scholarly journals Prader-Willi syndrome: an update on obesity and endocrine problems

2021 ◽  
Vol 26 (4) ◽  
pp. 227-236
Author(s):  
Su Jin Kim ◽  
Sung Yoon Cho ◽  
Dong-Kyu Jin
Keyword(s):  
Behavioral Problems ◽  
Genetic Disorder ◽  
Nutritional Therapy ◽  
Hormone Deficiency ◽  
Endocrine Disorders ◽  
Prader Willi Syndrome ◽  
Metabolic Complications ◽  
Obstructive Sleep ◽  
History Of ◽  
Complex Genetic Disorder

Prader-Willi syndrome (PWS) is a rare complex genetic disorder that results from a lack of expression of the paternally inherited chromosome 15q11-q13. PWS is characterized by hypotonia and feeding difficulty in early infancy and development of morbid obesity aggravated by uncontrolled hyperphagia after childhood and adolescent. Dysmorphic facial features, delayed motor and language development, various degrees of cognitive impairment, and behavioral problems are common in PWS. Without early, intensive nutritional therapy along with behavioral modification, PWS patients develop severe obesity associated with type 2 diabetes, obstructive sleep apnea, right-side heart failure, and other obesity-related metabolic complications. Hypothalamic dysfunction in PWS can lead to several endocrine disorders, including short stature with growth hormone deficiency, hypothyroidism, central adrenal insufficiency, and hypogonadism. In this review, we discuss the natural history of PWS and the mechanisms of hyperphagia and obesity. We also provide an update on obesity treatments and recommendations for screening and monitoring of various endocrine problems that can occur in PWS.

scholarly journals Hypogonadism in Patients with Prader Willi Syndrome: A Narrative Review

2021 ◽  
Vol 22 (4) ◽  
pp. 1993
Author(s):  
Luigi Napolitano ◽  
Biagio Barone ◽  
Simone Morra ◽  
Giuseppe Celentano ◽  
Roberto La Rocca ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Hormone Deficiency ◽  
Evidence Based ◽  
Prader Willi Syndrome ◽  
Complex Genetic Disorder ◽  
Evidence Based Therapy ◽  
Behavioral Disability

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.

845 Progressive external ophthalmoplegia in sleep apnea presenting as floppy eyelid syndrome

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A329-A329
Author(s):  
Pratibha Anne ◽  
Rupa Koothirezhi ◽  
Ugorji Okorie ◽  
Minh Tam Ho ◽  
Brittany Monceaux ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Surgical Treatment ◽  
Sleep Apnea ◽  
Genetic Disorder ◽  
Deltoid Muscle ◽  
Progressive External Ophthalmoplegia ◽  
Ataxic Gait ◽  
Pressure Setting ◽  
Obstructive Sleep ◽  
History Of

Abstract Introduction Floppy eye lid syndrome (FES) is known to be associated with Obstructive sleep apnea (OSA) and chronic progressive external ophthalmoplegia (CPEO) is a rare genetic disorder with mitochondrial myopathy that may present with isolated eye lid ptosis in the initial stages. In a patient with loud snoring and obesity, treating obstructive sleep apnea may improve Floppy eyelid syndrome. Report of case(s) 52-year-old African – American male with past medical history of Hypertension, obesity, glaucoma, CPEO status bilateral blepharoplasty with failed surgical treatment. Patient was referred to Sleep medicine team to rule out Obstructive Sleep Apnea aa a cause of possible underlying FES and residual ptosis. On exam, patient was noted to have bilateral brow and eyelid ptosis and mild ataxic gait. MRI brain with and without contrast was unremarkable. Deltoid muscle biopsy was suggestive of possible congenital myopathy and mild denervation atrophy. Polysomnogram showed severe OSA with AHI of 74.1 per hour and patient was initiated on Auto CPAP at a pressure setting of 7–20 cm H2O. CPAP treatment improved snoring, OSA and subjective symptoms of excessive day time sleepiness but did not improve the residual ptosis. Conclusion Treatment of severe OSA in a patient previously diagnosed with CPEO and failed surgical treatment with bilateral blepharoplasty, did not alter the course of residual ptosis/ floppy eyelids even though his other sleep apnea symptoms have improved. Support (if any) 1. McNab AA. Floppy eyelid syndrome and obstructive sleep apnea. Ophthalmic Plast Reconstr Surg. 1997 Jun;13(2):98–114. doi: 10.1097/00002341-199706000-00005. PMID: 9185193.

