-
Advances in Pediatrics Aug 2022Growth hormone (GH) is an injectable medication originally used to replace the deficiency of the hormone, but has expanded to treating conditions that may reduce growth... (Review)
Review
Growth hormone (GH) is an injectable medication originally used to replace the deficiency of the hormone, but has expanded to treating conditions that may reduce growth and adult height even when the body maintains endogenous GH production. In the United States, there are 8 Food and Drug Administration (FDA)-approved indications for pediatric GH therapy: GH deficiency, Prader-Willi Syndrome, small for gestational age (SGA) without catch-up growth, idiopathic short stature, Turner syndrome, SHOX gene haploinsufficiency, Noonan Syndrome, and chronic renal insufficiency. We characterize the growth patterns and effects of GH treatment in each of these indications. We also review patterns of growth that warrant referral to a pediatric endocrinologist, as well as safety updates. This review is intended to guide practitioners on the initial evaluation and management of patients with short stature, and the indications for GH therapy.
Topics: Adult; Child; Dwarfism; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; Prader-Willi Syndrome; Turner Syndrome; United States
PubMed: 35985710
DOI: 10.1016/j.yapd.2022.03.005 -
Genes Sep 2021This Special Issue includes 15 peer-reviewed articles for publication by experts in Prader-Willi syndrome (PWS) and their reflective area of interest impacting this rare...
This Special Issue includes 15 peer-reviewed articles for publication by experts in Prader-Willi syndrome (PWS) and their reflective area of interest impacting this rare disorder [...].
Topics: Databases, Genetic; Genetic Association Studies; Humans; Pharmacogenomic Testing; Phenotype; Prader-Willi Syndrome; Rare Diseases
PubMed: 34573411
DOI: 10.3390/genes12091429 -
Nature Reviews. Disease Primers Apr 2022Hypothalamic syndrome (HS) is a rare disorder caused by disease-related and/or treatment-related injury to the hypothalamus, most commonly associated with rare,... (Review)
Review
Hypothalamic syndrome (HS) is a rare disorder caused by disease-related and/or treatment-related injury to the hypothalamus, most commonly associated with rare, non-cancerous parasellar masses, such as craniopharyngiomas, germ cell tumours, gliomas, cysts of Rathke's pouch and Langerhans cell histiocytosis, as well as with genetic neurodevelopmental syndromes, such as Prader-Willi syndrome and septo-optic dysplasia. HS is characterized by intractable weight gain associated with severe morbid obesity, multiple endocrine abnormalities and memory impairment, attention deficit and reduced impulse control as well as increased risk of cardiovascular and metabolic disorders. Currently, there is no cure for this condition but treatments for general obesity are often used in patients with HS, including surgery, medication and counselling. However, these are mostly ineffective and no medications that are specifically approved for the treatment of HS are available. Specific challenges in HS are because the syndrome represents an adverse effect of different diseases, and that diagnostic criteria, aetiology, pathogenesis and management of HS are not completely defined.
Topics: Craniopharyngioma; Endocrine System Diseases; Humans; Hypothalamus; Pituitary Neoplasms; Prader-Willi Syndrome
PubMed: 35449162
DOI: 10.1038/s41572-022-00351-z -
International Journal of Molecular... Feb 2023Prader-Willi syndrome (PWS) is a complex genetic disorder with three PWS molecular genetic classes and presents as severe hypotonia, failure to thrive,... (Review)
Review
Prader-Willi syndrome (PWS) is a complex genetic disorder with three PWS molecular genetic classes and presents as severe hypotonia, failure to thrive, hypogonadism/hypogenitalism and developmental delay during infancy. Hyperphagia, obesity, learning and behavioral problems, short stature with growth and other hormone deficiencies are identified during childhood. Those with the larger 15q11-q13 Type I deletion with the absence of four non-imprinted genes () from the 15q11.2 BP1-BP2 region are more severely affected compared with those with PWS having a smaller Type II deletion. and genes encode magnesium and cation transporters, supporting brain and muscle development and function, glucose and insulin metabolism and neurobehavioral outcomes. Lower magnesium levels are reported in those with Type I deletions. The gene encodes a protein associated with fragile X syndrome. The gene is associated with attention-deficit hyperactivity disorder (ADHD) and compulsions, more commonly seen in PWS with the Type I deletion. When the 15q11.2 BP1-BP2 region alone is deleted, neurodevelopment, motor, learning and behavioral problems including seizures, ADHD, obsessive-compulsive disorder (OCD) and autism may occur with other clinical findings recognized as Burnside-Butler syndrome. The genes in the 15q11.2 BP1-BP2 region may contribute to more clinical involvement and comorbidities in those with PWS and Type I deletions.
