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Open Biology Sep 2020Prader-Willi syndrome (PWS) is caused by the loss of function of the paternally inherited 15q11-q13 locus. This region is governed by genomic imprinting, a phenomenon in... (Review)
Review
Prader-Willi syndrome (PWS) is caused by the loss of function of the paternally inherited 15q11-q13 locus. This region is governed by genomic imprinting, a phenomenon in which genes are expressed exclusively from one parental allele. The genomic imprinting of the 15q11-q13 locus is established in the germline and is largely controlled by a bipartite imprinting centre. One part, termed the Prader-Willi syndrome imprinting center (PWS-IC), comprises a CpG island that is unmethylated on the paternal allele and methylated on the maternal allele. The second part, termed the Angelman syndrome imprinting centre, is required to silence the PWS_IC in the maternal germline. The loss of the paternal contribution of the imprinted 15q11-q13 locus most frequently occurs owing to a large deletion of the entire imprinted region but can also occur through maternal uniparental disomy or an imprinting defect. While PWS is considered a contiguous gene syndrome based on large-deletion and uniparental disomy patients, the lack of expression of only non-coding RNA transcripts from the may be the primary cause of PWS. Patients with small atypical deletions of the paternal cluster alone appear to have most of the PWS related clinical phenotypes. The loss of the maternal contribution of the 15q11-q13 locus causes a separate and distinct condition called Angelman syndrome. Importantly, while much has been learned about the regulation and expression of genes and transcripts deriving from the 15q11-q13 locus, there remains much to be learned about how these genes and transcripts contribute at the molecular level to the clinical traits and developmental aspects of PWS that have been observed.
Topics: Biomarkers; Chromosomes, Human, Pair 15; Disease Management; Disease Susceptibility; Epigenesis, Genetic; Gene Expression Regulation; Genetic Association Studies; Genetic Loci; Genomic Imprinting; Humans; Phenotype; Prader-Willi Syndrome; RNA, Untranslated
PubMed: 32961075
DOI: 10.1098/rsob.200195 -
Journal of Medical Genetics Nov 1997Prader-Willi syndrome is a complex disorder affecting multiple systems with many manifestations relating to hypothalamic insufficiency. Major findings include infantile... (Review)
Review
Prader-Willi syndrome is a complex disorder affecting multiple systems with many manifestations relating to hypothalamic insufficiency. Major findings include infantile hypotonia, developmental delay and mental retardation, behaviour disorder, characteristic facial appearance, obesity, hypogonadism, and short stature. Obesity and the behavioural problems are the major causes of morbidity and mortality. Prader-Willi syndrome is caused by abnormalities of the imprinted region of proximal 15q and results from absence of the normally active paternal genes in this region. Such absence results from paternal interstitial deletion, maternal uniparental disomy, or a mutation or other abnormality in the imprinting process. Diagnostic identification of all causes has become available in recent years, permitting early detection and institution of appropriate management. This testing has permitted recent identification of some phenotypic differences among affected subjects of different race and between those with deletions and uniparental disomy as a cause.
Topics: Humans; Prader-Willi Syndrome
PubMed: 9391886
DOI: 10.1136/jmg.34.11.917 -
Current Opinion in Endocrinology,... Feb 2020Prader Willi syndrome is characterized not only by hyperphagia frequently resulting in obesity, but also by endocrine dysfunction across a variety of axes. This article... (Review)
Review
PURPOSE OF REVIEW
Prader Willi syndrome is characterized not only by hyperphagia frequently resulting in obesity, but also by endocrine dysfunction across a variety of axes. This article reviews the most recent literature regarding possible causes of hyperphagia and the nature of endocrinopathies seen in Prader Willi syndrome, as well as current research into possible therapies.
RECENT FINDINGS
Investigation into neurologic, metabolic and hormonal drivers of hyperphagia and obesity has revealed new insights and clarified underlying pathophysiology. Additional studies continue to elucidate the hormonal deficiencies seen in the syndrome, allowing for improvements in clinical care.
