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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 -
American Journal of Medical Genetics.... May 2022Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypotonia and poor feeding in infancy which progresses to hyperphagia in early-mid childhood, as well...
Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypotonia and poor feeding in infancy which progresses to hyperphagia in early-mid childhood, as well as developmental delays, a spectrum of behavioral and psychiatric concerns, endocrinopathies, orthopedic issues, and less commonly, seizures, sleep apnea, and narcolepsy with or without cataplexy. This study used data in the Global PWS Registry (N = 893) to explore the onset and severity over time of the neuropsychiatric features reported in individuals with PWS and explored its associations with sleep disorders, seizures, and psychiatric symptoms. Results demonstrate that seizures are more common in the deletion subtype and that narcolepsy and cataplexy are more common in individuals who have sleep-related seizures. Finally, this work shows that anxiety and compulsive behaviors are persistent features of PWS that may arise early in childhood, and that anxiety is associated with higher frequency of other comorbid psychiatric diagnoses. In conclusion, this study is one of the largest to date characterizing sleep disorders and neuropsychiatric characteristics of individuals with PWS and reports on the novel association between sleep disorders and seizures. This study is also one of the first to offer details on the nature of the progression of these features in individuals with PWS.
Topics: Anxiety Disorders; Cataplexy; Child; Humans; Narcolepsy; Prader-Willi Syndrome; Seizures
PubMed: 35098642
DOI: 10.1002/ajmg.a.62662 -
Bioscience Reports Jun 2022Prader-Willi Syndrome (PWS) is a rare complex genetic disease that is associated with pathological disorders that include endocrine disruption, developmental,... (Review)
Review
Prader-Willi Syndrome (PWS) is a rare complex genetic disease that is associated with pathological disorders that include endocrine disruption, developmental, neurological, and physical problems as well as intellectual, and behavioral dysfunction. In early stage, PWS is characterized by respiratory distress, hypotonia, and poor sucking ability, causing feeding concern and poor weight gain. Additional features of the disease evolve over time. These include hyperphagia, obesity, developmental, cognitive delay, skin picking, high pain threshold, short stature, growth hormone deficiency, hypogonadism, strabismus, scoliosis, joint laxity, or hip dysplasia. The disease is associated with a shortened life expectancy. There is no cure for PWS, although interventions are available for symptoms management. PWS is caused by genetic defects in chromosome 15q11.2-q13, and categorized into three groups, namely Paternal deletion, Maternal uniparental disomy, and Imprinting defect. PWS is confirmed through genetic testing and DNA-methylation analysis. Studies revealed that at least two key proteins namely MAGEL-2 and NECDIN along with two proteases PCSK1 and PCSK2 are linked to PWS. Herein, we summarize our current understanding and knowledge about the role of these proteins and enzymes in various biological processes associated with PWS. The review also describes how loss and/or impairment of functional activity of these macromolecules can lead to hormonal disbalance by promoting degradation of secretory granules and via inhibition of proteolytic maturation of precursor-proteins. The present review will draw attention of researchers, scientists, and academicians engaged in PWS study and will help to identify potential targets and molecular pathways for PWS intervention and treatment.
Topics: Endopeptidases; Genetic Testing; Humans; Obesity; Peptide Hydrolases; Prader-Willi Syndrome
PubMed: 35621394
DOI: 10.1042/BSR20220610 -
Pediatric Endocrinology, Diabetes, and... 2017Prader-Willi Syndrome is a genetic condition caused by an abnormality of chromosome 15, mostly resulting from a deletion.The prevalence of syndrome in Europe has been... (Review)
Review
Prader-Willi Syndrome is a genetic condition caused by an abnormality of chromosome 15, mostly resulting from a deletion.The prevalence of syndrome in Europe has been reported between 1 in 8,000 to 1 in 45,000 births. Characteristic features of the syndrome include hypotonia, short stature, psychomotor development delay, hypogonadism and progressive, life-threatening obesity. Treatment of Prader-Willi Syndrome consists of intensive rehabilitation, psychologicalcare, speech therapy and also, if patient is fulfilling appropriate criteria, growth hormone treatment. An extremely important element of therapy is also properly planned and implemented nutritional management. Adequate diet prevents the malnutrition in the first stage of life and the development of excessive weight in subsequent years. The aim of this article is to provide practical and accurate guidance on nutritional management and diet therapy for physicians and nutritionists who work with children, adolescents and adults with Prader-Willi Syndrome.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 15; Diet Therapy; Europe; Female; Humans; Infant; Male; Middle Aged; Practice Guidelines as Topic; Prader-Willi Syndrome; Prevalence; Young Adult