scholarly journals Endocrine Dysfunction in Prader-Willi Syndrome: A Review with Special Reference to GH

2001 ◽  
Vol 22 (6) ◽  
pp. 787-799 ◽  
Author(s):  
Pia Burman ◽  
E. Martin Ritzén ◽  
Ann Christin Lindgren
Keyword(s):  
Replacement Therapy ◽  
Lean Body Mass ◽  
Body Mass ◽  
Genetic Disorder ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Endocrine Disorders ◽  
Prader Willi Syndrome ◽  
Gh Treatment ◽  
Pituitary Dysfunction

Abstract Prader-Willi syndrome is a genetic disorder occurring in 1 in 10,000–16,000 live-born infants. In the general population, approximately 60 people in every 1,000,000 are affected. The condition is characterized by short stature, low lean body mass, muscular hypotonia, mental retardation, behavioral abnormalities, dysmorphic features, and excessive appetite with progressive obesity. Furthermore, morbidity and mortality are high, probably as a result of gross obesity. Most patients have reduced GH secretory capacity and hypogonadotropic hypogonadism, suggesting hypothalamic-pituitary dysfunction. Replacement of GH and/or sex hormones may therefore be beneficial in Prader-Willi syndrome, and several clinical trials have now evaluated GH replacement therapy in affected children. Results of GH treatment have been encouraging: improved growth, increased lean body mass, and reduced fat mass. There was also some evidence of improvements in respiratory function and physical activity. The long-term benefits of GH treatment are, however, still to be established. Similarly, the role of sex hormone replacement therapy needs to be clarified as few data exist on its efficacy and potential benefits. In summary, Prader-Willi syndrome is a disabling condition associated with GH deficiency and hypogonadism. More active treatment of these endocrine disorders is likely to benefit affected individuals.

scholarly journals Ghrelin-Reactive Autoantibodies are elevated in Children with Prader-Willi Syndrome

2016 ◽  
Author(s):  
Gabrielle Crisp ◽  
Ohn Nyunt ◽  
Lisa Chopin ◽  
Inge Seim ◽  
Mark Harris ◽  
...  
Keyword(s):  
Pediatric Population ◽  
Genetic Disorder ◽  
Peptide Hormone ◽  
Prader Willi Syndrome ◽  
Acylated Ghrelin ◽  
Carrier Proteins ◽  
Unacylated Ghrelin ◽  
Complex Genetic Disorder ◽  
Growth Abnormalities ◽  
Insatiable Appetite

AbstractPrader-Willi Syndrome (PWS) is a complex genetic disorder characterized by developmental and growth abnormalities, insatiable appetite, and excessive eating (hyperphagia). The underlying cause of hyperphagia in PWS is currently unknown, however, elevated levels of the peptide hormone ghrelin is believed to contribute. Recently, ghrelin-reactive autoantibodies (isotype IgG) were identified in non-genetic obesity. These autoantibodies act as ghrelin carrier proteins and potentiate its orexigenic effects. Here, we describe the identification of ghrelin-reactive autoantibodies in a cohort of 16 children with PWS. In comparison to unaffected siblings, autoantibody levels are significantly increased in PWS children. We further show that autoantibody levels are unaffected by food intake, unlike plasma ghrelin which declines postprandially in both groups. Critically, we also demonstrate that the autoantibodies bind the major circulating ghrelin isoforms, unacylated ghrelin, which does not stimulate appetite, and the orexigen acylated ghrelin. In excess, unacylated ghrelin may compete with acylated ghrelin for autoantibody binding. Taken together, this is the first report on ghrelin-reactive antibodies in a pediatric population, and the first to demonstrate that the antibodies do not discriminate between orexigenic and non-orexigenic ghrelin isoforms. Our work suggests that ghrelin autoantibodies can be targeted using non-orexigenic forms of ghrelin, thereby providing a novel therapeutic target for PWS and for obesity in general.

