; Aarskog-Scott syndrome; AAS; Faciodigitogenital syndrome; Gaciogenital dysplasia ... Aarskog syndrome is a genetic disorder that is linked to the X chromosome. It affects mainly males, but females ...

  19. Williams syndrome

    Science.gov (United States)

    Williams-Beuren syndrome ... Williams syndrome is caused by not having a copy of several genes. It may be passed down in families. ... history of the condition. However, people with Williams syndrome have a 50% chance of passing the disorder ...

  20. Cushing's Syndrome

    OpenAIRE

    宗, 友厚; 伊藤, 勇; 諏訪, 哲也; 武田, 純; MUNE, Tomoatsu

    2003-01-01

    Sixteen cases of verified Cushing's syndrome, and twelve cases of probable Cushing's syndrome were reviewed and data on them were compared with various reports on Cushing's syndrome in the literature.

  1. Tourette syndrome

    Science.gov (United States)

    Gilles de la Tourette syndrome; Tic disorders - Tourette syndrome ... Tourette syndrome is named for Georges Gilles de la Tourette, who first described this disorder in 1885. The disorder is likely passed down through families. ...

  2. Hepatorenal syndrome

    Science.gov (United States)

    ... 2016:chap 153. Nevah MI, Fallon MB. Hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and other systemic complications of liver disease. In: Feldman M, Friedman LS, Brandt LJ, ...

  3. Cushing's Syndrome

    Science.gov (United States)

    Cushing's syndrome is a hormonal disorder. The cause is long-term exposure to too much cortisol, a hormone that ... your body to make too much cortisol. Cushing's syndrome is rare. Some symptoms are Upper body obesity ...

  4. Usher Syndrome

    Science.gov (United States)

    Usher syndrome is an inherited disease that causes serious hearing loss and retinitis pigmentosa, an eye disorder that causes ... and vision. There are three types of Usher syndrome: People with type I are deaf from birth ...

  5. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  6. Reye Syndrome

    Science.gov (United States)

    Reye syndrome is a rare illness that can affect the blood, liver, and brain of someone who has recently ... a viral illness, seek medical attention immediately. Reye syndrome can lead to a coma and brain death, ...

  7. Rett Syndrome

    Science.gov (United States)

    Rett syndrome is a rare genetic disease that causes developmental and nervous system problems, mostly in girls. It's related to autism spectrum disorder. Babies with Rett syndrome seem to grow and develop normally at first. ...

  8. Caplan syndrome

    Science.gov (United States)

    ... enable JavaScript. Rheumatoid pneumoconiosis (RP; also known as Caplan syndrome) is swelling (inflammation) and scarring of the ... avoid exposure to inorganic dust. Alternative Names RP; Caplan syndrome; Pneumoconiosis - rheumatoid; Silicosis - rheumatoid pneumoconiosis; Coal worker's ...

  9. Turner Syndrome

    Science.gov (United States)

    Turner syndrome is a genetic disorder that affects a girl's development. The cause is a missing or incomplete ... t work properly. Other physical features typical of Turner syndrome are Short, "webbed" neck with folds of skin ...

  10. Gardner's syndrome

    International Nuclear Information System (INIS)

    Sobrado Junior, C.W.; Bresser, A.; Cerri, G.G.; Habr-Gama, A.; Pinotti, H.W.; Magalhaes, A.

    1988-01-01

    A case of familiar poliposis of colon related to a right mandibular osteoma is reported (this association is usually called Gardner's syndrome). Radiologic pictures ae shown and some commentaries about this syndrome concerning the treatment are made. (author) [pt

  11. Sotos Syndrome

    Science.gov (United States)

    ... Clinical Trials Organizations Publications Definition Sotos syndrome (cerebral gigantism) is a rare genetic disorder caused by mutation ... have also been reported. × Definition Sotos syndrome (cerebral gigantism) is a rare genetic disorder caused by mutation ...

  12. Felty syndrome

    Science.gov (United States)

    Seropositive rheumatoid arthritis (RA); Felty's syndrome ... The cause of Felty syndrome is unknown. It is more common in people who have had rheumatoid arthritis (RA) for a long time. People with ...

  13. Bartter syndrome

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000308.htm Bartter syndrome To use the sharing features on this page, please enable JavaScript. Bartter syndrome is a group of rare conditions that affect ...

