Longitudinal Changes in Acylated versus Unacylated Ghrelin Levels May Be Involved in the Underlying Mechanisms of the Switch in Nutritional Phases in Prader-Willi Syndrome.

Introduction: Prader-Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. An elevated, more unfavorable ratio between acylated and unacylated ghrelin (AG/UAG ratio) might play a role in the underlying mechanisms of this switch. We aimed to assess the evolution of the appetite-regulating hormones acylated ghrelin (AG) and unacylated ghrelin (UAG) and the AG/UAG ratio and their association with the change in eating behavior in children with PWS, compared to healthy age-matched controls.

What underlies emotion regulation abilities? An innovative programme based on an integrative developmental approach to improve emotional competencies: Promising results in children with Prader-Willi syndrome.

Background: This study aimed to test the effect of a new training programme on emotional competencies, named EMO-T, and to show the value of an integrative developmental approach. This approach postulates that the emotion regulation disturbances commonly observed in neurodevelopmental disorders are the consequence of potential disruptions in the prerequisite emotion skills. This integrative approach is particularly suitable in the case of complex and multidimensional disorders such as Prader-Willi syndrome (PWS), a rare genetic disease.

First step towards a consensus strategy for multi-locus diagnostic testing of imprinting disorders.

Background: Imprinting disorders, which affect growth, development, metabolism and neoplasia risk, are caused by genetic or epigenetic changes to genes that are expressed from only one parental allele. Disease may result from changes in coding sequences, copy number changes, uniparental disomy or imprinting defects. Some imprinting disorders are clinically heterogeneous, some are associated with more than one imprinted locus, and some patients have alterations affecting multiple loci.

Liraglutide for Weight Management in Children and Adolescents With Prader-Willi Syndrome and Obesity.

Context: Prader-Willi syndrome (PWS) is characterized by lack of appetite control and hyperphagia, leading to obesity. Pharmacological options for weight management are needed.

Objective: To determine whether liraglutide treatment for weight management is superior to placebo/no treatment in pediatric individuals with PWS.

Impact of Deprivation on Obesity in Children with PWS.

Our study aimed to evaluate the social deprivation score in families with a child with Prader-Willi syndrome (PWS) and analyze its impact on the occurrence of obesity in the affected child. We included 147 children with PWS followed in our reference center with Evaluation of the Deprivation and Inequalities of Health in Healthcare Centres by the EPICES score. Deprivation (EPICES ≥ 30) was found in 25.

Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients.

Type 2 diabetes mellitus (T2DM) affects 20% of patients with Prader-Willi syndrome (PWS), with many cases diagnosed during the transition period. Our aim was to describe the natural history of T2DM in patients with PWS before the age of 25 years and to develop screening and preventive strategies. Thirty-nine patients followed in the French PWS Reference Center were included (median age 25.

Paradoxical low severity of COVID-19 in Prader-Willi syndrome: data from a French survey on 647 patients.

Background: Patients with Prader-Willi syndrome (PWS) often have comorbidities, especially obesity, that may constitute a risk factor for severe forms of COVID-19. We aimed to assess prevalence and medical course of SARS-CoV-2 infection in children and adults with PWS. From November 2020 to January 2021, we performed a detailed medical survey on 342 adults and 305 children with PWS followed in the French reference center.

Prader-Willi syndrome: Hormone therapies.

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder linked to the lack of expression of specific maternally imprinted genes located in the chromosomal region 15q11-q13. Impaired hypothalamic development and function explain most of the phenotype that is characterized by a specific trajectory from anorexia at birth to excessive weight gain at later ages, which is accompanied by hyperphagia and early severe obesity, as well as by other hormonal deficiencies, behavioral deficits, and dysautonomia. In almost all patients, their endocrine dysfunction involves growth hormone deficiency and hypogonadism, which originate from a combination of both peripheral and hypothalamic origin, central hypothyroidism in 40%, precocious adrenarche in 30% of the cases, and in rare cases, also adrenocorticotropin deficiency and precocious puberty.

