Treatment Of Prader-Willi Syndrome Research Articles

POI score application at start of GH treatment in Prader-Willi syndrome

POI score application at start of GH treatment in Prader-Willi syndrome

Topiramate in the treatment of Prader-Willi syndrome: A case report.

Prader-Willi syndrome (PWS), a neurologic disorder caused by a mutation of chromosome 15, is characterized by such symptoms as hypotonia, hypogonadism, hyperphagia, cognitive impairment, and difficult behaviors. One of the most concerning symptoms is hyperphagia, which can lead to uncontrolled obesity. Obesity is a major cause of increased morbidity and mortality in patients with PWS; however, diagnosing PWS early in life improves the prognosis. An 11-year-old African American boy with a past medical history significant for PWS, attention deficit/hyperactivity disorder, oppositional defiant disorder, obesity, and asthma was admitted after he became violent and destructive at his foster home while trying to get food. The patient had a 28-day stay on the children's crisis intervention unit where quetiapine was discontinued and he was maintained on clonidine 0.1 mg 3 times daily, hydroxyzine 25 mg in the morning and 50 mg at bedtime, montelukast 5 mg daily and titrated on methylphenidate 10 mg in the morning and 5 mg in the afternoon, topiramate 100 mg twice daily, and aripiprazole 10 mg twice daily. The patient displayed improved behavior control and less food-related aggression; he denied any side effects of medications. This case demonstrates the positive effects of topiramate for reducing aggression and demand for food in a child with PWS most likely due to an increase in satiety. It is hard to definitively attribute the positive response directly to topiramate. Further research should be conducted to determine if topiramate is an effective treatment option in these individuals.

Treatment of Prader-Willi Syndrome with Recombinant Somatropin: A Review

Treatment of Prader-Willi Syndrome with Recombinant Somatropin: A Review

Application of recombinant human growth hormone in treatment of Prader-Willi syndrome

Prader-Willi syndrome is a rare genetic disorder characterized by hypotonia, poor feeding in infancy, hyperphagia with evolving obesity, hypogonadism, decreased adult height, and cognitive and behavioral disabilities.Recombinant human growth hormone (rhGH) has been used in treating Prader-Willi syndrome, and it has achieved good results.Several aspects still need to be concerned, including evaluation before rhGH treatment, age at treatment initiation, dosing, monitoring of potential side effects, tolerability, endpoint, response evaluation, use of adjunct therapies, and issues of consent. Key words: Prader-Willi syndrome; Recombinant human growth hormone; Insulin-like growth factor-1; Obesity; Metabolic syndrome

Relationship between antipsychotics and weight in patients with Prader-Willi syndrome.

Individuals with Prader-Willi Syndrome (PWS) are at increased risk for developing behavioral and psychiatric disorders, often requiring antipsychotics (APs). Contrary to significant AP-associated weight gain observed in the general population, existing literature suggests weight loss in patients with PWS. To evaluate the relationship between AP use and body mass index (BMI) at admission, change in BMI during inpatient stay, and length of stay (LOS) in patients admitted to an inpatient PWS treatment program. Retrospective case-control study. Hospital-based, inpatient PWS treatment program serving nationally and internationally referred children and adults with PWS. Cases consisted of 52 pediatric patients with PWS who were taking APs at admission and during their stay, 97 adults with PWS who were taking APs at admission and during their stay, and 11 pediatric and adult patients with PWS who were AP naïve at admission and subsequently started an AP during their stay; all cases were matched with patients with PWS who were AP naïve at admission and during their stay by age (yrs), sex, and race-ethnicity (controls). Between- and within-group differences in admission BMI, BMI change from admission to discharge, and LOS were analyzed. Admission BMI was lower (mean±SD 36.8±11.9kg/m(2) vs 46.7±12.5kg/m(2) , p<0.001) and LOS longer (mean±SD 75.9±38.5days vs 57.8±23.2days, p=0.005) for pediatric cases with AP exposure at admission and during their stay compared with matched controls. All groups experienced significant decreases in BMI from admission to discharge (p≤0.001 for all comparisons), except for pediatric cases with AP exposure at admission and during their stay. Cases that were AP naïve at admission and subsequently started an AP during their inpatient stay experienced a significantly smaller decrease in BMI from admission to discharge than matched controls (-3.011 vs -7.288kg/m(2) , p=0.027). No other comparisons between cases and controls were significantly different. On average, patients with PWS who were prescribed APs lost weight during their inpatient stay, but this varied with patient age and duration of AP use.