857 Too sleepy: A pediatric case of Prader Willi Syndrome and Narcolepsy

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A333-A333
Author(s):  
Elizabeth Lam ◽  
Sonal Malhotra ◽  
Daniel Glaze
Keyword(s):  
Daytime Sleepiness ◽  
Sleep Latency ◽  
Chromosome Region ◽  
Genetic Disorder ◽  
Sleep Onset ◽  
Apnea Hypopnea Index ◽  
Prader Willi Syndrome ◽  
Obstructive Sleep ◽  
Patient Reported

Abstract Introduction Prader Willi syndrome (PWS) is a genetic disorder due to deletion of the paternal copies of genes within the chromosome region 15q11-q13. Individuals with PWS are commonly seen with obesity, sleep disordered breathing, and excessive daytime sleepiness (EDS). While the exact cause of EDS in individuals with PWS is not fully understood, there have been reports of PWS with narcolepsy-like syndrome. We report a case of a patient with PWS with findings suggesting the diagnosis of Narcolepsy Type 2. Report of case(s) Our patient is a 12-year-old male with PWS and 2nd degree heart block who was evaluated in our pediatric sleep center. He has a previous diagnosis of mild obstructive sleep apnea (OSA) with an apnea hypopnea index (oAHI) of 3.2. At 12 years of age, mother and patient reported that he had increased snoring, weight gain, EDS with a Pediatric Daytime Sleepiness Score (PDSS) of 10 and frequent refreshing naps during the daytime. Patient denied cataplexy during that visit. Subsequently, 2-week actigrapghy was performed which demonstrated an average total night sleep of 8 hours and 8 minutes. Overnight PSG with Multiple Sleep Latency Test (MSLT) demonstrated an oAHI of 4.8, total sleep time of 6.88 hours. During the MSLT, the mean sleep latency was 6.2 minutes and 5 sleep onset REM periods were observed over 5 nap opportunities. At his follow-up visit, methylphenidate was initiated after clearance by his cardiologist. Patient and mother opted for medical management of his mild OSA with Fluticisone and Montelukast. At his follow-up appointment, the patient had improvement in daytime sleepiness with a PDSS of 2 despite taking his Methylphenidate at night. Patient was instructed to switch to morning Methylphenidate dosing to optimize treatment of his EDS. Conclusion EDS is a common complaint seen in patients with PWS, however the etiology of it is not entirely understood. It is thought to be centrally mediated with components of hypersomnia and narcolepsy like-symptoms. More research is needed to better understand, diagnose and adequately treat patients with PWS and EDS. Support (if any):

Thyroid function in patients with Prader-Willi syndrome: an Italian multicenter study of 339 patients

2019 ◽  
Vol 32 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Lorenzo Iughetti ◽  
Giulia Vivi ◽  
Antonio Balsamo ◽  
Andrea Corrias ◽  
Antonino Crinò ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Genetic Disorder ◽  
Hypogonadotropic Hypogonadism ◽  
Thyroid Stimulating Hormone ◽  
Hormone Deficiency ◽  
Published Data ◽  
Prader Willi Syndrome ◽  
Thyroid Function Tests ◽  
Central Hypothyroidism

AbstractBackgroundPrader-Willi syndrome (PWS) is a genetic disorder due to loss of expression of paternally transcribed genes of the imprinted region of chromosome 15q11-13. PWS is characterized by peculiar signs and symptoms and many endocrine abnormalities have been described (growth hormone deficiency, hypogonadotropic hypogonadism). The abnormalities of thyroid function are discussed in literature and published data are discordant. The aim of our study was to report the thyroid function in patients with PWS to identify the prevalence of thyroid dysfunction.MethodsThyroid function tests were carried out in 339 patients with PWS, aged from 0.2 to 50 years. A database was created to collect personal data, anthropometric data, thyroid function data and possible replacement therapy with L-thyroxine. Subjects were classified according to thyroid function as: euthyroidism (EuT), congenital hypothyroidism (C-HT), hypothyroidism (HT – high thyroid-stimulating hormone [TSH] and low free thyroxine [fT4]), central hypothyroidism (CE-H – low/normal TSH and low fT4), subclinical hypothyroidism (SH – high TSH and normal fT4), and hyperthyroidism (HyperT – low TSH and high fT4).ResultsTwo hundred and forty-three out of 339 PWS patients were younger than 18 years (71.7%). The prevalence of thyroid dysfunction was 13.6%. Specifically, C-HT was found in four children (1.18%), HT in six patients (1.77%), CE-H in 23 patients (6.78%), SH in 13 patients (3.83%), and HyperT in none. All other subjects were in EuT (86.4%).ConclusionsHypothyroidism is a frequent feature in subjects with PWS. Thyroid function should be regularly investigated in all PWS patients both at the diagnosis and annually during follow-up.