PubMed: 29073293
DOI: 10.18544/PEDM-23.02.0080 -
Journal of Clinical Sleep Medicine :... Jun 2022Clinical experience and a growing body of evidence suggest that sleep disturbances are common in people with Prader-Willi syndrome (PWS). PWS is a rare neuroendocrine... (Review)
Review
UNLABELLED
Clinical experience and a growing body of evidence suggest that sleep disturbances are common in people with Prader-Willi syndrome (PWS). PWS is a rare neuroendocrine disorder characterized by early hypotonia and feeding difficulties; developmental delays; endocrinopathies; and behavioral concerns, especially rigidity, anxiety, and behavioral outbursts. PWS is also characterized by decreased resting energy expenditure and transition to hyperphagia and obesity. We propose that, for many people with PWS, clinical diagnosis and management of sleep disorders is an unmet need. We present current information to suggest disordered sleep is a significant burden for individuals with PWS and often overlooked. While central and obstructive sleep apnea are more widely recognized in PWS, other sleep disorders have increasingly gained recognition, including hypersomnia, narcolepsy-like phenotypes, and insomnia. Sleep disorders can impact behavior, cognition, and quality of life and health for individuals with PWS. Our goal is to bring sleep disorders to the forefront of therapeutic intervention for patients with PWS. This paper presents a review of the literature and recommendations for clinical practice based on published research and our clinical experience as sleep specialists, geneticists, psychiatrists, pediatricians, otolaryngologists, and pulmonologists with extensive experience with this patient population. We recommend that management of sleep be considered an integral part of successful medical management of PWS. Further research concerning sleep problems in PWS is urgently needed to develop best practices and work toward a consensus statement for medical management to meet the needs of people with PWS.
CITATION
Duis J, Pullen LC, Picone M, et al. Diagnosis and management of sleep disorders in Prader-Willi syndrome. . 2022;18(6):1687-1696.
Topics: Disorders of Excessive Somnolence; Humans; Narcolepsy; Prader-Willi Syndrome; Quality of Life; Sleep Wake Disorders
PubMed: 35172921
DOI: 10.5664/jcsm.9938 -
Current Pediatric Reviews 2016Prader-Willi syndrome (PWS) is a neuro-developmental genetic disorder due to lack of expression of genes inherited from the paternal chromosome 15q11-q13 region with... (Review)
Review
BACKGROUND
Prader-Willi syndrome (PWS) is a neuro-developmental genetic disorder due to lack of expression of genes inherited from the paternal chromosome 15q11-q13 region with three main genetic subtypes. These include paternal 15q11-q13 deletion (about 70% of cases), maternal uniparental disomy 15 or both 15s from the mother (20-30% of cases), and defects in the imprinting center (1-3%) which controls the expression of imprinted genes in this chromosome region. Clinical manifestations include infantile hypotonia with a poor suck resulting in failure to thrive, short stature, small hands/feet and hypogonadism/hypogenitalism due to growth and other hormone deficiencies, hyperphagia and excessive weight gain with obesity and cognitive and behavioral problems including obsessive compulsions, tantrums and self-injury. The phenotype is likely related to hypothalamic dysfunction.
OBJECTIVE
Hyperphagia and obesity with related complications are major causes of morbidity and mortality in PWS requiring accurate diagnosis, appropriate medical management and treatment; the major objective of our report.
METHODS AND RESULTS
An extensive review of the literature was undertaken including genetics, clinical and behavioral aspects, and updated health-related information addressing the importance of early diagnosis and treatment of individuals with Prader-Willi syndrome. A searchable, bulleted and formatted list of topics related to this obesity syndrome was provided utilizing a Table of Contents approach for the clinical practitioner.
CONCLUSIONS
Physicians and other health care providers can use this review with clinical, genetic and treatment summaries divided into sections that are pertinent in the context of clinical practice. Finally, frequently asked questions by clinicians, families and other interested participants will be addressed.
