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Prader–Willi syndrome (PWS) is a genetic condition caused by a lack of paternally‐expressed imprinted genes at chromosome 15q11.2‐q13 and characterized by hyperphagia, behavioral challenges, and variable intellectual disability. Once a PWS diagnosis is established, sharing diagnosis information with an affected child can be challenging due to its early age of onset and diverse phenotype. This mixed‐methods study aimed to evaluate how parents and guardians have shared a PWS diagnosis with their child and examine the motivating and influencing factors behind their disclosure. Parents and guardians of children with PWS aged at least 5 years completed a survey, and a select group completed an interview. A total of 51 surveys and 15 interviews were completed, with the majority of participants (n = 46; 90%) having shared at least some diagnosis information with their child. Parents and guardians were more likely to disclose if they self‐reported a higher level of knowledge about PWS (p = 0.004) and if their child is currently older (p = 0.02) and/or has at least one sibling (p = 0.046). Interview analysis revealed 15 themes and 10 subthemes that illustrated parents' motivations, methods, and experiences with disclosure. This research provides information for others considering disclosure of PWS or another rare diagnosis with their child. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is the most common genetic syndrome with obesity and results from loss of expression of paternally inherited genes on chromosome 15q11‐q13 by a variety of mechanisms which include large deletions (70%–75%), maternal uniparental disomy (UPD) (20%–30%), and imprinting defects (2%–5%) or balanced translocations. Individuals often have a characteristic behavior disorder with mild intellectual disability, infantile hypotonia associated with poor sucking, short stature, and obesity. PWS is characterized by hypothalamic–pituitary axis dysfunction with growth hormone (GH) deficiency, hypogonadism, and several other hormonal deficiencies resulting in short stature, centrally driven excessive appetite (hyperphagia), central obesity, cryptorchidism, and decreased lean body mass. In this study, we determined and sought differences in the incidence of thyroid abnormalities among the common genetic subtypes in a cohort of 52 subjects with PWS because there was limited literature available. We also sought the effects of growth hormone (GH) treatment on the thyroid profile. Fifty‐two subjects with a genetically confirmed diagnosis of PWS were included in this study at the University of California, Irvine. Blood samples for baseline thyroxine stimulating hormone (TSH) and free thyroxine (fT4) levels were obtained in the morning after an overnight fast for 8–12 h. Statistical analyses were performed with SPSS (SPSS Inc., 21.0). Mean values were analyzed by one‐way ANOVA, and student's t‐test and statistical significance were set at p < 0.05. The subjects included 26 males and 26 females with an age range of 3–38 years. There were 29 subjects with chromosome 15q11‐q13 deletions and 23 with UPD; 28 were GH treated currently or in the past, and 24 never received GH. There was no significant difference in age or body mass index (BMI) (kg/m2) between GH‐treated versus non‐GH‐treated groups. BMI was higher in the deletion group compared to the UPD group (p = 0.05). We identified two individuals who were clinically diagnosed and treated for hypothyroidism, one of whom was on GH supplements. We identified two additional individuals with subclinical hypothyroidism who were not on GH treatment, giving a frequency of 7.6% (4/52) in this cohort of patients. We did not find significant differences in thyroid function (TSH) in the deletion versus UPD groups. We found significant differences in thyroid function, however, between GH‐treated and non‐GH‐treated groups. The mean TSH was lower (2.25 ± 1.17 uIU/M, range 0.03–4.92 uIU/M versus 2.80 ± 1.44 uIU/M, range 0.55–5.33 uIU/M respectively, p = 0.046), and the free T4 levels were significantly higher (1.13 ± 0.70 and 1.03 ± 0.11 ng/dL, respectively, p = 0.05) in the GH‐treated individuals compared to non‐GH‐treated individuals. In this cohort of subjects with PWS, we identified two previously diagnosed individuals with hypothyroidism and two individuals with subclinical hypothyroidism (4/52, 7.6%), three of whom were not receiving GH treatment. We did not find any significant differences in thyroid function between molecular subtypes; however, we found that euthyroid status (lower TSH levels and higher free T4 levels) was significantly higher in individuals who were treated with GH compared to the untreated group. We recommend that individuals with PWS should be screened regularly for thyroid deficiency and start treatment early with GH in view of the potentially lower incidence of thyroid deficiency. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a rare genetic disorder caused by the loss of paternal genes on chromosome 15. The Aberrant Behavior Checklist (ABC) is a standardized rating scale for assessing problematic behaviors in persons with developmental disabilities. Our study aims to describe ABC scores in youth with PWS and track their change over time. The analysis included 69 patients. Mean ABC scores were compared in four age groups (5–8, 9–12, 13–16, and 17–22 years). A statistically significant difference was found only in the Irritability subscale, with lower scores in the 5–8 age group compared to the 9–12 age group. For change over time, scores for Irritability, Lethargy, Stereotypic Behavior, Hyperactivity subscales, and Total score were likely to decrease after age 12. Irritability subscale scores of males were predicted to increase more than those of females between ages of 5 and 12. The Lethargy score in the nondeletion group had a greater reduction than the deletion group in the 12–20 year range. This study highlights the need for systematic collection and characterization of behavioral data given the burden of maladaptive behaviors that often persist for a lifetime. [ABSTRACT FROM AUTHOR]