Topics: Humans; Carrier Proteins; Chromosomes; Chromosomes, Human, Pair 15; Magnesium; Prader-Willi Syndrome
PubMed: 36901699
DOI: 10.3390/ijms24054271 -
Nutrients May 2022Prader-Willi syndrome (PWS) is a complex genetic disorder which involves the endocrine and neurologic systems, metabolism, and behavior. The aim of this paper is to... (Review)
Review
Prader-Willi syndrome (PWS) is a complex genetic disorder which involves the endocrine and neurologic systems, metabolism, and behavior. The aim of this paper is to summarize current knowledge on dietary management and treatment of PWS and, in particular, to prevent excessive weight gain. Growth hormone (GH) therapy is the recommended standard treatment for PWS children, because it improves body composition (by changing the proportion of body fat and lean body mass specifically by increasing muscle mass and energy expenditure), linear growth, and in infants, it promotes psychomotor and IQ development. In early childhood, the predominant symptom is hyperphagia which can lead to early onset, severe obesity with different obesity-related comorbidities. There are several studies on anti-obesity medications (metformin, topiramate, liraglutide, setmelanotide). However, these are still limited, and no widely accepted consensus guideline exists concerning these drugs in children with PWS. Until there is a specific treatment for hyperphagia and weight gain, weight must be controlled with the help of diet and exercise. Below the age of one year, children with PWS have no desire to eat and will often fail to thrive, despite adequate calories. After the age of two years, weight begins to increase without a change in calorie intake. Appetite increases later, gradually, and becomes insatiable. Managing the progression of different nutritional phases (0-4) is really important and can delay the early onset of severe obesity. Multidisciplinary approaches are crucial in the diagnosis and lifelong follow-up, which will determine the quality of life of these patients.
Topics: Child; Child, Preschool; Humans; Hyperphagia; Infant; Obesity, Morbid; Prader-Willi Syndrome; Quality of Life; Weight Gain
PubMed: 35565916
DOI: 10.3390/nu14091950 -
Journal of Endocrinological... Oct 2021Prader-Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. The three main... (Review)
Review
Prader-Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. The three main genetic subtypes are represented by paternal 15q11-q13 deletion, maternal uniparental disomy 15, and imprinting defect. Clinical picture of PWS changes across life stages. The main clinical characteristics are represented by short stature, developmental delay, cognitive disability and behavioral diseases. Hypotonia and poor suck resulting in failure to thrive are typical of infancy. As the subjects with PWS age, clinical manifestations such as hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency due to hypothalamic dysfunction occur. Obesity and its complications are the most common causes of morbidity and mortality in PWS. Several mechanisms for the aetiology of obesity in PWS have been hypothesized, which include aberration in hypothalamic pathways of satiety control resulting in hyperphagia, disruption in hormones regulating appetite and satiety and reduced energy expenditure. However, despite the advancement in the research field of the genetic basis of obesity in PWS, there are contradictory data on the management. Although it is mandatory to adopt obesity strategy prevention from infancy, there is promising evidence regarding the management of obesity in adulthood with current obesity drugs along with lifestyle interventions, although the data are limited. Therefore, the current manuscript provides a review of the current evidence on obesity and PWS, covering physiopathological aspects, obesity-related complications and conservative management.
Topics: Animals; Humans; Obesity; Phenotype; Prader-Willi Syndrome
PubMed: 33891302
DOI: 10.1007/s40618-021-01574-9 -
The Lancet. Diabetes & Endocrinology Apr 2021Prader-Willi syndrome is a rare genetic neurodevelopmental disorder resulting from the loss of expression of maternally imprinted genes located in the paternal... (Review)
Review
Prader-Willi syndrome is a rare genetic neurodevelopmental disorder resulting from the loss of expression of maternally imprinted genes located in the paternal chromosomal region, 15q11-13. Impaired hypothalamic development and function is the cause of most of the phenotypes comprising the developmental trajectory of Prader-Willi syndrome: from anorexia at birth to excessive weight gain preceding hyperphagia, and early severe obesity with hormonal deficiencies, behavioural problems, and dysautonomia. Growth hormone deficiency, hypogonadism, hypothyroidism, premature adrenarche, corticotropin deficiency, precocious puberty, and glucose metabolism disorders are the main endocrine dysfunctions observed. Additionally, as a result of hypothalamic dysfunction, oxytocin and ghrelin systems are impaired in most patients. Standard pituitary and gonadal hormone replacement therapies are required. In this Review, we discuss Prader-Willi syndrome as a model of hypothalamic dysfunction, and provide a comprehensive description of the accumulated knowledge on genetics, pathophysiology, and treatment approaches of this rare disorder.