  14. Pendred Syndrome

    Science.gov (United States)

    ... other possible long-term consequences of the syndrome. Children with Pendred syndrome should start early treatment to gain communication skills, such as learning sign language or cued speech or learning to ...

  15. Dravet Syndrome

    Science.gov (United States)

    ... and supports a broad program of basic and clinical research on all types of epilepsy, including Dravet syndrome. Study of the genetic defects responsible for Dravet syndrome and related ... Publications Definition Dravet ...

  16. Down Syndrome

    Science.gov (United States)

    ... Down syndrome increases as a woman gets older. Down syndrome cannot be cured. Early treatment programs can help improve skills. They may include ... occupational, and/or educational therapy. With support and treatment, many ... Down syndrome live happy, productive lives. NIH: National Institute of ...

  17. Rowell syndrome

    Directory of Open Access Journals (Sweden)

    Ramesh Y Bhat

    2014-01-01

    Full Text Available Rowell syndrome is a rare disease consisting of erythema multiforme-like lesions associated with lupus erythematosus. The syndrome occurs mostly in middle-aged women. The authors describe the syndrome in a 15-year-old boy who responded well to systemic steroids and hydroxychloroquine.

  18. Aicardi Syndrome

    Science.gov (United States)

    ... from Aicardi-Goutieres syndrome, which is an inherited encephalopathy that affects newborn infants.) × Definition Aicardi syndrome is a rare genetic ... from Aicardi-Goutieres syndrome, which is an inherited encephalopathy that affects newborn infants.) View Full Definition Treatment There is no ...

  19. Dravets syndrom

    DEFF Research Database (Denmark)

    Hansen, Lars Kjaersgård; Rasmussen, Niels Henrik; Ousager, Lilian Bomme

    2010-01-01

    Dravet syndrome is an epileptic syndrome of infancy and early childhood. Most cases of Dravet syndrome seem to be due to a genetic defect causing the sodium channel to malfunction. We describe the main features of the syndrome. This epilepsy is medically intractable, but we call attention...... to the fact that some medications are of benefit and some could exacerbate the condition. Early recognition of the syndrome including by genetic testing could possibly improve outcome and reduce the need for other specialized investigations. Udgivelsesdato: 2010-Feb-22...

  20. Urofacial syndrome

    Directory of Open Access Journals (Sweden)

    Kamal F Akl

    2012-01-01

    Full Text Available The urofacial syndrome is characterized by functional obstructive uropathy asso-ciated with an inverted smile. The importance of the subject is that it sheds light, not only on the muscles of facial expression, but also on the inheritance of voiding disorders and lower urinary tract malformations. We report a 10-year-old-male patient who had the urofacial syndrome. Early diagnosis of the urofacial syndrome is important to avoid upper urinary tract damage and renal failure.

  1. Refeeding syndrome

    OpenAIRE

    Tripathy, Swagata; Mishra, Padmini; Dash, S. C.

    2008-01-01

    Refeeding syndrome is a potentially fatal medical condition that may affect malnourished patients in response to an inappropriately rapid overfeeding. This commonly occurs following the institution of nutritional support, especially parenteral or enteral nutrition. The most characteristic pathophysiology of refeeding syndrome relates to the rapid consumption of phosphate after glucose intake and subsequent hypophosphatemia. Refeeding syndrome can manifest as either metabolic changes (hypokala...

  2. Revesz syndrome

    Directory of Open Access Journals (Sweden)

    Dayane Cristine Issaho

    2015-04-01

    Full Text Available Revesz syndrome is a rare variant of dyskeratosis congenita and is characterized by bilateral exudative retinopathy, alterations in the anterior ocular segment, intrauterine growth retardation, fine sparse hair, reticulate skin pigmentation, bone marrow failure, cerebral calcification, cerebellar hypoplasia and psychomotor retardation. Few patients with this syndrome have been reported, and significant clinical variations exist among patients. This report describes the first Brazilian case of Revesz syndrome and its ocular and clinical features.

  3. Reye's Syndrome

    Science.gov (United States)

    ... that contain aspirin. Some hospitals and medical facilities conduct newborn screenings for fatty acid oxidation disorders to determine which children are at greater risk of developing Reye's syndrome. ...

  4. Marfan Syndrome (For Teens)

    Science.gov (United States)

    ... genetic disorder called Marfan syndrome. What Is Marfan Syndrome? Marfan syndrome is named after Antoine Marfan, the French ... immediately. What's Life Like for Teens With Marfan Syndrome? Marfan syndrome affects people differently, so life is not ...

