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Neonatal presentation of Prader Willi syndrome. Personal records
Abstract
Prader Willi Syndrome (PWS) is characterized by typical appearance, obesity, short stature, hypothalamic hypogonadism, cryptorchidism, hypotonia, behavioural abnormalities and mental retardation. It is considered as a continuous genes syndrome with different genotypes: microdeletion of the region 15q11-q13 with paternal imprinting; maternal uniparental disomy (UPD) of chromosome 15; chromosomal rearrangement. Clinical manifestations evolve with age from newborn (hypotonia, poor sucking, hypoplastic external genitalia) to childhood (delay in psychomotor development, hyperphagia, obesity, acromicria and craniofacial dysmorphisms). We present five newborns who received an early diagnosis, based on clinical presentation. The early treatment and follow-up can in fact improve the natural evolution of the syndrome in order to prevent respiratory tract diseases and obesity, and to improve growth.
... Behavioral challenges vary across age and PWS subtype. In infancy, there are more physical than behavioral concerns, including hypotonia, feeding difficulties, failure to thrive, hypogonadism, lethargy, and decreased interest in feeding [11,12]. Early childhood often brings a significant increase in both externalizing (tantrums, aggression, stealing, etc.) and internalizing (anxiety and depression, skin picking, etc.) behaviors [10,13]. ...
This study sought to describe food- and non-food-related behaviors of children aged 3 to 18 years with Prader-Willi syndrome (PWS) in home and school settings, as assessed by 86 parents and 63 teachers using 7 subscales of the Global Assessment of Individual's Behavior (GAIB). General Behavior Problem, Non-Food-Related Behavior Problem, and Non-Food-Related Obsessive Speech and Compulsive Behavior (OS/CB) scores did not differ significantly between parent and teacher reports. Food-Related Behavior Problem scores were higher in parent versus teacher reports when the mother had less than a college education (difference of 13.6 points, 95% Confidence Interval (CI) 5.1 to 22). Parents assigned higher Food-Related OS/CB scores than teachers (difference of 5.7 points, 95% CI 2.4 to 9.0). Although teachers reported fewer Food-Related OS/CB, they scored overall OS/CB higher for interfering with daily activities compared with parents (difference of 0.9 points, 95% CI 0.4 to 1.4). Understanding how behaviors manifest in home and school settings, and how they vary with socio-demographic and patient characteristics can help inform strategies to reduce behavior problems and improve outcomes.
... First described in 1956 by Prader, Labhart, and Willi, Prader–Willi syndrome (PWS) is a complex neurodevelopmental disorder that affects approximately 1 in 20,000 births with no distinguishing sex, race, or social status association.1 Individuals with PWS are typically short, obese, possess small hands and feet, and have dysmorphic features such as a narrow bifrontal diameter, full cheeks, and almond shaped eyes.2 In the neonatal period, diminished fetal activity, hypotonia, and feeding difficulty persist followed by hyperphagia, delayed psychomotor development, early onset obesity, incomplete sexual development in adolescence, sleep apnea, intellectual disabilities, and a behavioral profile that includes obsessive, compulsive, oppositional, and defiant behaviors.3 Individuals with PWS typically have intellectual disabilities (borderline to mild/moderate mental retardation) and exhibit a higher overall behavior disturbance compared to individuals with intellectual disability of unknown etiology.4 ...
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.