Diagnosis and treatments of Prader-Willi syndrome: a review of current consensuses

We analyzed international consensuses of experts and clinical recommendations on diagnosis and treatment of Prader-Willi syndrome (PWS): PWS consensus diagnostic criteria (1993); US PWS Association (PWSA-USA) consensus statements on evaluating of breathing abnormalities (2007), osteoporosis (2008), growth hormone treatment in PWS (2000 and 2009); Endocrine society clinical practice guideline on Prevention and treatment of pediatric obesity (2008); the Second Expert Meeting of the Comprehensive Care of Patients with PWS Consensus published as Recommendations for the diagnosis and management of PWS (2008). Historical analysis and comparison of recommendations are presented in this review article. Absence of Russian clinical practice guidelines on PWS patients management makes necessary the detailed study of listed documents.

Prader-Willi syndrome: new possibilities for its treatment in the children

Prader-Willi syndrome (PWS) is a genetic disease characterized by such symptoms as severe hyperphagia leading to marked obesity, growth retardation, peculiar outward appearance, cognitive disorders, behavioural and psyschiatric problems. At present, recombinant growth hormone (rGH) is the sole effective agent for the treatment of PWS; it significantly improves the quality of life of the patients with this pathology. Numerous beneficial effects and possible risks of rGH therapy of PWS are discussed.

Response to growth hormone treatment in Prader–Willi syndrome: Auxological criteria versus genetic diagnosis

The Australian Prader-Willi Syndrome (PWS) database was established to monitor the efficacy and safety of growth hormone (GH) treatment in PWS. This study aims to compare response to GH based on eligibility criteria. Comparative study: 72 children received GH on the basis of short stature or evidence of GH deficiency (pre-2009: PWS-SS) and 94 on a genetic diagnosis (post-2009: PWS-Dx). We report on mandatory patient data for GH prescription: median and standard deviation score (SDS) for height and body mass index (BMI), waist/height ratio, bone age/chronological age ratio and adverse events. Comparisons were made using non-parametric tests. At baseline, the PWS-SS cohort was shorter (height SDS: -2.6 vs. -1.1, P < 0.001), had a lower BMI (0.6 vs. 1.5 SDS, P < 0.05) and greater bone age delay (bone age/chronological age: 0.7 vs. 0.9, P < 0.05) than the PWS-Dx cohort. PWS-SS parents were shorter (mid-parental height SDS: -0.13 vs. 0.28, P < 0.005). Mean change in height over 2 years was 0.9 SDS and in BMI using PWS reference standards -0.3 SDSPWS (n = 106) (year 2, height SDS: PWS-SS = -1.7, PWS-Dx = 0.1; BMI SDSPWS : PWS-SS = -1.0, PWS-Dx = -0.6). The waist/height ratio reduced (PWS-Dx: 0.60 vs. 0.56, P < 0.05) and bone age delay was unchanged over this period. No serious adverse events were reported. The PWS-SS cohort represents a subgroup of the wider PWS-Dx population; however both cohorts improved height SDS with normalisation of height in the PWS-Dx cohort and lowering of BMI relative to PWS standards supporting the efficacy of treatment under the current Australian GH programme.

