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The Journal of Clinical Endocrinology... Nov 2023Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its... (Review)
Review
CONTEXT
Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health.
OBJECTIVE
To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening.
METHODS
We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy, and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies.
RESULTS
Seven adults (age range, 18-55 years) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma, and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies.
CONCLUSION
Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present, such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged.
Topics: Adolescent; Adult; Child; Humans; Middle Aged; Young Adult; Adenocarcinoma; Fathers; Hyperphagia; Prader-Willi Syndrome; Retrospective Studies
PubMed: 37267430
DOI: 10.1210/clinem/dgad312 -
Journal of Pediatric Nursing 2017
Review
Topics: Child; Epilepsy; Female; Humans; Intellectual Disability; Male; Nurses, Pediatric; Obesity, Morbid; Prader-Willi Syndrome
PubMed: 28549751
DOI: 10.1016/j.pedn.2017.04.007 -
Neurologic Clinics Feb 1989People with Prader-Willi syndrome exhibit infantile hypotonia and failure to thrive, genital hypoplasia, childhood-onset obesity, mental deficiency and behavioral... (Review)
Review
People with Prader-Willi syndrome exhibit infantile hypotonia and failure to thrive, genital hypoplasia, childhood-onset obesity, mental deficiency and behavioral abnormalities, hypogonadism, short stature, and characteristic dysmorphology. In over half the affected individuals, prometaphase chromosome analysis reveals a small interstitial deletion of chromosome 15q, del 15(q11-q12); with most of the remaining patients showing apparently normal chromosomes. Molecular genetic technology is currently being applied to the relevant region of chromosome 15 to determine if there is etiologic heterogeneity and to seek a consistent diagnostic marker. Diagnosis at this time is primarily based upon clinical criteria.
Topics: Adolescent; Adult; Child Development; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 15; Genetic Markers; Humans; Infant; Infant, Newborn; Male; Prader-Willi Syndrome; Translocation, Genetic
PubMed: 2646521
DOI: No ID Found -
Current Problems in Pediatrics Jan 1984
Review
Topics: Abnormalities, Multiple; Adolescent; Child; Child, Preschool; Diagnosis, Differential; Dwarfism, Pituitary; Facial Expression; Female; Humans; Hypogonadism; Infant; Infant, Newborn; Intellectual Disability; Male; Muscle Hypotonia; Obesity; Prader-Willi Syndrome; Social Behavior Disorders
PubMed: 6365470
DOI: 10.1016/0045-9380(84)90043-4 -
Clinical Anatomy (New York, N.Y.) Jul 2016Prader-Willi Syndrome (PWS) is estimated to affect 400,000 people worldwide. First described clinically in 1956, PWS is now known to be a result of a genetic mutation,... (Review)
Review
Prader-Willi Syndrome (PWS) is estimated to affect 400,000 people worldwide. First described clinically in 1956, PWS is now known to be a result of a genetic mutation, involving Chromosome 15. The phenotypical appearance of individuals with the syndrome follows a similar developmental course. During infancy, universal hypotonia accompanied by feeding problems, hypogonadism, and dolichocephaly are evident. Characteristic facial features such as narrow bifrontal diameter, almond-shaped eyes, and small mouth (with downturned corners and thin upper lip) may also be evident at this stage. In early childhood, the craniofacial features become more obvious and a global developmental delay is observed. Simultaneously, individuals develop hyperphagia that leads to excessive or rapid weight gain, which, if untreated, exists throughout their lifespan and may predispose them to numerous, serious health issues. The standard tool for differential diagnosis of PWS is genetic screening; however, clinicians also need to be aware of the characteristic features of this disorder, including differences between the genetic subtypes. As the clinical manifestations of the syndrome vary between individuals and become evident at different developmental time points, early assessment is hindered. This article focuses on the clinical and anatomical manifestations of the syndrome and highlights the areas of discrepancy and limitations within the existing literature. Clin. Anat. 29:590-605, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Dentition; Facies; Humans; Hypopigmentation; Musculoskeletal Abnormalities; Phenotype; Prader-Willi Syndrome; Vision, Ocular
PubMed: 26749552
DOI: 10.1002/ca.22686 -
Revista Paulista de Pediatria : Orgao... 2018To carry out a review about Prader-Willi Syndrome based on the most recent data about the subject and to give recommendation for the general pediatricians for early... (Review)
Review
OBJECTIVE
To carry out a review about Prader-Willi Syndrome based on the most recent data about the subject and to give recommendation for the general pediatricians for early diagnoses and follow-up.
DATA SOURCES
Scientific articles in the PubMed and SciELO databases. The research was not limited to a specific time period and included all articles in such databases.