Growth hormone deficiency and metabolic disorders after radiotherapy and chemotherapy of malignant tumors of the posterior cranial fossa

2016 ◽  
Vol 62 (2) ◽  
pp. 12-24
Author(s):  
Tatiana Y. Tselovalnikova ◽  
Maria G. Pavlova ◽  
Alexey V. Zilov ◽  
Alla E. Yudina ◽  
Nadezhda A. Mazerkina ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Metabolic Disorders ◽  
Gh Deficiency ◽  
Malignant Tumors ◽  
Posterior Cranial Fossa ◽  
Hormone Deficiency ◽  
Lower Sensitivity ◽  
Endocrine Disorders ◽  
Metabolic Complications ◽  
Cranial Fossa

Endocrine disorders are common in patients after treatment for brain tumors in childhood. Growth hormone (GH) deficiency is the most common consequence of cranial irradiation. Objective — to evaluate the prevalence of GH deficieny and metabolic disorders in patients after treatment for malignant tumors of the posterior cranial fossa (MT PCF) in childhood. Material and methods. In this study 40 patients (21 men, 19 women) who had undergone treatment for MT PCF were assessed. Patients underwent surgery, chemotherapy and craniospinal irradiation (CSI) in a dose of 34.9±1.6 Gy with a boost to the PCF 51.3±9.2 Gy. Age at the time of the survey — 19.8±3.05 years; age at the time of treatment — 10.9±3.4 years; follow-up — 7.2±4.2 years. Patient’s anthropometric and laboratory parameters were measured, GH failure was diagnosed by two tests – insulin tolerance test (ITT) and glucagon stimulation test (GST). Results. According to ITT GH deficiency was observed in 82.1% and according to GST in 60.0% of patients. When comparing two tests GST showed 100% specificity, but lower sensitivity (72.2%). Manifestation of GH deficiency depends on the age at the time of treatment (p=0.002). There is significant correlation between age at the time of treatment and SDS of final height (r=0.632; p<0.001). We found a significant correlation between age at the time of treatment and BMI (r=–0,327; p=0.04). Dyslipidemia occurred in 50% of cases. Insulin resistance was recorded in 16.7% of patients. We found significant correlation between the HOMA-IR and BMI (r=0.336; p=0.034). Conclusions. In patients after treatment for MT PCF in childhood GH deficiency and metabolic disorders is highly prevalent. This group of patients should be monitored by endocrinologist for timely detection and treatment of GH deficiency and metabolic complications.

scholarly journals Non-alcoholic steatohepatitis in patients with endocrine pathology. Review

2021 ◽  
pp. 82-93
Author(s):  
S. M. Tkach ◽  
Т. L. Cheverda
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Hormone Deficiency ◽  
Endocrine Disorders ◽  
Male Hypogonadism ◽  
Pathophysiological Mechanism ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Intestinal Dysbiosis ◽  
Obstructive Sleep

Non-alcoholic steatohepatitis (NASH) is a subtype of non-alcoholic fatty liver disease (NAFLD), which in the absence of treatment can progress to the development of cirrhosis and hepatocellular carcinoma, as well as to increased mortality associated with these diseases. The main risk factors for the development of NAFLD and NASH are the presence of insulin resistance and obesity. Quite often NAFLD and NASH are associated with so-called extrahepatic manifestations, such as obstructive sleep apnea, hypertension, dyslipidemia, intestinal dysbiosis, genetic predisposition, sedentary lifestyle and consumption of certain foods. However, NAFLD and NASH are also associated with some endocrine diseases and conditions, including type 2 diabetes, polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or excess, hypercortisolism, vitamin D or prolactin deficiency. In many of these diseases, the key pathophysiological mechanism is insulin resistance. This review considers the putative pathophysiological mechanisms that play an important pathogenetic role in the development of NASH in these endocrine disorders.Unfortunately, our understanding of the pathophysiology of NAFLD in various endocrinopathies is far from complete. In addition, the natural course of NAFLD due to endocrine disorders compared to the course and consequences of “primary” NAFLD is still poorly understood. Therefore, in the coming years, further research into the pathophysiology and clinical features of NASH will be important to better understand the relationship between different endocrinopathies and NAFLD, which will help improve the treatment of this pathology.