Feeding difficulties, aspiration, and failure to thrive in infancy are commonly seen in patients with Prader–Willi Syndrome (PWS) and attributed to hypotonia. Patients with PWS and laryngeal clefts were identified by review of medical records at three tertiary care children's hospitals between 2017 and 2022. We present three patients with PWS with feeding difficulties who were also found to have laryngeal clefts which likely contributed to their feeding difficulties. Additional factors such as airway anomalies should be considered in patients with PWS, especially when swallowing dysfunction, dysphagia, or abnormal swallow evaluations are present. [ABSTRACT FROM AUTHOR]

Guidance on indications for, and types of, feeding tubes recommended in Prader‐Willi syndrome (PWS) is needed. A Global PWS Registry survey was developed to investigate nasogastric (NG) and gastrostomy (G) tube use and associated complications. Of 346 participants, 242 (69.9%) had NG‐tubes, 17 (4.9%) had G‐tubes, and 87 (25.1%) had both NG‐ and G‐tubes. Primary indication for placement was "feeding difficulties and/or poor weight gain" for both NG‐ (90.2%) and G‐tubes (71.2%), while "aspiration/breathing difficulties" was the procedural indication for 6.4% of NG‐tubes and 23.1% of G‐tubes. NG‐tubes were generally removed by age 6 months (NG Only: 82.9%; NG/G: 98.8%), while G‐tubes were often removed by age 2 years (G Only: 85.7%; NG/G: 70.5%). The severe complication rate from G‐tubes was 31.7% and from NG‐tubes was 1.2%. Overall, caregivers indicated the presence of an NG‐ or G‐tube had a positive effect on quality of life. Feeding difficulties in PWS are largely managed by NG‐tube alone. The severe complication rate from G‐tubes was about 25 times higher than from NG‐tubes; yet, G‐tube placement rates have generally increased. G‐tube placement puts individuals with PWS at risk for anesthesia and surgery‐related complications and should be considered judiciously by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is a genomic imprinting disorder characterized by infantile hypotonia with a poor suck and failure to thrive, hypogenitalism/hypogonadism, behavior and cognitive problems, hormone deficiencies, hyperphagia, and obesity. The Stanford Binet and Wechsler (WAIS-R; WISC-III) intelligence (IQ) tests were administered on 103 individuals with PWS from two separate cohorts [University of California, Irvine (UCI) (N = 56) and Vanderbilt University (N = 47)] and clinical information obtained including growth hormone (GH) treatment, PWS molecular classes, weight and height. Significantly higher IQ scores (p