  5. Learning about Marfan Syndrome

    Science.gov (United States)

    ... Additional Resources for Marfan Syndrome What is Marfan syndrome? Marfan syndrome is one of the most common inherited ... FAQ Top of page Additional Resources For Marfan Syndrome Marfan syndrome [nlm.nih.gov] From Medline Plus Marfan ...

  6. Russell-Silver syndrome

    Science.gov (United States)

    Silver-Russell syndrome; Silver syndrome; RSS; Russell-Silver syndrome ... One in 10 children with this syndrome has a problem involving chromosome 7. In other people with the syndrome, it may affect chromosome 11. Most of the time, it ...

  7. What Is Usher Syndrome?

    Science.gov (United States)

    ... Action You are here Home › Retinal Diseases Listen Usher Syndrome What is Usher syndrome? How is Usher syndrome ... available? Are there any related diseases? What is Usher Syndrome? Usher syndrome is an inherited condition characterized by ...

  8. Seckel syndrome: an overdiagnosed syndrome.

    OpenAIRE

    Thompson, E; Pembrey, M

    1985-01-01

    Five children in whom a diagnosis of Seckel syndrome had previously been made were re-examined in the genetic unit. One child had classical Seckel syndrome, a sib pair had the features of the syndrome with less severe short stature, and in two children the diagnosis was not confirmed. Seckel syndrome is only one of a group of low birth weight microcephalic dwarfism and careful attention should be paid to fulfillment of the major criteria defined by Seckel before the diagnosis is made. There r...

  9. Burnout Syndrome

    OpenAIRE

    Panova, Gordana; Panov, Nenad; Stojanov, H; Sumanov, Gorgi; Panova, Blagica; Stojanovski, Angel; Nikolovska, Lence; Jovevska, Svetlana; Trajanovski, D; Asanova, D

    2013-01-01

    Introduction: Increasing work responsibilities, allocation of duties, loss of energy and motivation in everyday activities, emotional exhaustion, lack of time for themselves, insuffi cient time for rest and recreation, dissatisfaction in private life. All these symptoms can be cause of Burnout Syndrome. Aim: To see the importance of this syndrome, the consequences of job dissatisfaction, the environment, family and expression in drastic chan...

  10. Tourette Syndrome

    Science.gov (United States)

    If you have Tourette syndrome, you make unusual movements or sounds, called tics. You have little or no control over them. Common tics are throat- ... spin, or, rarely, blurt out swear words. Tourette syndrome is a disorder of the nervous system. It ...

  11. Fahr's Syndrome

    Science.gov (United States)

    ... or 50s, although it can occur at any time in childhood or adolescence. × Definition Fahr's Syndrome is a rare, genetically dominant, inherited ... or 50s, although it can occur at any time in childhood or adolescence. View Full Definition Treatment There is no cure for Fahr's Syndrome, ...

  12. Lemierre's syndrome

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Bødtger, Uffe; Heltberg, Ole

    2014-01-01

    Lemierre's syndrome is an often un-diagnosed disease seen in previously healthy young subjects, presenting with symptoms of pharyngitis, fever and elevated markers of inflammation. The syndrome is characterised by infectious thrombosis of the jugular vein due to infection with Fusobacteria, causing...

  13. Ambras syndrome

    Directory of Open Access Journals (Sweden)

    Sudhir Malwade

    2015-01-01

    Full Text Available Ambras syndrome, a form of congenital hypertrichosis lanuginosa, is extremely rare in neonates. It is characterized by typical pattern of hair distribution, dysmorphic facial features and a familial pattern of inheritance. We report a case of Ambras syndrome in a preterm neonate with history of consanguinity and positive family history.

  14. Antiphospholipid syndrome

    DEFF Research Database (Denmark)

    Cervera, Ricard; Piette, Jean-Charles; Font, Josep

    2002-01-01

    To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression.......To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression....

  15. Noonan syndrome

    OpenAIRE

    Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

    2013-01-01

    Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid ris...