Résumé
Le syndrome de Prader-Willi (SPW) est une maladie génétique d’empreinte aboutissant à l’absence d’expression des gènes de la région du chromosome 15q11.q13 d’origine paternelle. Sa prévalence est estimée entre 1/10 000 à 1/25 000 naissances. Il se manifeste initialement par une hypotonie néonatale associée à des troubles de l’oralité et un hypogonadisme. Dans un second temps, on observe un retard de développement, des troubles du comportement avec hyperphagie et obésité importante. Le diagnostic, évoqué sur des critères cliniques, est confirmé par les analyses génétiques. Il est possible en anténatal, évoqué devant un hydramnios avec fœtus petit pour l’âge gestationnel, immobilisme fœtal et malposition des doigts. Nous rapportons une série de 5 nouveau-nés présentant un SPW. L’objectif principal était d’étudier les signes d’appel anténatals et périnatals du SPW. La prévalence dans notre population est de 1/7937 naissances. Le SPW avait été évoqué sur des critères cliniques : hypotonie sévère, troubles de l’oralité, dysmorphie et anomalies des organes génitaux. Quatre enfants étaient nés à terme avec un poids de naissance proche du 10e percentile pour 2 enfants, inférieur au 3e percentile pour 2 avec un périmètre crânien normal. Quatre enfants présentaient une malposition des doigts. Les analyses génétiques avaient montré une délétion sur le chromosome 15 paternel pour 3 enfants, une unidisomie maternelle pour 2 enfants. Le SPW doit être recherché devant une hypotonie néonatale sévère, ce d’autant que s’y associent dysmorphie, hypogonadisme, malposition des doigts et histoire anténatale évocatrice. Le diagnostic précoce, voire anténatal, permet une meilleure prise en charge pluridisciplinaire de l’enfant et de sa famille.
A case of three months age baby with Prader-Willi syndrome (PWS) is presented, the case was related to with an interstitial deletion of the 15 chromosome: 46 XY, deletion 15 (q11-q13). The seven points of the criteria of Holm's were satisfied for the diagnosis, and an early detection will allow a better prognostic.
A 29-week premature infant with severe central hypoventilation secondary to Prader-Willi syndrome required mechanical ventilation until 55 days of age. This disorder must be considered in the differential diagnosis of a premature infant who does not have primary lung disease but has significant hypotonia because the respiratory failure may require prolonged supportive care.
Considering cost as a factor, the authors evaluated three approaches to the diagnostic testing of Prader-Willi syndrome (PWS) and Angelman syndrome (AS).
The approaches evaluated were (1) DNA methylation studies followed by fluorescence in situ hybridization (FISH) for any positive DNA result, (2) FISH analysis followed by DNA testing for any negative result, and (3) simultaneous DNA testing and FISH analysis.
Of 136 samples submitted for chromosome analysis and DNA methylation analysis for PWS or AS, 114 had a normal chromosome analysis and methylation studies, 9 were positive for AS, 3 were positive for PWS, and 7 had an abnormal chromosome analysis, but not deletion 15q11.2-q13, and normal methylation studies. On the basis of these results, the authors compared the cost of each testing strategy.
DNA methylation studies followed by confirmation with FISH for any positive result yields a significant cost savings compared with the other approaches.
During the neonatal period the diagnosis of the Prader-Willi syndrome (PWS) is difficult because the syndrome is expressed mainly by severe hypotonia at this age and the typical clinical features of later life are not yet present.
To identify all the PWS clinical markers in severe hypotonic newborns, which could facilitate an early diagnosis of the syndrome.
Twenty-one PWS newborns (14 males and 7 females) with severe hypotonia at birth were evaluated. Paediatricians skilled in syndromology carried out a careful clinical examination. Fluorescent in situ hybridization (FISH) analysis and/or a methylation test was used to confirm the PWS clinical diagnosis.
The clinical diagnosis of PWS was reached at a mean age of 7.4 mo with genetic confirmation at 11 mo of life. In 12 newborns at least 3 craniofacial features were present (57%), suggesting the diagnosis of PWS. Two craniofacial dysmorphic characteristics were described in 6 newborns and only 1 in 3 cases. Cryptorchidism was monolateral in 6 and bilateral in 7 patients; in one newborn both testes were in scrotum. A micropenis was described in one patient and hypoplasia of the labia minora was reported in two females.
Diagnosis by means of dysmorphologic evaluation is difficult in the neonatal period. The presence of severe hypotonia should always induce neonatologists to perform specific genetic tests in order to obtain an early diagnosis of PWS.