Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13. In infancy it is characterized by hypotonia with poor suck resulting in failure to thrive. As the child ages, other manifestations such as developmental delay, cognitive disability, and behavior problems become evident. Hypothalamic dysfunction has been implicated in many manifestations of this syndrome including hyperphagia, temperature instability, high pain threshold, sleep disordered breathing, and multiple endocrine abnormalities. These include growth hormone deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and complications of obesity such as type 2 diabetes mellitus. This review summarizes the recent literature investigating optimal screening and treatment of endocrine abnormalities associated with PWS, and provides an update on nutrition and food-related behavioral intervention. The standard of care regarding growth hormone therapy and surveillance for potential side effects, the potential for central adrenal insufficiency, evaluation for and treatment of hypogonadism in males and females, and the prevalence and screening recommendations for hypothyroidism and diabetes are covered in detail. PWS is a genetic syndrome in which early diagnosis and careful attention to detail regarding all the potential endocrine and behavioral manifestations can lead to a significant improvement in health and developmental outcomes. Thus, the important role of the provider caring for the child with PWS cannot be overstated.

ObjectiveGut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity.DesignWe performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression.Results333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed.ConclusionsAntibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

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.

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