  16. TAFRO Syndrome.

    Science.gov (United States)

    Igawa, Takuro; Sato, Yasuharu

    2018-02-01

    TAFRO syndrome is a newly recognized variant of idiopathic multicentric Castleman disease (iMCD) that involves a constellation of syndromes: thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Thrombocytopenia and severe anasarca accompanied by relatively low serum immunoglobulin levels are characteristic clinical findings of TAFRO syndrome that are not present in iMCD-not otherwise specified (iMCD-NOS). Lymph node biopsy is recommended to exclude other diseases and to diagnose TAFRO syndrome, which reveals characteristic histopathological findings similar to hyaline vascular-type CD. TAFRO syndrome follows a more aggressive course, compared with iMCD-NOS, and there is no standard treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Goldenhar syndrome

    Directory of Open Access Journals (Sweden)

    Neeraj Sharma

    2013-01-01

    Full Text Available Goldenhar syndrome is a syndrome of complex structures developing from first and second branchial arches during blastogenesis. The etiology of this rare disease is not fully understood, as it has shown itself variable genetically and of unclear causes. The disorder is characterized by a wide spectrum of symptoms and physical features that may vary greatly in range and severity from case to case. Here we present a unique case of Goldenhar syndrome with absence of left condyle, hypoplasia of the zygomatic bone, no pneumatization of the mastoid process, underdeveloped mandible, bifid tongue and the skin tags in the preauricular area.

  18. Cowden syndrome

    Directory of Open Access Journals (Sweden)

    Ravi Prakash S

    2010-01-01

    Full Text Available Cowden syndrome or multiple hamartoma syndrome is an autosomal dominant condition with variable expressions that result mainly from mutation in the PTEN gene on arm 10q. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal tract, bones, CNS, eyes, and genitourinary tract. Mucocutaneous features include trichilemmomas, oral mucosal papillomatosis, acral keratosis, and palmoplantar keratosis. Here we present a case of Cowden syndrome in a 14-year-old female patient with the chief complaint of multiple oral papillomatous lesions.

  19. Costello syndrome

    Directory of Open Access Journals (Sweden)

    Madhukara J

    2007-01-01

    Full Text Available Costello syndrome is a rare, distinctive, multiple congenital anomaly syndrome, characterized by soft, loose skin with deep palmar and plantar creases, loose joints, distinctive coarse facial features and skeletal and cardiac abnormalities. The affected patients have a predisposition to develop malignancy, developmental delays and mental retardation. Recently, a 7-year-old male child born to normal nonconsanguineous parents presented to us with abnormal facial features, arrhythmia, mitral valve dysfunction and growth retardation. His cutaneous examination revealed lax and pigmented skin over hands and feet with deep creases, acanthosis nigricans and short curly hairs. Its differentiation from other syndromes with similar clinical features is discussed in this article.

  20. Reye Syndrome

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now What Is Reye’s Syndrome? ...

  1. Alagille Syndrome

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Alagille Syndrome Back Alagille ...

  2. Turner Syndrome

    Science.gov (United States)

    ... Failure to begin sexual changes expected during puberty Sexual development that "stalls" during teenage years Early end to menstrual cycles not due to pregnancy For most women with Turner syndrome, inability to ...

  3. [Refeeding syndrome].

    Science.gov (United States)

    Ševela, Stanislav; Novák, František; Kazda, Antonín; Brodská, Helena

    Despite being known more than 60 years, refeeding syndrome (RS) still bears many uncertainties. For example, its definition is not clear and definite, and the attitude to it varies from the complete neglect to over-prevention.The term "refeeding syndrome" refers to electrolyte and metabolic changes occurring in malnourished patients after the readministration of nutrition. These changes concern especially to phosphates and ions. Potassium, magnesium, naturism and fluids balance are involved. The changes lead to cell energetic metabolism and electric potential disturbances, with related clinical symptoms.Fully developed refeeding syndrome is quite rare; nevertheless it can be fatal for the patient. However, even its development can lead to many complications increasing the patient's morbidity and the length of stay in the hospital. Yet the refeeding syndrome is more or less predictable and if kept in mind also preventable.The aim of this article is to get the reader to know more about this metabolic phenomenon and possible attitudes towards it.

  4. Cockayne syndrome

    DEFF Research Database (Denmark)

    Karikkineth, Ajoy C; Scheibye-Knudsen, Morten; Fivenson, Elayne

    2017-01-01

    Cockayne syndrome (CS) is a disorder characterized by a variety of clinical features including cachectic dwarfism, severe neurological manifestations including microcephaly and cognitive deficits, pigmentary retinopathy, cataracts, sensorineural deafness, and ambulatory and feeding difficulties...

