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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a highly heritable and genetically heterogeneous disorder. Here we investigated the contribution of copy number variation to obesity in 300 Caucasian patients with severe early-onset obesity, 143 of whom also had developmental delay. Large (>500 kilobases), rare (<1%) deletions were significantly enriched in patients compared to 7,366 controls (P < 0.001). We identified several rare copy number variants that were recurrent in patients but absent or at much lower prevalence in controls. We identified five patients with overlapping deletions on chromosome 16p11.2 that were found in 2 out of 7,366 controls (P < 5 x 10(-5)). In three patients the deletion co-segregated with severe obesity. Two patients harboured a larger de novo 16p11.2 deletion, extending through a 593-kilobase region previously associated with autism and mental retardation; both of these patients had mild developmental delay in addition to severe obesity. In an independent sample of 1,062 patients with severe obesity alone, the smaller 16p11.2 deletion was found in an additional two patients. All 16p11.2 deletions encompass several genes but include SH2B1, which is known to be involved in leptin and insulin signalling. Deletion carriers exhibited hyperphagia and severe insulin resistance disproportionate for the degree of obesity. We show that copy number variation contributes significantly to the genetic architecture of human obesity.
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PMID:Large, rare chromosomal deletions associated with severe early-onset obesity. 2088 Jan 23

Ipercaloric diet and reduced physical activity have driven the rise in the prevalence of childhood obesity over a relatively short time interval. Family and twin studies have led to the conclusion that the strong predictive value of parental body mass index (BMI) mainly stems from genetic rather than environmental factors. Whereas the common polygenic obesity arises when an individual genetic make-up is susceptible to an environment that promotes energy consumption over energy expenditure, monogenic obesity, on the contrary, is the obesity associated with a single gene mutation, which is sufficient by itself to cause weight gain in a food abundant context. Genes involved in the leptin-melanocortin pathway are often mutated in these cases. The cumulative prevalence of monogenic obesity among children with severe obesity is about 5%. Recently, deletions in the region p11.2 of the chromosome 16 encompassing the gene SH2B1, which is involved in the leptin and insulin signaling, have been reported in about 0.5% of children with severe early-onset obesity. These patients show extreme hyperphagia, severe insulin resistance and, in some cases, mild developmental delay.
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PMID:Chromosome 16p11.2 deletions: another piece in the genetic puzzle of childhood obesity. 2054 Jul 50

Monosomy 1p36 is the most common terminal deletion syndrome seen in humans, occurring in approximately 1 in 5,000 live births. Common features include mental retardation, characteristic dysmorphic features, hypotonia, seizures, hearing loss, heart defects, cardiomyopathy, and behavior abnormalities. Similar phenotypes are seen among patients with a variety of deletion sizes, including terminal and interstitial deletions, complex rearrangements, and unbalanced translocations. Consequently, critical regions harboring causative genes for each of these features have been difficult to identify. Here we report on five individuals with 200-823 kb overlapping deletions of proximal 1p36.33, four of which are apparently de novo. They present with features of monosomy 1p36, including developmental delay and mental retardation, dysmorphic features, hypotonia, behavioral abnormalities including hyperphagia, and seizures. The smallest region of deletion overlap is 174 kb and contains five genes; these genes are likely candidates for some of the phenotypic features in monosomy 1p36. Other genes deleted in a subset of the patients likely play a contributory role in the phenotypes, including GABRD and seizures, PRKCZ and neurologic features, and SKI and dysmorphic and neurologic features. Characterization of small deletions is important for narrowing critical intervals and for the identification of causative or candidate genes for features of monosomy 1p36 syndrome.
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PMID:Refinement of causative genes in monosomy 1p36 through clinical and molecular cytogenetic characterization of small interstitial deletions. 2063 59

Obesity in humans is a complex polygenic trait with high inter-individual heritability estimated at 40-70%. Candidate gene, DNA linkage and genome-wide association studies (GWAS) have allowed for the identification of a large set of genes and genomic regions associated with obesity. Structural chromosome abnormalities usually result in congenital anomalies, growth retardation and developmental delay. Occasionally, they are associated with hyperphagia and obesity rather than growth delay. We report four new individuals with structural chromosome abnormalities involving 10q22.3-23.2, 16p11.2 and Xq27.1-q28 chromosomal regions with early childhood obesity and developmental delay. We also searched and summarized the literature for structural chromosome abnormalities reported in association with childhood obesity.
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PMID:Structural Chromosome Abnormalities Associated with Obesity: Report of Four New subjects and Review of Literature. 2204 67

Prader-Willi syndrome is characterized by severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal insufficiency; characteristic facial features; early-childhood onset obesity and hyperphagia; developmental delay/mild intellectual disability; short stature; and a distinctive behavioral phenotype. Sleep abnormalities and scoliosis are common. Growth hormone insufficiency is frequent, and replacement therapy provides improvement in growth, body composition, and physical attributes. Management is otherwise largely supportive. Consensus clinical diagnostic criteria exist, but diagnosis should be confirmed through genetic testing. Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13 through paternal deletion of this region (65-75% of individuals), maternal uniparental disomy 15 (20-30%), or an imprinting defect (1-3%). Parent-specific DNA methylation analysis will detect >99% of individuals. However, additional genetic studies are necessary to identify the molecular class. There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features. Sibling recurrence risk is typically <1%, but higher risks may pertain in certain cases. Prenatal diagnosis is available.
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PMID:Prader-Willi syndrome. 2223 28