Prader-Willi syndrome (PWS) is generally due to sporadic paternal deletions of the chromosome 15q11-q13 region followed by maternal disomy 15. Advanced maternal age is more commonly seen in those with maternal disomy 15. Environmental factors (e.g., drug use, occupational chemical exposure, infectious agents, and irradiation) could account for chromosome changes. Previous evidence of differences in male and female gametogenesis could suggest an environmental role in the causation of the paternal 15q11-q13 deletion seen in PWS. Certain occupations such as hydrocarbon-exposing occupations (e.g., landscaping, farming, and painting) and viral exposure (e.g., human coronavirus 229E causing upper respiratory infections in adults with an incorporation site in the human genome at chromosome 15q11) can be seasonal in nature and contribute to chromosome damage. To assess, we reviewed birth seasonality data in a large cohort of individuals with PWS recruited nationally (N = 355) but no significant differences were seen by month between those with the 15q11-q13 deletion compared with maternal disomy 15 when analyzing quarterly seasonal patterns. Although early evidence supported birth seasonality differences in PWS, a larger number of individuals in our recent study using advanced genetic testing methods did not find this observation.

Prader-Willi syndrome (PWS), is a complex genetic disease affecting 1/15,000 individuals, characterized by lack of expression of genes on the paternal chromosome 15q11-q13 region. Clinical features include central hypotonia, poor suck, learning and behavior problems, growth hormone deficiency with short stature, hyperphagia, and morbid obesity. Despite significant advances in genetic testing, the mean age for diagnosis in PWS continues to lag behind. Our goal was to perform a pilot feasibility study to confirm the diagnosis utilizing different genetic technologies in a cohort of 34 individuals with genetically confirmed PWS and 16 healthy controls from blood samples spotted and stored on newborn screening (NBS) filter paper cards. DNA was isolated from NBS cards, and PWS testing performed using DNA methylation-specific PCR (mPCR) and the methylation specific-multiplex ligation dependent probe amplification (MS-MLPA) chromosome 15 probe kit followed by DNA fragment analysis for methylation and copy number status. DNA extraction was successful in 30 of 34 PWS patients and 16 controls. PWS methylation testing was able to correctly identify all PWS patients and MS-MLPA was able to differentiate between 15q11-q13 deletion and non-deletion status and correctly identify deletion subtype (i.e., larger Type I or smaller Type II). mPCR can be used to diagnose PWS and MS-MLPA testing to determine both methylation status as well as the type of deletion or non-deletion status from DNA extracted from NBS filter paper. We propose that PWS testing in newborns is possible and could be included in the Recommended Uniform Screening Panel after establishing a validated cost-effective method.

Prader-Willi syndrome (PWS) is caused by a deficiency of imprinted genes in the 15q11-q13 region and is characterized by prenatal onset of hypotonia, poor feeding, childhood-onset obesity, hyperphagia, short stature, facial dysmorphism, intellectual disability, and behavioral problems. We studied perinatal factors in a cohort of 64 people with PWS resulting from paternal deletion of 15q11-q13 and maternal uniparental disomy (UPD) for chromosome 15. We recruited 34 individuals with deletion and 30 with UPD. We compared the frequency of multiple prenatal and neonatal factors with the general population as well as between the two genetic subtypes. Of the 64 individuals with PWS, fetal movements were decreased in 82.8%, 31.7% were born prematurely, 42.1% by Cesarean section, and 35.9% required oxytocin induction. Apgar scores were low in 34.6%, 96.8% had feeding difficulty, 50% needed tube feeding, and 6.2% subsequently had gastrostomy tube placement. On comparing findings in the deletion versus the UPD groups, we did not find many significant differences. We, however, found a higher maternal age, and also later age at diagnosis in the UPD versus the deletion group. PWS subjects have higher rates of perinatal complications, especially Cesarean section rate, hypotonia, and low Apgar scores compared to the general population. We did not find many differences between the genetic subtypes, except for later age of diagnosis of the UPD 15 group suggesting a milder phenotype. We also found that the mothers in the UPD were older, supporting the hypothesis that UPD results from nondisjunction associated trisomy rescue.