  5. Alagille Syndrome

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  6. Reye Syndrome

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  7. Turner Syndrome

    Science.gov (United States)

    ... crowding, and osteoporosis (brittle bones). Because of their physical conditions, health concerns, and infertility, some girls and women with TS may have low self- esteem, anxiety, or depression. How is Turner syndrome diagnosed? Physical features may ...

  8. Cushing's Syndrome

    Science.gov (United States)

    ... person cured of Cushing’s syndrome might have some memory loss and slight mental decline. But the change is ... Categories: Family Health, Infants and Toddlers, Kids and Teens, Men, Seniors, WomenTags: acth, adenomas, hormone, sickness September ...

  9. Levator Syndrome

    Science.gov (United States)

    ... Abscess Anorectal Fistula Foreign Objects in the Rectum Hemorrhoids Levator Syndrome Pilonidal Disease Proctitis Rectal Prolapse (See ... out other painful rectal conditions (such as thrombosed hemorrhoids , fissures , or abscesses ). The physical examination is often ...

  10. Alport Syndrome

    Science.gov (United States)

    ... signs and symptoms may differ, based on age, gender and inherited type of Alport syndrome. For example, ... prevention and treatment of kidney disease. The Better Business Bureau Wise Giving Alliance Charity Seal provides the ...

  11. Gilbert's Syndrome

    Science.gov (United States)

    ... not know you have the condition until it's discovered by accident, such as when a blood test ... chemotherapy drug Some protease inhibitors used to treat HIV If you have Gilbert's syndrome, talk to your ...

  12. Potter syndrome

    Science.gov (United States)

    Potter phenotype ... In Potter syndrome, the primary problem is kidney failure. The kidneys fail to develop properly as the baby is ... kidneys normally produce the amniotic fluid (as urine). Potter phenotype refers to a typical facial appearance that ...

  13. Moebius Syndrome

    Science.gov (United States)

    ... delays; high or cleft palate; hearing problems and speech difficulties. Children with Moebius syndrome are unable to move their eyes back and forth. Decreased numbers of muscle fibers have been reported. Deformities of the tongue, jaw, and limbs, such ...

  14. Fraser syndrome

    DEFF Research Database (Denmark)

    Barisic, Ingeborg; Odak, Ljubica; Loane, Maria

    2013-01-01

    Fraser syndrome is a rare autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, laryngeal, and urogenital malformations. We present a population-based epidemiological study using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network of...

  15. Angelman Syndrome

    Science.gov (United States)

    ... therapy for seizures is usually necessary. Physical and occupational therapies, communication therapy, and behavioral therapies are important in allowing individuals with Angelman syndrome to reach their maximum developmental potential. × Treatment There ...

  16. Joubert Syndrome

    Science.gov (United States)

    ... CEP290 . View Full Definition Treatment Treatment for Joubert syndrome is symptomatic and supportive. Infant stimulation and physical, occupational, and speech therapy may benefit some children. Infants with abnormal breathing ...

  17. Zellweger Syndrome

    Science.gov (United States)

    ... swallow. Some babies will be born with glaucoma, retinal degeneration, and impaired hearing. Jaundice and gastrointestinal bleeding also may occur. Treatment There is no cure for Zellweger syndrome, nor ...

  18. Nephrotic Syndrome

    Science.gov (United States)

    ... your blood — typically with an artificial kidney machine (dialyzer). Chronic kidney disease. Nephrotic syndrome may cause your ... opportunities Reprint Permissions A single copy of these materials may be reprinted for noncommercial personal use only. " ...

  19. Ohtahara Syndrome

    Science.gov (United States)

    ... are more often affected than girls. View Full Definition Treatment Antiepileptic drugs are used to control seizures, but are unfortunately ... Other therapies are symptomatic and supportive. × ... Definition Ohtahara syndrome is a neurological disorder characterized by ...

  20. Usher Syndrome

    Science.gov (United States)

    ... to abnormal development of the vestibular hair cells, sensory cells that detect gravity and head movement. RP ... 3 Ben-Rebeh, I., et al. (2016). Genetic analysis of Tunisian families with Usher syndrome type 1: ...

  1. Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

    Directory of Open Access Journals (Sweden)

    Grabe Hans

    2010-06-01

    Full Text Available Abstract Background Obsessive-compulsive disorder (OCD is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome, suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients. Methods We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA. Results No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients. Conclusions Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.