Effects of growth hormone treatment in adults with Prader–Willi syndrome

ObjectiveSince limited data exist on adults with Prader–Willi syndrome (PWS) and growth hormone (GH) treatment, we report our experience on the effects of treatment for one year on body composition, physical activity, strength and energy expenditure, diet, general chemistry and endocrine data with quality of life measures. DesignWe studied 11 adults with PWS (6F:5M; average age=32yrs) over a 2year period with GH treatment during the first year only. Electrolytes, IGF-I, glucose, thyroid, insulin, lipids, body composition, physical activity and strength, diet, energy expenditure and quality of life data were collected and analyzed statistically using linear modeling at baseline, at 12months following GH therapy and at 24months after treatment cessation for 12months. ResultsTotal lean muscle mass was significantly increased (p<0.05) during GH treatment along with moderate-vigorous physical activity and plasma IGF-I and HDL levels, but returned to near baseline after treatment. Percent body fat decreased during the 12months of GH treatment but increased after treatment. ConclusionsPreviously reported beneficial effects of GH treatment in children with PWS were found in our adults regarding body composition, physical activity and plasma HDL and IGF-I levels. Several beneficial effects diminished to near baseline after cessation of GH treatment for 12months supporting the continuation of treatment in PWS into adulthood and possibly adults not previously treated during childhood.

An Unexpected Function of the Prader-Willi Syndrome Imprinting Center in Maternal Imprinting in Mice

Genomic imprinting is a phenomenon that some genes are expressed differentially according to the parent of origin. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurobehavioral disorders caused by deficiency of imprinted gene expression from paternal and maternal chromosome 15q11–q13, respectively. Imprinted genes at the PWS/AS domain are regulated through a bipartite imprinting center, the PWS-IC and AS-IC. The PWS-IC activates paternal-specific gene expression and is responsible for the paternal imprint, whereas the AS-IC functions in the maternal imprint by allele-specific repression of the PWS-IC to prevent the paternal imprinting program. Although mouse chromosome 7C has a conserved PWS/AS imprinted domain, the mouse equivalent of the human AS-IC element has not yet been identified. Here, we suggest another dimension that the PWS-IC also functions in maternal imprinting by negatively regulating the paternally expressed imprinted genes in mice, in contrast to its known function as a positive regulator for paternal-specific gene expression. Using a mouse model carrying a 4.8-kb deletion at the PWS-IC, we demonstrated that maternal transmission of the PWS-IC deletion resulted in a maternal imprinting defect with activation of the paternally expressed imprinted genes and decreased expression of the maternally expressed imprinted gene on the maternal chromosome, accompanied by alteration of the maternal epigenotype toward a paternal state spread over the PWS/AS domain. The functional significance of this acquired paternal pattern of gene expression was demonstrated by the ability to complement PWS phenotypes by maternal inheritance of the PWS-IC deletion, which is in stark contrast to paternal inheritance of the PWS-IC deletion that resulted in the PWS phenotypes. Importantly, low levels of expression of the paternally expressed imprinted genes are sufficient to rescue postnatal lethality and growth retardation in two PWS mouse models. These findings open the opportunity for a novel approach to the treatment of PWS.

Issues in Infants with Prader-Will Syndrome: Special Review on Early Dietary Intervention and Early Use of Growth Hormone

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features consist of neonatal hypotonia, distinctive facial features, delayed overall development with mental deficiency, behavioral abnormalities, poor growth in infancy followed by overeating with severe obesity, short stature, and hypogonadism. Recently, patients with PWS have been diagnosed at an earlier age, especially in the neonatal period. In addition, early interventions such as commencement of growth hormone therapy and dietary programs, have received attention in PWS treatment. Since early diagnosis is now possible based on both clinical symptoms and signs and on molecular genetic criteria, early dietary intervention and early growth hormone therapy during the first two years may improve neurodevelopment, increase muscle mass, and reduce obesity. Our aim in this review is to document the characteristics of infants with PWS and to provide a recent update regarding early management.Key Words: Prader-Willi syndrome; Growth hormone; Obesity; Hyperphagia; Infant