SUMMARY
The underlying causes of the hyperphagia and progressive obesity frequently seen in Prader Willi Syndrome are largely unknown and likely multifactorial. Understanding the hormonal and metabolic drivers at work in PWS, as well as the nature of other hormonal dysfunction seen in the syndrome is necessary to guide current management and future research directions.
Topics: Drugs, Investigational; Endocrine System; Humans; Hyperphagia; Obesity; Prader-Willi Syndrome; Therapies, Investigational
PubMed: 31815782
DOI: 10.1097/MED.0000000000000517 -
Neonatal Network : NN May 2017The imprinting disorder, Prader-Willi syndrome, is a condition associated with the gene region 15q11.2-q.13. The phenotype includes multiple characteristics, most of... (Review)
Review
The imprinting disorder, Prader-Willi syndrome, is a condition associated with the gene region 15q11.2-q.13. The phenotype includes multiple characteristics, most of which are endocrine-related. An accurate diagnosis is done mostly through pre- or postnatal genetic testing. Management is mainly aimed at correcting the endocrine dysfunctions present in these patients. Genetic testing is also important to distinguish between the different causes and to calculate the recurrence risk for parents with affected children. Although a lot has been discovered and this syndrome can be managed to a satisfactory degree, further research is still important especially regarding new potential treatments with greater efficiency and reduced invasiveness. The neonatal nurse has an important role because the management requires thorough monitoring as well as high compliance from both the patient and the carers. Thus, it is essential for the neonatal nurse to have a good knowledge of this condition.
Topics: Female; Genetic Counseling; Genetic Testing; Genomic Imprinting; Humans; Infant, Newborn; Neonatal Nursing; Neonatal Screening; Phenotype; Prader-Willi Syndrome; Pregnancy; Prenatal Diagnosis
PubMed: 28494825
DOI: 10.1891/0730-0832.36.3.134 -
American Family Physician Sep 2005To complement the 2005 Annual Clinical Focus on medical genomics, AFP is publishing a series of short reviews on genetic syndromes. This series was designed to increase... (Review)
Review
To complement the 2005 Annual Clinical Focus on medical genomics, AFP is publishing a series of short reviews on genetic syndromes. This series was designed to increase awareness of these diseases so that family physicians can recognize and diagnose children with these disorders and understand the type of care they might require in the future. This review discusses Prader-Willi syndrome.
Topics: Child; Chromosomes, Human, Pair 15; Humans; Prader-Willi Syndrome
PubMed: 16156341
DOI: No ID Found -
Journal of Paediatrics and Child Health Aug 1999Prader-Willi syndrome is a multi system disorder characterized by neonatal hypotonia, later obesity, hyperphagia and mental retardation. It occurs sporadically, either... (Review)
Review
Prader-Willi syndrome is a multi system disorder characterized by neonatal hypotonia, later obesity, hyperphagia and mental retardation. It occurs sporadically, either as a result of microdeletion of chromosome 15p (70%) or as a result of maternal disomy of chromosome 15 (30%). The major problems encountered by parents are those of hyperphagia, food-seeking and obesity, and conduct disorder, particularly tantrums or oppositional behaviour.
Topics: Adolescent; Adult; Attention Deficit and Disruptive Behavior Disorders; Child; Chromosomes, Human, Pair 15; Female; Genomic Imprinting; Humans; Hyperphagia; Infant, Newborn; Male; Obsessive-Compulsive Disorder; Prader-Willi Syndrome
PubMed: 10457284
DOI: 10.1046/j.1440-1754.1999.00397.x -
Clinical Autonomic Research : Official... Jun 2023Prader-Willi syndrome is a complex neurodevelopmental genetic disorder due to lack of paternal expression of critical imprinted genes in the 15q11.2-q13.1 chromosomal... (Review)
Review
INTRODUCTION
Prader-Willi syndrome is a complex neurodevelopmental genetic disorder due to lack of paternal expression of critical imprinted genes in the 15q11.2-q13.1 chromosomal region, generally from a paternal deletion. Predominant features include infantile hypotonia, a poor suck with failure to thrive, craniofacial features, and developmental and behavioral problems including self-injury and childhood onset of obesity. In addition to severe obesity, patients with PWS present with other symptoms of autonomic nervous system dysfunction.