  2. Obesity in Childhood and Adolescence, Genetic Factors.

    Science.gov (United States)

    Kostovski, Marko; Tasic, Velibor; Laban, Nevena; Polenakovic, Momir; Danilovski, Dragan; Gucev, Zoran

    2017-12-01

    Obesity and excess weight are a pandemic phenomenon in the modern world. Childhood and adolescent obesity often ends up in obesity in adults. The costs of obesity and its consequences are staggering for any society, crippling for countries in development. Childhood obesity is also widespread in Macedonia. Metabolic syndrome, dyslipidemia and carbohydrate intolerance are found in significant numbers. Parents and grandparents are often obese. Some of the children are either dysmorphic, or slightly retarded. We have already described patients with Prader-Willi syndrome, Bardet-Biedl syndrome or WAGR syndrome. A genetic screening for mutations in monogenic obesity in children with early, rapid-onset or severe obesity, severe hyperphagia, hypogonadism, intestinal dysfunction, hypopigmentation of hair and skin, postprandial hypoglycaemia, diabetes insipidus, abnormal leptin level and coexistence of lean and obese siblings in the family discovers many genetic forms of obesity. There are about 30 monogenic forms of obesity. In addition, obesity is different in ethnic groups, and the types of monogenic obesity differ. In brief, an increasing number of genes and genetic mechanisms in children continue to be discovered. This sheds new light on the molecular mechanisms of obesity and potentially gives a target for new forms of treatment.

  3. Eagle's Syndrome

    OpenAIRE

    Pinheiro,Thaís Gonçalves; Soares,Vítor Yamashiro Rocha; Ferreira,Denise Bastos Lage; Raymundo,Igor Teixeira; Nascimento,Luiz Augusto; Oliveira,Carlos Augusto Costa Pires de

    2013-01-01

    Summary Introduction:?Eagle's syndrome is characterized by cervicopharyngeal signs and symptoms associated with elongation of the styloid apophysis. This elongation may occur through ossification of the stylohyoid ligament, or through growth of the apophysis due to osteogenesis triggered by a factor such as trauma. Elongation of the styloid apophysis may give rise to intense facial pain, headache, dysphagia, otalgia, buzzing sensations, and trismus. Precise diagnosis of the syndrome is diffic...

  4. Barth Syndrome

    DEFF Research Database (Denmark)

    Saric, Ana; Andreau, Karine; Armand, Anne-Sophie

    2016-01-01

    Mutations in the gene encoding the enzyme tafazzin, TAZ, cause Barth syndrome (BTHS). Individuals with this X-linked multisystem disorder present cardiomyopathy (CM) (often dilated), skeletal muscle weakness, neutropenia, growth retardation, and 3-methylglutaconic aciduria. Biopsies of the heart......, liver and skeletal muscle of patients have revealed mitochondrial malformations and dysfunctions. It is the purpose of this review to summarize recent results of studies on various animal or cell models of Barth syndrome, which have characterized biochemically the strong cellular defects associated...

  5. Pendred's syndrome

    International Nuclear Information System (INIS)

    Hashmi, M.I.; Cheema, I.A.; Qasim, G.

    2003-01-01

    This report describes Pendred's syndrome in three siblings of a consanguineous marriage, belonging to Rahimyar Khan. The children presented with deafmutism and goiters. The investigations included scintigram, perchlorate discharge test and audiometery. The perchlorate discharge was positive in index case. Bilateral sensorineural hearing defect was detected on Pure Tone Average (PTA) audiometry. Meticulous clinical and laboratory evaluation is mandatory for the detection of rare disorders like Pendred's syndrome. (author)

  6. [Poland's syndrome].

    Science.gov (United States)

    Slezak, R; Sasiadek, M

    2000-08-01

    Poland's syndrome consists of the variable clinical features, but always includes unilateral aplasia of the chest wall muscles and ipsilateral anomalies of upper extremity. The incidence of Poland's syndrome, reported by different authors ranges from 1:10,000 to 1:100,000 and is observed more frequently in males than in females with the right side of the body affected more often than the left. The etiology of this syndrome is still discussed. However most of described cases were sporadic, rare familial incidence of Poland's syndrome were also presented. Therefore different etiologic factors of the Poland's syndrome are taken into account: genetic, vascular compromise during early stages of embriogenesis but also teratogenic effect of environmental xenobiotics (e.g. cigarette smoking by pregnant women). The authors present also the case of 20-years old man with inherited bilateral syndactyly with the right side aplasia of major pectoralis muscle and face asymmetry. The familial history was negative in respect to the features, associated with Poland's syndrome.