Topics: Child; Child, Preschool; Cognition Disorders; Developmental Disabilities; Gene Expression Profiling; Genetic Counseling; Hormone Replacement Therapy; Humans; Hyperphagia; Obesity; Phenotype; Practice Guidelines as Topic; Prader-Willi Syndrome; Prognosis
PubMed: 26592417
DOI: 10.2174/1573396312666151123115250 -
Medecine Sciences : M/S Oct 2015Prader-Willi syndrome is a neurodevelopmental disorder caused by the lack of expression of imprinted genes of the chromosomal region 15q11-q12. Diagnosis can now be made... (Review)
Review
Prader-Willi syndrome is a neurodevelopmental disorder caused by the lack of expression of imprinted genes of the chromosomal region 15q11-q12. Diagnosis can now be made in the first months of life, allowing a precise description of the natural history of the disease. Of interest, nutritional phases appear to be more complex than those initially reported, starting with a severe hypotonia with deficit of suckling and failure to thrive in neonates, and subsequently switching to excessive weight gain with morbid obesity due to hyperphagia and deficit of satiety. The phenotype also includes endocrine dysfunction, intellectual disability, learning deficits, behavioural troubles with impaired social skills and psychiatric features. Multidisciplinary care has been strongly improved by the rare disease programme launched in France in 2004 and the Obesity programme in 2011 in link with the patient association. New therapeutic perspectives have arisen from knowledge of the pathophysiology of PWS.
Topics: Diagnosis, Differential; Disease Progression; France; Genetic Testing; Humans; Hypogonadism; Mental Disorders; Phenotype; Prader-Willi Syndrome
PubMed: 26481024
DOI: 10.1051/medsci/20153110011 -
Acta Paediatrica (Oslo, Norway : 1992).... Nov 1997Dysfunction of various hypothalamic systems may be the basis of a number of symptoms in Prader-Willi syndrome. The often abnormal position of the baby in the uterus at... (Review)
Review
Dysfunction of various hypothalamic systems may be the basis of a number of symptoms in Prader-Willi syndrome. The often abnormal position of the baby in the uterus at the onset of labour, the high percentage of infants with asphyxia and the high proportion of children born prematurely or post-maturely may all be related to abnormal fetal hypothalamic systems, as the fetal hypothalamus plays a crucial role in labour. Abnormal luteinizing hormone-releasing hormone neurones are thought to be responsible for the decreased levels of sex hormones, resulting in non-descended testes, undersized sex organs and insufficient growth during puberty. A lack of growth hormone-releasing hormone may also contribute to the short stature of patients with Prader-Willi syndrome. In addition, the aberrant control of body temperature and daytime hypersomnolence may result from hypothalamic disturbances. The number of oxytocin neurones--the putative satiety neurones--in the hypothalamic paraventricular nucleus is markedly decreased in Prader-Willi syndrome. This is presumed to be the basis of the insatiable hunger and obesity of patients with the syndrome.
Topics: Gonadotropin-Releasing Hormone; Growth Hormone-Releasing Hormone; Humans; Hypothalamus; Prader-Willi Syndrome
PubMed: 9401539
DOI: 10.1111/j.1651-2227.1997.tb18369.x -
Yi Chuan = Hereditas Oct 2022Prader-Willi syndrome (PWS) is a rare congenital developmental disorder mainly due to the absent expression of genes on the paternally inherited chromosome 15q11-q13... (Review)
Review
Prader-Willi syndrome (PWS) is a rare congenital developmental disorder mainly due to the absent expression of genes on the paternally inherited chromosome 15q11-q13 region. Most of the clinical symptoms of PWS are related to hypothalamic dysfunction, including hyperphagia, morbid obesity, mental retardation, and hypogonadism. However, the molecular genetic mechanism of PWS is not fully understood, especially the relationship between genotype and phenotype. In this review, we focus on the genetic mechanisms behind the hypothalamus dysfunction, summarizing the latest research progress of the roles of PWS candidate genes in chromosome 15q11-q13 region (NIPA1, NIPA2, TUBGCP5, CYFIP1, MAGEL2, NDN, MKRN3 and SNORD116) in hypothalamic disorders such as hyperphagia and obesity, hypogonadism, sleep-disordered breathing, growth retardation in PWS patients, to deepen the understanding of PWS syndrome and explore potential new drug targets.
Topics: Humans; Prader-Willi Syndrome; Hyperphagia; Phenotype; Genotype; Hypogonadism; Ubiquitin-Protein Ligases; Proteins
PubMed: 36384726
DOI: 10.16288/j.yczz.22-188 -
Neuroscience and Biobehavioral Reviews Dec 2015Prader-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.... (Review)
Review
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.
Topics: Animals; Appetite; Behavior; Eating; Humans; Hyperphagia; Obsessive-Compulsive Disorder; Prader-Willi Syndrome
PubMed: 26475993
DOI: 10.1016/j.neubiorev.2015.10.003