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features include neonatal hypotonia, distinctive facial features, overall developmental delay, and poor growth in infancy, followed by overeating with severe obesity, short stature, and hypogonadism later in development. This paper reviews recent updates regarding the genetic aspects of this disorder. Three mechanisms (paternal deletion, maternal disomy, and deficient imprinting) are recognized. Maternal disomy can arise because of 4 possible mechanisms: trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and postfertilization mitotic nondisjunction (Mit). Recently, TR/GC caused by nondisjunction at maternal meiosis 1 has been identified increasingly, as a result of advanced maternal childbearing age in Korea. We verified that the d3 allele increases the responsiveness of the growth hormone (GH) receptor to endogenous GH. This paper also provides an overview of endocrine dysfunctions in children with PWS, including GH deficiency, obesity, sexual development, hypothyroidism, and adrenal insufficiency, as well as the effects of GH treatment. GH treatment coupled with a strictly controlled diet during early childhood may help to reduce obesity, improve neurodevelopment, and increase muscle mass. A more active approach to correct these hormone deficiencies would benefit patients with PWS.
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PMID:Endocrine problems in children with Prader-Willi syndrome: special review on associated genetic aspects and early growth hormone treatment. 2284 16

Obesity is a major threat to public health worldwide, and there is now mounting evidence favoring a role for the central nervous system (CNS) in weight control. A causal relationship has been recognized in both monogenic (e.g., BDNF, TRKB, and SIM1 deficiencies) and syndromic forms of obesity [e.g., Prader-Willi syndrome (PWS)]. Syndromic obesity arising from chromosomal abnormalities, that typically also affect learning and development, are often associated with congenital malformations and behavioral characteristics. We report on nine unrelated patients with a diagnosis of learning disability and/or developmental delay (DD) in addition to obesity that were found to have copy number variants (CNVs) by single nucleotide polymorphism array-based analysis. Each patient also had a distinct and complex phenotype, and most had hypotonia and other neuroendocrine issues, such as hyperphagia and hypogonadism. Molecular and clinical characterization of these patients enabled us to determine with confidence that the CNVs we observed were pathogenic or likely to be pathogenic. Overall, the CNVs reported here encompassed a candidate gene or region (e.g., SIM1) that has been reported in patients associating obesity and DD and/or intellectual disability (ID) and novel candidate genes and regions.
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PMID:Obesity with associated developmental delay and/or learning disability in patients exhibiting additional features: report of novel pathogenic copy number variants. 2340 28

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.
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PMID:Endocrine manifestations and management of Prader-Willi syndrome. 2396 41

Heat stroke is a medical emergency characterized primarily by an elevated core temperature associated with a systemic inflammatory response, which causes multiple organ dysfunction in which encephalopathy predominates. If it is not early treated has high mortality. The Prader-Willi syndrome is a multisystem genetic disorder secondary to an abnormality in long arm chromosome 15 (15q11-q13), characterized by neonatal central hypotonia, developmental delay, hypogonadism, hyperphagia and obesity. These patients are susceptible to developing thermoregulatory problems. We report the case of a 5-month-old infant, in whom a diagnosis of Prader-Willi syndrome was established in the course of a febrile episode without known focus, who developed multiorganic failure and rhabdomyolysis secondary to hyperthermia.
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PMID:[Multiorgan failure associated with hyperthermia in an infant with Prader-Willi syndrome. case report]. 2409 35

Prader Willi syndrome (PWS) is a genetic condition caused by loss of the paternal copy of a region of imprinted genes on chromosome 15. There is severe muscular hypotonia in the neonatal period, with the onset of hyperphagia and food-seeking behaviour in childhood. All individuals with PWS have developmental delay. Without careful control of food intake and the food environment, individuals with PWS become morbidly obese and are likely to die as young adults from the complications of obesity. The aims of growth hormone (GH) treatment in PWS are distinct from the use of GH in other conditions-although GH does increase final height in PWS, the main benefits of treatment are improved body composition and better exercise capacity, which can help with the aim of preventing obesity. GH trials in PWS have demonstrated improved muscle bulk, reduced fat mass and increased levels of physical activity. GH has also been demonstrated to improve attainment of developmental and cognitive milestones in children with PWS. GH treatment appears to change respiratory status in PWS, possibly because of growth of lymphoid tissue at the start of treatment. Respiratory assessment is recommended prior to, and just after starting GH treatment. Ideal age for starting GH is not clear, although there has been a trend towards starting at younger ages. It may be that GH treatment in childhood confers benefits into adult life. There are less data to support continuing GH treatment into adult life.
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PMID:What is the value of growth hormone therapy in Prader Willi syndrome? 2416 7


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