  7. What is Metabolic Syndrome?

    Science.gov (United States)

    ... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

  8. Loeys-Dietz Syndrome

    Science.gov (United States)

    ... to the signs and symptoms of Loeys-Dietz syndrome. Marfan syndrome is different from Loeys-Dietz syndrome in that the gene mutation which causes Marfan syndrome is in fibrillin-1 (FBN-1), a protein ...

  9. Milk-alkali syndrome

    Science.gov (United States)

    Calcium-alkali syndrome; Cope syndrome; Burnett syndrome; Hypercalcemia; Calcium metabolism disorder ... Milk-alkali syndrome is almost always caused by taking too many calcium supplements, usually in the form of calcium carbonate. Calcium ...

  10. Exogenous Cushing syndrome

    Science.gov (United States)

    Cushing syndrome - corticosteroid induced; Corticosteroid-induced Cushing syndrome; Iatrogenic Cushing syndrome ... Cushing syndrome is a disorder that occurs when your body has a higher than normal level of the hormone ...

  11. Turner Syndrome: Other FAQs

    Science.gov (United States)

    ... Other FAQs Share Facebook Twitter Pinterest Email Print Turner Syndrome: Other FAQs Basic information for topics, such as " ... been diagnosed with Turner syndrome. Now what? Is Turner syndrome inherited? Turner syndrome is usually not inherited, but ...

  12. Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort.

    Science.gov (United States)

    Feinberg, Jason I; Bakulski, Kelly M; Jaffe, Andrew E; Tryggvadottir, Rakel; Brown, Shannon C; Goldman, Lynn R; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Fallin, M Daniele; Feinberg, Andrew P

    2015-08-01

    Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features. Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children. We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (∼485 000 CpG sites). We also examined associated regions in an independent sample of post-mortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available. Using region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)] Autism Observational Scale for Infants (AOSI) at 12 months of age in offspring. The DMRs clustered near genes involved in developmental processes, including many genes in the SNORD family, within the Prader-Willi syndrome gene cluster. These results were consistent among the 75 probes on the Illumina 450K array that cover AOSI-associated DMRs from CHARM. Further, 18 of 75 (24%) 450K array probes showed consistent differences in the cerebellums of autistic individuals compared with controls. These data suggest that epigenetic differences in paternal sperm may contribute to autism risk in

  13. Pfeiffer syndrome

    Directory of Open Access Journals (Sweden)

    Fryns Jean-Pierre

    2006-06-01

    Full Text Available Abstract Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on hands and feet. Hydrocephaly may be found occasionally, along with severe ocular proptosis, ankylosed elbows, abnormal viscera, and slow development. Based on the severity of the phenotype, Pfeiffer syndrome is divided into three clinical subtypes. Type 1 "classic" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur. Pfeiffer syndrome affects about 1 in 100,000 individuals. The disorder can be caused by mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. Pfeiffer syndrome can be diagnosed prenatally by sonography showing craniosynostosis, hypertelorism with proptosis, and broad thumb, or molecularly if it concerns a recurrence and the causative mutation was found. Molecular genetic testing is important to confirm the diagnosis. Management includes multiple-staged surgery of craniosynostosis. Midfacial surgery is performed to reduce the exophthalmos and the midfacial hypoplasia.

  14. Molecular approaches to child psychopathology.

    Science.gov (United States)

    Alsobrook, J P; Pauls, D L

    1998-04-01

    Basic research into the genetics of childhood psychiatric disorders has substantially increased during the last two decades. Specific genetic mutations have been characterized in some developmental disorders (e.g., fragile X syndrome and Prader-Willi syndrome), but thus far identification of etiological gene mutations in psychiatric illnesses has been unsuccessful. Several psychiatric disorders serve as examples of the current state of molecular approaches in child psychopathology. Investigations to date of Gilles de la Tourette's syndrome (GTS) have not resulted in the discovery of a gene of major effect. Some studies have implicated the D2 and D4 dopamine receptors as having a direct role in the etiology of GTS, but other studies have disputed those findings. However, the dopamine D2 receptor may modulate the severity of GTS. Obsessive-compulsive disorder has a reported association with a low-activity allele of the enzyme catechol-O-methyltransferase; however, the low-activity genotype is also seen in a significant proportion of unaffected individuals. For reading disability two distinct phenotypes (phonological awareness and single-word reading) have been linked to separate loci on chromosomes 6 and 15. Attention deficit hyperactivity disorder (ADHD) has a reported association with the dopamine transporter. Findings of a genetic locus for the personality trait of novelty seeking remain controversial.