SNORD116 and growth hormone therapy impact IGFBP7 in Prader-Willi syndrome.

Purpose: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with hypothalamic dysfunction due to deficiency of imprinted genes located on the 15q11-q13 chromosome. Among them, the SNORD116 gene appears critical for the expression of the PWS phenotype. We aimed to clarify the role of SNORD116 in cellular and animal models with regard to growth hormone therapy (GHT), the main approved treatment for PWS.

Equivocal expression of emotions in children with Prader-Willi syndrome: what are the consequences for emotional abilities and social adjustment?

Background: People with Prader-Willi Syndrome (PWS) experience great difficulties in social adaptation that could be explained by disturbances in emotional competencies. However, current knowledge about the emotional functioning of people with PWS is incomplete. In particular, despite being the foundation of social adaptation, their emotional expression abilities have never been investigated.

Causes of death in Prader-Willi syndrome: lessons from 11 years' experience of a national reference center.

Background: In the last 20 years, substantial improvements have been made in the diagnosis, treatment and management of patients with Prader-Willi syndrome (PWS). Few data on causes of death are available since those improvements were made. Our study assessed the causes of death among French patients with PWS over the first 11 years of experience of the nationwide French Reference Center for PWS (FRC-PWS).

Evolution of Hip Dysplasia in Pediatric Patients With Prader-Willi Syndrome Treated With Growth Hormone Early in Development.

Background: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by obesity, hypotonia, feeding difficulties, obesity, musculoskeletal manifestations including scoliosis, and hip dysplasia (HD). The aim of this study was to characterize the clinical and radiographic evolution of HD in the pediatric PWS population.

Methods: The authors performed a retrospective cohort study of 72 patients (147 anteroposterior pelvic radiographs) between January 2004 and December 2016.

Prader-Willi syndrome: A model for understanding the ghrelin system.

Subsequent to the discovery of ghrelin as the endogenous ligand of growth hormone secretagogue receptor 1a, this unique gut peptide has been found to exert numerous physiological effects, such as appetite stimulation and lipid accumulation via the central regulating mechanisms in the hypothalamus, stimulation of gastric motility, regulation of glucose metabolism and brown fat thermogenesis, and modulation of stress, anxiety, taste sensation, reward-seeking behaviour and the sleep/wake cycle. Prader-Willi syndrome (PWS) has been described as a unique pathological state characterised by severe obesity and high circulating levels of ghrelin. It was hypothesised that hyperghrelinaemia would explain at least a part of the feeding behaviour and body composition of PWS patients, who are characterised by hyperphagia, an obsession with food and food-seeking, and increased adiposity.

Growth Hormone Treatment for Prader-Willi Syndrome.

The European Marketing Authorization for recombinant human growth hormone (rhGH) in children with Prader-Willi syndrome was the first indication for metabolic and body composition effects in children. In the US it is indicated for short stature associated with PWS. Recombinant hGH is the first treatment for the PWS population and radically changed the care of these children by facilitating access to physicians who prescribe rhGH, mainly paediatric endocrinologists, and manage the organization of multidisciplinary care.

Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency.

Context Abnormalities in the hypothalamo-pituitary-gonadal axis have long been reported in Noonan syndrome (NS) males with only few data available in prepubertal children. Objective The aim of this study was to describe the gonadal function of NS males from childhood to adulthood. Design It is a retrospective chart review.

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial.

Context And Objective: Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available.

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

Background: 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.

Methods: Data were collected on 61 infants with a molecular diagnosis of PWS born in 2012 and 2013 in France.

Sequelae of GH Treatment in Children with PWS.

More than 15 years after rGH was granted marketing authorization for children with PWS, a review of the sequelae, side effects and safety issues of rGH therapy is timely. The publications on issues concerning respiratory function, glucose metabolism, fat mass, and scoliosis at baseline and with rGH treatment are herein presented. We discuss the impact of rGH side effects, make proposals to prevent or treat them, and emphasise the remaining questions and perspectives.

The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome.

Background And Objectives: Patients with Prader-Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS.

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

Background: 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.