METHODS
We examined the features seen in Prader-Willi syndrome and searched the literature for evidence of autonomic nervous system involvement in this rare obesity-related disorder and illustrative findings possibly due to autonomic nervous system dysfunction. Additionally, we reviewed the literature in relation to childhood obesity syndromes and compared those syndromes to the syndromic obesity found in Prader-Willi syndrome.
RESULTS
We report autonomic nervous system-related symptoms associated with childhood obesity impacting features seen in Prader-Willi syndrome and possibly other obesity-related genetic syndromes. We compiled evidence of both an autonomic route for the obesity seen in PWS and other autonomic nervous system-related dysfunctions. These include decreased salvation, sleep disordered breathing, increased pain and thermal threshold instability, delayed gastric emptying, altered blood pressure readings, and pupillary constriction responses as evidence of autonomic nervous system involvement.
CONCLUSIONS
We summarized and illustrated findings of autonomic nervous system dysfunction in Prader-Willi syndrome and other obesity-related syndromes and genetic factors that may play a causative role in development.
Topics: Humans; Child; Prader-Willi Syndrome; Pediatric Obesity
PubMed: 36515769
DOI: 10.1007/s10286-022-00909-7 -
Archives of Disease in Childhood Jan 1994
Review
Topics: Age Factors; Chromosomes, Human, Pair 15; Female; Gene Deletion; Humans; Male; Prader-Willi Syndrome
PubMed: 8110011
DOI: 10.1136/adc.70.1.58 -
Frontiers in Endocrinology 2023Prader-Willi syndrome (PWS, OMIM176270) is a rare genetic disorder with recognizable dysmorphic features and multisystemic consequences such as endocrine, neurocognitive... (Review)
Review
Prader-Willi syndrome (PWS, OMIM176270) is a rare genetic disorder with recognizable dysmorphic features and multisystemic consequences such as endocrine, neurocognitive and metabolic ones. Although most patients with Prader-Willi syndrome exhibit hypogonadotropic hypogonadism, there is variability regarding sexual maturation, with precocious puberty occurring in rare cases. Our aim is to elaborate a thorough review of Prader-Willi patients with central precocious puberty, in order to raise awareness of such cases and to enhance our knowledge regarding the diagnosis and prompt treatment of this particular PWS patients.
Topics: Humans; Prader-Willi Syndrome; Puberty, Precocious; Sexual Maturation; Hypogonadism; Knowledge
PubMed: 37251677
DOI: 10.3389/fendo.2023.1150323 -
Missouri Medicine 2024Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental disorder with multisystem impact and a unique behavior profile that evolves over the life span.... (Review)
Review
Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental disorder with multisystem impact and a unique behavior profile that evolves over the life span. Beyond the primary care needs of all children and adults, the unique medical concerns and management needs of those with PWS are best served in a multidisciplinary academic center. Our PWS center has provided care for individuals with PWS and their families since 1981. Our growth hormone studies contributed to growth hormone supplementation becoming standard of care in this country. Here, in collaboration with the primary care provider, early childhood intervention programs, schools and local parent organizations, solid, patient-centered care for affected individuals and their families can be provided across the life-span. The purpose of this article is to provide a brief overview of PWS and the attendant medical and behavior management challenges attendant to the disorder.
Topics: Prader-Willi Syndrome; Humans; Child; Human Growth Hormone
PubMed: 38854617
DOI: No ID Found