DATA SYNTHESIS
The Prader-Willi Syndrome (PWS) is a rare genetic disorder resulting from the loss of imprinted gene expression within the paternal chromosome 15q11-q13. PWS is characterized by endocrine abnormalities, such as growth hormone (GH) deficiency, obesity, central adrenal insufficiency, hypothyroidism, hypogonadism and complex behavioral and intellectual difficulties. PWS individuals also may present other comorbidities, such as sleep disorders, scoliosis, constipation, dental issues and coagulation disorders. The follow-up protocol of the Children's Institute at Universidade de São Paulo is based on four main pillars: diet, exercise, recombinant human growth hormone (rhGH) therapy and behavioral and cognitive issues. The diet must include a caloric restriction of 900 kcal/day, according to the Prader-Willi Eating Pyramid and exercise plan is focused on daily aerobic exercises and postural therapy. The rhGH therapy is highly recommended by the international scientific literature and must be started as soon as the diagnostic is made. The management of behavioral issues is based on strategies to establish routine and rules.
CONCLUSIONS
If the general pediatrician becomes more familiar with PWS, the diagnosis and treatment will start earlier, which is essential to improve the quality of life and care for these individuals.
Topics: Humans; Pediatrics; Practice Guidelines as Topic; Prader-Willi Syndrome
PubMed: 30365815
DOI: 10.1590/1984-0462/;2018;36;3;00003 -
International Journal of Molecular... Feb 2021Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical... (Review)
Review
Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical manifestations are reported, such as short stature, cognitive and behavioral disability, temperature instability, hypotonia, hypersomnia, hyperphagia, and multiple endocrine abnormalities, including growth hormone deficiency and hypogonadism. The hypogonadism in PWS is due to central and peripheral mechanisms involving the hypothalamus-pituitary-gonadal axis. The early diagnosis and management of hypogonadism in PWS are both important for physicians in order to reach a better quality of life for these patients. The aim of this study is to summarize and investigate causes and possible therapies for hypogonadism in PWS. Additional studies are further needed to clarify the role of different genes related to hypogonadism and to establish a common and evidence-based therapy.
Topics: Chromosome Aberrations; Hormones; Humans; Hypogonadism; Prader-Willi Syndrome
PubMed: 33671467
DOI: 10.3390/ijms22041993 -
Sleep Medicine Reviews Jun 2021Prader-Willi Syndrome (PWS) is a complex genetic disorder with multiple cognitive, behavioral and endocrine dysfunctions. Sleep alterations and sleep disorders such as... (Meta-Analysis)
Meta-Analysis Review
Prader-Willi Syndrome (PWS) is a complex genetic disorder with multiple cognitive, behavioral and endocrine dysfunctions. Sleep alterations and sleep disorders such as Sleep-disordered breathing and Central disorders of hypersomnolence are frequently recognized (either isolated or in comorbidity). The aim of the review is to highlight the pathophysiology and the clinical features of sleep disorders in PWS, providing the basis for early diagnosis and management. We reviewed the genetic features of the syndrome and the possible relationship with sleep alterations in animal models, and we described sleep phenotypes, diagnostic tools and therapeutic approaches in humans. Moreover, we performed a meta-analysis of cerebrospinal fluid orexin levels in patients with PWS; significantly lower levels of orexin were detected in PWS with respect to control subjects (although significantly higher than the ones of narcoleptic patients). Sleep disorders in humans with PWS are multifaceted and are often the result of different mechanisms. Since hypothalamic dysfunction seems to partially influence metabolic, respiratory and sleep/wake characteristics of this syndrome, additional studies are required in this framework.
Topics: Animals; Disorders of Excessive Somnolence; Humans; Models, Animal; Prader-Willi Syndrome; Sleep Apnea Syndromes; Sleep Wake Disorders
PubMed: 33567377
DOI: 10.1016/j.smrv.2021.101432 -
Journal of Clinical Research in... 2014Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is... (Review)
Review
Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.
Topics: Adolescent; Adult; Body Composition; Child; Child, Preschool; Cognition Disorders; Female; Growth Hormone; Human Growth Hormone; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Male; Obesity, Morbid; Prader-Willi Syndrome
PubMed: 24932597
DOI: 10.4274/Jcrpe.1228 -
Annali Dell'Istituto Superiore Di Sanita 1999Prader-Willi syndrome (PWS) is the most frequent cause of secondary obesity, characterized by neonatal hypotonia, dysmorphic facies, acromicria, hypogonadism, stunted... (Review)
Review
Prader-Willi syndrome (PWS) is the most frequent cause of secondary obesity, characterized by neonatal hypotonia, dysmorphic facies, acromicria, hypogonadism, stunted growth, obesity, behavioural disturbances and cognitive impairment. Clinical diagnosis is confirmed by alteration of imprinted genes on the proximal long arm of chromosome 15 (15q11-13) for deletion, translocation, uniparental disomy for maternal chromosome 15 or imprinting center defect. Methylation test is the most reliable test for diagnosis. This issue explains diagnostic tests, clinical, metabolic, endocrinological features, and the most frequent complications observed in this syndrome. Precocious diagnosis and multidisciplinary approach allow in these patients to prevent the severe obesity and linked complications.
Topics: Diagnosis, Differential; Growth; Growth Hormone; Humans; Intellectual Disability; Phenotype; Prader-Willi Syndrome; Puberty; Sex Factors
PubMed: 10645655
DOI: No ID Found