We describe the National Institutes of Health rare disease consortium for Prader-Willi syndrome (PWS) developed to address concerns regarding medical care, diagnosis, growth and development, awareness, and natural history. PWS results from errors in genomic imprinting leading to loss of paternally expressed genes due to 15q11-q13 deletion, maternal disomy 15 or imprinting defects. The 8 year study was conducted at four national sites on individuals with genetically confirmed PWS and early-onset morbid obesity (EMO) with data accumulated to gain a better understanding of the natural history, cause and treatment of PWS. Enrollment of 355 subjects with PWS and 36 subjects with EMO began in September 2006 with study completion in July 2014. Clinical, genetic, cognitive, behavior, and natural history data were systematically collected along with PWS genetic subtypes, pregnancy and birth history, mortality, obesity, and cognitive status with study details as important endpoints in both subject groups. Of the 355 individuals with PWS, 217 (61%) had the 15q11-q13 deletion, 127 (36%) had maternal disomy 15, and 11 (3%) had imprinting defects. Six deaths were reported in our PWS cohort with 598 cumulative years of study exposure and one death in the EMO group with 42 years of exposure. To our knowledge, this description of a longitudinal study in PWS represents the largest and most comprehensive cohort useful for investigators in planning comparable studies in other rare disorders. Ongoing studies utilizing this database should have a direct impact on care and services, diagnosis, treatment, genotype-phenotype correlations, and clinical outcomes in PWS.

Prader–Willi syndrome is a complex neurodevelopmental genetic imprinting disorder with severe congenital hypotonia, failure to thrive with learning and behavioral problems, and hyperphagia with obesity developing in early childhood. Those with the typical 15q11–q13 Type I deletion compared with the smaller Type II deletion have more severe neurobehavioral problems and differ by the absence of four genes in the 15q11.2 BP1–BP2 region. Two of the genes encode magnesium transporters supporting brain and neurological function and we report on magnesium levels in the two deletion groups of PWS participants. We measured baseline plasma magnesium and analyzed data from a PWS cohort with and without the Type I or Type II deletion. Significantly lower plasma magnesium levels were found in PWS participants with the larger Type I deletion and more so with females with Type I deletion compared with females having the Type II deletion, although magnesium levels remained within normal range in both subgroups. Those with PWS and the larger 15q11–q13 Type I deletion were more clinically affected than those with the smaller Type II deletion. Two of the four genes missing in those with the larger deletion code for magnesium transporters and may impact magnesium levels. Our study showed lower magnesium levels in those with the larger deletion which could contribute to neurobehavioral differences seen in the two separate 15q11‐q13 deletion subtypes and in addition affect both glucose and insulin metabolism impacting comorbidities but will require more research. [ABSTRACT FROM AUTHOR]

Prader–Willi Syndrome (PWS) is a multi‐system genetic disorder characterized by hyperphagia and a range of medical complications. While register and cohort studies have explored the natural course of the syndrome, there is little nationally‐representative data. In this study the National Inpatient Sample, a de‐identified all‐payors database of acute care hospital discharges in the United States, was queried for patients discharged with a diagnosis of PWS in 2019. Hospitalizations involving PWS were compared to hospitalizations without a PWS diagnosis matched based on demographic and hospital factors. In total, 540 hospitalizations (95% CI: 513–567) included a diagnosis of PWS. Median age at time of admission was 22 years, with an interquartile range of 6.3–37.8 years. Respiratory conditions accounted for 110 (20.4%) of primary discharge diagnoses, with infectious conditions for 70 (13.0%) and digestive conditions for 65 (12.0%). Hospitalizations involving PWS were significantly more likely to involve respiratory failure (OR 5.49; 95% CI 3.86–7.80), septicemia (OR 2.80, 95% CI 1.97–3.96), or intestinal obstruction and ileus (OR 6.29; 95% CI 3.70–10.7) compared to matched hospitalizations without PWS. Obesity was diagnosed in 230 PWS hospitalizations (42.6%; OR 3.86, 95% CI 3.17–4.72 relative to non‐PWS hospitalizations). These results point to an ongoing need for the improved diagnosis and treatment of PWS complications, and highlight the importance of specific billing codes for rare diseases to enhance the collection of real world evidence. [ABSTRACT FROM AUTHOR]