  15. Are mice pigmentary genes throwing light on humans?

    Directory of Open Access Journals (Sweden)

    Bose S

    1993-01-01

    Full Text Available In this article the rapid advances made in the molecular genetics of inherited disorders of hypo and hyperpigmentation during the past three years are reviewed. The main focus is on studies in mice as compared to homologues in humans. The main hypomelanotic diseases included are, piebaldism (white spotting due to mutations of c-KIT, PDGF and MGF genes; vitiligo (microphathalmia mice mutations of c-Kit and c-fms genes; Waardenburg syndrome (splotch locus mutations of mice PAX-3 or human Hup-2 genes; albinism (mutations of tyrosinase genes, Menkes disease (Mottled mouse, premature graying (mutations in light/brown locus/gp75/ TRP-1; Griscelli disease (mutations in TRP-1 and steel; Prader-willi and Angelman syndromes, tyrosinase-positive oculocutaneous albinism and hypomelanosis of lto (mutations of pink-eyed dilution gene/mapping to human chromosomes 15 q 11.2 - q12; and human platelet storage pool deficiency diseases due to defects in pallidin, an erythrocyte membrane protein (pallid mouse / mapping to 4.2 pallidin gene. The genetic characterization of hypermelanosis includes, neurofibromatosis 1 (Café-au-lait spots and McCune-Albright Syndrome. Rapid evolving knowledge about pigmentary genes will increase further the knowledge about these hypo and hyperpigmentary disorders.

  16. Nevoid basal cell carcinoma syndrome

    Science.gov (United States)

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic ... syndrome is known as PTCH ("patched"). The gene is passed down ...

  17. Water Fluoridation Statistics - Percent of PWS population receiving fluoridated water

    Data.gov (United States)

    U.S. Department of Health & Human Services — 2000-2014. Water Fluoridation Statistics is a biennial report of the percentage and number of people receiving fluoridated water from 2000 through 2014, originally...

  18. PWS_Dashboard_2.png | ECHO | US EPA

    Science.gov (United States)

    ECHO, Enforcement and Compliance History Online, provides compliance and enforcement information for approximately 800,000 EPA-regulated facilities nationwide. ECHO includes permit, inspection, violation, enforcement action, and penalty information about facilities regulated under the Clean Air Act (CAA) Stationary Source Program, Clean Water Act (CWA) National Pollutant Elimination Discharge System (NPDES), and/or Resource Conservation and Recovery Act (RCRA). Information also is provided on surrounding demographics when available.

  19. PWS_Dashboard_1.png | ECHO | US EPA

    Science.gov (United States)

    ECHO, Enforcement and Compliance History Online, provides compliance and enforcement information for approximately 800,000 EPA-regulated facilities nationwide. ECHO includes permit, inspection, violation, enforcement action, and penalty information about facilities regulated under the Clean Air Act (CAA) Stationary Source Program, Clean Water Act (CWA) National Pollutant Elimination Discharge System (NPDES), and/or Resource Conservation and Recovery Act (RCRA). Information also is provided on surrounding demographics when available.

  20. A nowcast-forecast information system for PWS

    International Nuclear Information System (INIS)

    Thomas, G.L.; Cox, W.

    2000-01-01

    The development of the Prince William Sound Oil Spill Recovery Institute's (ORI) nowcast-forecast information system was discussed. OSRI addresses oil spill response and prevention research and development in the Arctic and subArctic. A realistic electronic model of the ecosystem was a much needed tool for efficient prioritization of oil spill technologies. The OSRI Sound Ecosystem Assessment (SEA) research program focused on developing a physical-biological model that consisted of static and biological resources that change over long time periods. This includes bathymetry, shoreline type, and substrate-dependent vegetation. It also focused on developing a model of dynamic properties such as wind, weather, plankton, and wildlife populations that undergo significant changes on annual or shorter time scales. The nowcast information system is a long-term development project which uses the Princeton ocean model (POM), a static runoff model, a network of weather and water observation stations, an Intranet which allows the observational data to run in near-real time and an Internet home page. It will contribute to sustaining the natural resources of coastal areas. It was concluded that the nowcast-forecast information system has short-term applications to oil spill prevention and response and long-term applications to the natural resources at risk to spills. 33 refs