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Nature Reviews. Disease Primers Jun 2023Imprinting disorders (ImpDis) are congenital conditions that are characterized by disturbances of genomic imprinting. The most common individual ImpDis are Prader-Willi... (Review)
Review
Imprinting disorders (ImpDis) are congenital conditions that are characterized by disturbances of genomic imprinting. The most common individual ImpDis are Prader-Willi syndrome, Angelman syndrome and Beckwith-Wiedemann syndrome. Individual ImpDis have similar clinical features, such as growth disturbances and developmental delay, but the disorders are heterogeneous and the key clinical manifestations are often non-specific, rendering diagnosis difficult. Four types of genomic and imprinting defect (ImpDef) affecting differentially methylated regions (DMRs) can cause ImpDis. These defects affect the monoallelic and parent-of-origin-specific expression of imprinted genes. The regulation within DMRs as well as their functional consequences are mainly unknown, but functional cross-talk between imprinted genes and functional pathways has been identified, giving insight into the pathophysiology of ImpDefs. Treatment of ImpDis is symptomatic. Targeted therapies are lacking owing to the rarity of these disorders; however, personalized treatments are in development. Understanding the underlying mechanisms of ImpDis, and improving diagnosis and treatment of these disorders, requires a multidisciplinary approach with input from patient representatives.
PubMed: 37386011
DOI: 10.1038/s41572-023-00443-4 -
Current Opinion in Pulmonary Medicine Nov 2023Sleep disorders in Prader-Willi syndrome (PWS) range from respiratory to neurological disorders of sleep. We now recognize the role of excessive daytime sleepiness...
PURPOSE OF REVIEW
Sleep disorders in Prader-Willi syndrome (PWS) range from respiratory to neurological disorders of sleep. We now recognize the role of excessive daytime sleepiness (present in the infant period and throughout life), and a modified narcolepsy phenotype with or without cataplexy. Disordered sleep in PWS may present with symptoms pervasive to daily function, including inattention at school, irritability, and behavioral outbursts. This review highlights the spectrum of sleep disordered breathing and neurological disorders of sleep in individuals with PWS as well as the current knowledge of management.
RECENT FINDINGS
This article covers the literature characterizing sleep disorders in PWS, including treatment strategies.
SUMMARY
The review highlights the importance of considering disorders of sleep in PWS and the current treatment options.
PubMed: 37700664
DOI: 10.1097/MCP.0000000000001018 -
Frontiers in Endocrinology 2023
Topics: Humans; Obesity; Prader-Willi Syndrome
PubMed: 38239989
DOI: 10.3389/fendo.2023.1349582 -
Gastroenterology Clinics of North... Dec 2023Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic... (Review)
Review
Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders. Additional therapies, including metreleptin and setmelanotide, that target defects within the leptin signaling pathway can effectively synergize with lifestyle efforts to treat monogenic disorders of leptin, leptin receptor, proopiomelanocortin (POMC), and proprotein convertase subtilisin/kexin type 1 (PCSK1) and syndromic conditions, such as the ciliopathies Bardet-Biedl and Alström syndromes, whose pathophysiological mechanisms also converge on the leptin pathway. Investigational treatments for Prader-Willi syndrome target specific defects caused by reduced expression of paternally derived genes within the chromosome 15q region.
Topics: Humans; Leptin; Obesity; Prader-Willi Syndrome
PubMed: 37919024
DOI: 10.1016/j.gtc.2023.08.005 -
Annals of Translational Medicine Dec 2023
PubMed: 38213817
DOI: 10.21037/atm-23-1718 -
Endocrine Connections Jun 2024Prader Willi syndrome (PWS) is a rare orphan disease and complex genetic neurodevelopmental disorder, with a birth incidence of approximately 1 in 10,000-30,000.... (Review)
Review
Prader Willi syndrome (PWS) is a rare orphan disease and complex genetic neurodevelopmental disorder, with a birth incidence of approximately 1 in 10,000-30,000. Management of people with PWS requires a multi-disciplinary approach, ideally through a multi-disciplinary team (MDT) clinic with community support. Hypotonia, poor feeding and faltering growth are characteristic features in the neonatal period, followed by hyperphagia and risk of rapid weight gain later in childhood. Children and adolescents (CA) with PWS usually display developmental delay and mild learning disability, and can develop endocrinopathies, scoliosis, respiratory difficulties (both central and obstructive sleep apnoea), challenging behaviours, skin picking, and mental health issues especially into adulthood. This consensus statement is intended to be a reference document for clinicians managing children and adolescents (up to 18 years of age) with PWS. It considers the bio-psycho-social domains of diagnosis, clinical assessment, and management in the paediatric setting as well as during and after transition to adult services. The guidance has been developed from information gathered from peer-reviewed scientific reports and from the expertise of a range of experienced clinicians in the United Kingdom and Ireland involved in the care of patients with PWS.
PubMed: 38838713
DOI: 10.1530/EC-24-0091