Metabolic syndrome in children with Prader–Willi syndrome: The effect of obesity

Background and aims Prader–Willi syndrome (PWS), the most frequent syndromic obesity, is associated with elevated morbidity and mortality in pediatric and adult ages. In PWS, the presence of metabolic syndrome (MS) has not yet been established. The aim of the study was to estimate the frequency of MS and its components in pediatric subjects according to obesity status. Methods and results A cross-sectional study was performed in 109 PWS children aged 2–18 years (50 obese and 59 non-obese) and in 96 simple obese controls matched for age, gender, and also for BMI with obese PWS. Obesity was defined when SDS-BMI was >2. Non-obese PWS showed significantly lower frequency of hypertension (12%) than obese PWS (32%) and obese controls (35%)( p = 0.003). The same was observed for low HDL-cholesterol (3% vs 18% and 24%, p = 0.001) and high triglycerides (7% vs 23% and 16%, p = 0.026). Frequency of altered glucose metabolism was not different among groups (2% vs 10% and 5%), but type 2 diabetes (four cases) was present only in obese PWS. Non-obese PWS showed lower insulin and HOMA-index respect to obese PWS and obese controls ( p ≤ 0.017). Overall MS frequency in PWS was 7.3%. None of the non-obese PWS showed MS compared with 16% of obese PWS and controls ( p < 0.001). When obesity was excluded from the analysis, a significantly lower frequency for clustering of ≥2 factors was still found in non-obese PWS ( p = 0.035). Conclusion Non-obese PWS showed low frequency of MS and its components, while that observed in obese PWS was very close to those of obese controls, suggesting the crucial role of obesity status. Prevention of obesity onset remains the most important goal of PWS treatment. Early identification of MS could be helpful to improve morbidity and mortality in such patients.

Uso de hormônio de crescimento na síndrome de Prader-Willi

Prader-Willi syndrome (PWS), with a prevalence of 60:1.000.000, results from the loss of paternal chromosome 15, being 56% due to deletion, 24% due to uniparental maternal disomy, and 18% from methylation, an epigenetic phenomenon. The clinical picture begins with extreme muscular hypotonia, which makes it difficult to feed the child in the first year. As the hypotonia improves, usually in the first two years, around the 4th year of life, an insatiable appetite leads these children to an extreme obesity, with alveolar hypoventilation which endangers their lives. So, paradoxically, PWS threatens the lives of the patients, through inanition in a first phase and, afterwards, through excessive weight gain. The use of growth hormone (hrGH) in these children has a primary goal to change the body composition and improve the physical activity and the quality of life. On the other hand, many PWS patients are indeed GH deficient, and an improvement in the height SDS occurs with treatment. We have to be careful, however. When starting a PWS treatment with a patient on hrGH, a careful evaluation of sleep apnoea (polysomnography) as well as a careful examination of the airways is extremely mandatory, since the treatment may compromise the respiratory pattern of some patients.

Sleep-Related Breathing Disorders in Prepubertal Children with Prader-Willi Syndrome and Effects of Growth Hormone Treatment

Recently, several cases of sudden death in GH-treated and non-GH-treated, mainly young Prader-Willi syndrome (PWS), patients were reported. GH treatment in PWS results in a remarkable growth response and an improvement of body composition and muscle strength. Data concerning effects on respiratory parameters, are however, limited. The objective of the study was to evaluate effects of GH on respiratory parameters in prepubertal PWS children. Polysomnography was performed before GH in 53 children and repeated after 6 months of GH treatment in 35 of them. Fifty-three prepubertal PWS children (30 boys), with median (interquartile range) age of 5.4 (2.1-7.2) yr and body mass index of +1.0 sd score (-0.1-1.7). Intervention included treatment with GH 1 mg/m2.d. Apnea hypopnea index (AHI) was 5.1 per hour (2.8-8.7) (normal 0-1 per hour). Of these, 2.8 per hour (1.5-5.4) were central apneas and the rest mainly hypopneas. Duration of apneas was 15.0 sec (13.0-28.0). AHI did not correlate with age and body mass index, but central apneas decreased with age (r = -0.34, P = 0.01). During 6 months of GH treatment, AHI did not significantly change from 4.8 (2.6-7.9) at baseline to 4.0 (2.7-6.2; P = 0.36). One patient died unexpectedly during a mild upper respiratory tract infection, although he had a nearly normal polysomnography. PWS children have a high AHI, mainly due to central apneas. Six months of GH treatment does not aggravate the sleep-related breathing disorders in young PWS children. Our study also shows that monitoring during upper respiratory tract infection in PWS children should be considered.