Topics: Animals; Endocrine System Diseases; Humans; Hypothalamus; Prader-Willi Syndrome; Proteins
PubMed: 33647242
DOI: 10.1016/S2213-8587(21)00002-4 -
International Journal of Molecular... Jan 2023Prader-Willi syndrome (PWS) is a complex, genetic, neurodevelopmental disorder. PWS has three molecular genetic classes. The most common defect is due to a paternal... (Review)
Review
Prader-Willi syndrome (PWS) is a complex, genetic, neurodevelopmental disorder. PWS has three molecular genetic classes. The most common defect is due to a paternal 15q11-q13 deletion observed in about 60% of individuals. This is followed by maternal disomy 15 (both 15 s from the mother), found in approximately 35% of cases. the remaining individuals have a defect of the imprinting center that controls the activity of imprinted genes on chromosome 15. Mild cognitive impairment and behavior problems in PWS include self-injury, anxiety, compulsions, and outbursts in childhood, impacted by genetic subtypes. Food seeking and hyperphagia can lead to morbid obesity and contribute to diabetes and cardiovascular or orthopedic problems. The control of hyperphagia and improving food-related behaviors are the most important unmet needs in PWS and could be addressed with the development of a new therapeutic agent, as currently no approved therapeutics exist for PWS treatment. The status of clinical trials with existing results for the management of obesity and hyperphagia in PWS will be discussed in this review, including treatments such as beloranib, setmelanotide, a diazoxide choline controlled-release tablet (DCCR), an unacylated ghrelin analogue, oxytocin and related compounds, glucagon-like peptide 1 receptor agonists, surgical intervention, and transcranial direct-current stimulation.
Topics: Female; Humans; Prader-Willi Syndrome; Transcranial Direct Current Stimulation; Hyperphagia; Anxiety; Mothers
PubMed: 36768472
DOI: 10.3390/ijms24032150 -
The Journal of Clinical Endocrinology... Dec 2022Prader-Willi syndrome (PWS) is characterized by lack of appetite control and hyperphagia, leading to obesity. Pharmacological options for weight management are needed. (Randomized Controlled Trial)
Randomized Controlled Trial
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.
METHODS
This was a multicenter, 52-week, placebo-controlled trial with a 16-week double-blinded period. Adolescents (n = 31, aged 12-17 years; Tanner stage 2-5) and children (n = 24, aged 6-11 years; Tanner stage <2) with PWS and obesity were included. Patients were randomized 2:1 to liraglutide 3.0 mg (or maximum-tolerated dose) or placebo for 16 weeks, after which placebo was stopped. Liraglutide was continued for 52 weeks. All patients followed a structured diet and exercise program throughout the trial. The coprimary endpoints were change in body mass index (BMI) standard deviation score (SDS) from baseline to 16 and 52 weeks. Secondary endpoints included other weight-related parameters, hyperphagia, and safety.
RESULTS
Change in BMI SDS from baseline to weeks 16 and 52 was not significantly different between treatments in adolescents (estimated treatment difference: -0.07 at week 16 and -0.14 at week 52) and children (-0.06 and -0.07, respectively). Changes in other weight-related parameters between treatments were not significant. At week 52, hyperphagia total and drive scores were lower in adolescents treated with liraglutide vs no treatment. The most common adverse events with liraglutide were gastrointestinal disorders.
CONCLUSION
Although the coprimary endpoints were not met, changes in hyperphagia total and drive scores in adolescents warrant further studies on liraglutide in this population.
Topics: Child; Adolescent; Humans; Liraglutide; Prader-Willi Syndrome; Obesity; Hyperphagia; Body Mass Index
PubMed: 36181471
DOI: 10.1210/clinem/dgac549 -
The Journal of Clinical Endocrinology... May 2022Prader-Willi syndrome (PWS) is a rare, multisystemic, genetic disorder involving the hypothalamus. It is caused by loss of expression of paternally inherited genes in...
Prader-Willi syndrome (PWS) is a rare, multisystemic, genetic disorder involving the hypothalamus. It is caused by loss of expression of paternally inherited genes in chromosome 15 q11-13 region. The estimated incidence is around 1 in 20.000 births. PWS is characterized by a complex lifelong trajectory involving neurodevelopmental, nutritional, endocrine, metabolic, and behavioral changes. The major symptoms are hypotonia, short stature, hypogonadism, and eating disorders ranging from anorexia in infancy to hyperphagia, a deficit of satiety, and a high risk of severe obesity. The patients display intellectual disability comprising cognitive deficit, delayed motor and language development, learning deficits, impaired social skills, and emotional regulation. Behavioral features including temper outbursts, anxiety, obsessive-compulsive symptoms and rigidity are common and become more apparent with increasing age. Almost all have hypogonadism and growth hormone deficiency. Central adrenal insufficiency is rare whereas central hypothyroidism occurs in up to 30% of children with PWS. The prevalence of obesity increases with age from almost none in early childhood to more than 90% in adulthood. Up to 25% of adults with obesity have type 2 diabetes. Obesity and its complications are the major causes of comorbidity and mortality in PWS. As there is no specific treatment, care consists of comprehensive management of feeding disorders, a restricted, controlled diet, regular exercise, hormone substitution, and screening and treatment of comorbidities. Here we present the course of PWS from birth to adulthood in 2 patients and discuss their symptoms in relation to the literature.
Topics: Adult; Child; Child, Preschool; Diabetes Mellitus, Type 2; Humans; Hyperphagia; Hypogonadism; Obesity; Prader-Willi Syndrome
PubMed: 35150573
DOI: 10.1210/clinem/dgac082