Acute Obstructive Sleep Apnea as a Complication of Sphincter Pharyngoplasty

1996 ◽  
Vol 33 (3) ◽  
pp. 183-189 ◽  
Author(s):  
Peter D. Witt ◽  
Jeffrey L. Marsh ◽  
Harlan R. Muntz ◽  
Lynn Marty-Grames ◽  
Greg P. Watchmaker
Keyword(s):  
Speech Intelligibility ◽  
Perioperative Complications ◽  
Genetic Disorder ◽  
Upper Airway ◽  
Medical Problems ◽  
Noninvasive Treatment ◽  
Feeding Difficulties ◽  
Obstructive Sleep ◽  
History Of ◽  
Sphincter Pharyngoplasty

This report describes postoperative airway compromise following sphincter pharyngoplasty (SP) for treatment of post-palatoplasty velopharyngeal dysfunction. A retrospective review of 58 SPs performed for post-palatoplasty velopharyngeal dysfunction, on 30 male, and 28 female patients, over a 5-year study period was undertaken at a tertiary referral academic institution (Washington University School of Medicine), at the St. Louis Children's Hospital, Cleft Palate and Craniofacial Deformities Institute. Eight patients were identified who had the following inclusion criteria: overt perioperative and/or postoperative airway dysfunction, identifiable syndromes, or microretrognathia. Items reviewed were patient demographic factors, associated medical problems, genetics evaluations, nasendoscopic characteristics of velopharyngeal closure, anesthetic evaluation of the patients, and the incidence and severity of perioperative complications. Particular attention was paid to factors contributing to the airway obstruction. Of the eight subjects with perioperative and/or postoperative upper airway dysfunction following SP, five patients had Pierre Robin sequence/micrognathia, while three patients had a history of perinatal respiratory and/or feeding difficulties without micrognathia or an identified genetic disorder. All but two episodes of airway dysfunction resolved within 3 days postoperatively. These patients were discharged home with apnea monitors; both were readmitted with recurrent airway dysfunction. Continuous positive airway pressure (CPAP) was utilized successfully in all instances, and no patients required take-down of the SP to relieve airway dysfunction. CPAP is an effective, noninvasive treatment strategy for management of iatrogenically induced apnea following SP, without sacrificing the surgical benefit of improved speech intelligibility.

scholarly journals Effects of Transcranial Direct Current Stimulation (tDCS) on Go/NoGo Performance Using Food and Non-Food Stimuli in Patients with Prader–Willi Syndrome

2021 ◽  
Vol 11 (2) ◽  
pp. 250
Author(s):  
Albert B. Poje ◽  
Ann Manzardo ◽  
Kathleen M. Gustafson ◽  
Ke Liao ◽  
Laura E. Martin ◽  
...  
Keyword(s):  
Direct Current ◽  
Behavioral Problems ◽  
Transcranial Direct Current Stimulation ◽  
Genetic Disorder ◽  
Event Related Potentials ◽  
Prader Willi Syndrome ◽  
Feeding Difficulties ◽  
Direct Current Stimulation ◽  
Positive Effects ◽  
Related Potentials

Prader–Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by multiple system involvement with hypotonia, poor suck with feeding difficulties, growth and other hormone deficiencies, intellectual disability, and behavioral problems with childhood onset of hyperphagia resulting in obesity, if not externally controlled. Transcranial direct current stimulation (tDCS) has been increasingly shown to modulate cognitive and behavioral processes in children and adults, including food-intake behaviors in patients with PWS. This study further reports the positive effects of brief tDCS sessions on Go/NoGo task performance involving food and non-food stimuli images, alterations in N2 brain amplitude, and genetic subgroup differences (maternal disomy 15, UPD; 15q11-q13 deletion, DEL) before and after tDCS as assessed by event-related potentials (ERPs) in 10 adults with PWS. The results indicate a group effect on baseline NoGo N2 amplitude in PWS patients with DEL vs UPD (p =0.046) and a decrease in NoGo N2 amplitude following tDCS (p = 0.031). Our tDCS approach also demonstrated a trend towards decreased response time. Collectively, these results replicate and expand prior work highlighting neurophysiological differences in patients with PWS according to genetic subtype and demonstrate the feasibility in examining neuromodulatory effects of tDCS on information processing in this patient population to stimulate additional research and treatment.

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