Advances in diagnosis and treatment of Prader-Willi syndrome

Advances in diagnosis and treatment of Prader-Willi syndrome

Prader-Willi Syndrome

After completing this article, readers should be able to: 1. Recognize Prader-Willi syndrome in the neonate. 2. Recognize the hallmarks of disorders due to imprinted genes. 3. Interpret the results of diagnostic testing. 4. Initiate appropriate management to avoid long-term sequelae of massive obesity. 5. Explain the risks and benefits of growth hormone treatment in Prader-Willi syndrome. Prader-Willi syndrome (PWS) is one of the better known genetic syndromes, mostly because of the striking phenotype in older children of massive obesity, hyperphagia, and severe behavior problems, often involving food. Clinicians have recognized for some time that early diagnosis, during the equally striking neonatal hypotonic phase of the disorder, allows for a head start in the management and the avoidance of many of the eating and behavior problems that occur in unmanaged disease. Neonatologists and pediatric neurologists have greatly developed their skills in diagnosing PWS, leading to substantial improvements in the lives of affected children and their families. This is a true success story. This review describes both the neonatal and the later phenotype of PWS, examines the differential diagnosis, discusses current therapy for the disorder, examines the molecular and biologic bases for the disorder, and reviews the tests used to confirm the diagnosis. PWS initially was described in 1956 in children who had short stature, obesity, and mental retardation. Later, it became the first recognized disorder caused by a microdeletion of a chromosome and one of the first examples of a disorder of genomic imprinting. The incidence of PWS is about 1 in 10,000 to 15,000 live births, with no particular geographic or ethnic predilection. Most cases occur sporadically, although rare cases due to primary defects of the imprinting mechanism or resulting from familial translocations involving chromosome 15 may recur. The clinical phenotype of PWS has two distinct phases: the “neonatal hypotonia” phase and the later …

Body composition studies in Prader-Willi syndrome: effects of growth hormone therapy.

Prader-Willi Syndrome (PWS) is characterized by infantile failure to thrive, progressive childhood obesity, hypotonia, hypogonadism, mental retardation and phenotypic abnormalities including short stature. Abnormalities of chromosome 15 can now be identified in virtually all cases1. The pathogenesis of PWS is not known, although the phenotype suggests that there may be an abnormality in substrate utilization leading to an absolute deficit of lean mass and increased fat mass. Hypothalamic and pituitary abnormalities have also been postulated2,3. However, studies of body composition, nutrient utilization, and hormone status in PWS are limited. We report initial results from a detailed investigation of body composition and growth hormone (GH) treatment in PWS.

Pituitary Evaluation and Growth Hormone Treatment in Prader-Willi Syndrome

Pituitary Evaluation and Growth Hormone Treatment in Prader-Willi Syndrome

Interdisciplinary case management: A model for intervention

Interdisciplinary case management is required when clients present problems that do not fall within the purview of any one discipline. The interdisciplinary approach entails the participation of professional and support staff, along with the client and his/her family, in diagnosis, individual program planning, implementation, and evaluation. For example, interdisciplinary case management for a patient with Prader-Willi syndrome (PWS) results in cost-effective, efficacious treatment. Because of the diversity of symptoms, the treatment of Prader-Willi syndrome must incorporate knowledge and skills from a variety of areas. A model for the interdisciplinary case management of PWS is presented. The model is problem focused and emphasizes goals formulated and acted upon by the disciplines represented on the client's treatment team. Communication and coordination of efforts are central to the utility of the model. Additional benefits of interdisciplinary case management include the opportunity for ongoing education and role expansion of team members. J Am Diet Assoc 88:33, 1988.