Hypogonadism is the most frequent hormonal deficiency in individuals with Prader‐Willi syndrome (PWS). This often necessitates testosterone treatment, but limited data are available to guide testosterone treatment in adult men with PWS. We aimed to evaluate the serum testosterone concentrations and adverse effects of testosterone treatment in individuals with PWS attending a specialist obesity management service. A retrospective audit was undertaken at Austin Health, Melbourne between January 2010 and April 2021. Main outcome measures were testosterone formulation and dose, serum total testosterone concentration, and prevalence of polycythemia and behavioral disturbance. Data were available for eight individuals with median baseline age 19 years (range, 19–42) and BMI 37 kg/m2 (range, 27–71). Six men had obstructive sleep apnea; none were smokers. Baseline testosterone concentration was 1.8 nmol/L (IQR, 1.1–3.3) with hematocrit 0.43. Testosterone formulations were intramuscular testosterone undecanoate (TU) 1000 mg (n = 5), transdermal testosterone gel 50 mg daily (n = 1), and oral TU 80–120 mg daily (n = 2). Median total testosterone concentration was 9.7 nmol/L (IQR, 8.5–14.7). Nine of 25 (36%) hematocrit results in six patients measured >0.50 (range, 0.50–0.56). Intramuscular TU was well tolerated and was the only formulation to achieve serum total testosterone concentrations in the adult male reference range. Worsening behavioral disturbance resulted in treatment discontinuation in one individual. Our experience reinforces the need to regular monitoring of hematocrit in men with PWS treated with testosterone. However, a worsening of behavior problems was uncommon in this series. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder which includes hypothalamic dysfunction, hyperphagia, cognitive and behavioral problems, increased anxiety, and compulsive behaviors. Individuals with PWS have a deficit of oxytocin producing neurons in the paraventricular nucleus of the hypothalamus. Oxytocin plays a role in regulation of feeding behaviors, social interactions, and emotional reactivity, which are all issues that significantly affect the quality of life for individuals with this syndrome. We performed a double-blind, placebo-controlled, crossover study in 24 children with PWS at three academic institutions using 5 days of intranasal oxytocin (IN-OT) or 5 days of intranasal placebo spray, followed by a 4 week washout period, and then patients returned for 5 days of treatment with the alternate source. Questionnaires, including the Aberrant Behavior Checklist, Social Responsiveness Scale, Repetitive Behavior Scale - Revised, and the Hyperphagia Questionnaire, as well as Clinical Global Impression scales were administered. Blood testing for sodium, potassium, and glucose levels on days 2, 4, and 6, and a 24 hr diet recall. All scales factor improvement from Day 3 to Day 6 favored oxytocin over placebo. No single factor showed a statistically significant difference (P

Prader‐Willi Syndrome (PWS) is a rare genetic disorder associated with emotional/behavioral disturbances. These difficulties are well documented in the literature, but the positive attributes of these individuals are not described. Taking a strengths‐based approach, the aim of this study was to describe the emotional/behavioral strengths and difficulties in children and young people with PWS from their parent caregivers' perspectives. Parent caregivers of 52 individuals with PWS aged 4–24 years (median = 12.1 years; including 22 males) completed the parent form of the Developmental Behavior Checklist (DBC‐P), including its original two open‐ended questions regarding positive traits. Prevalences of emotional/behavioral disturbances were comparable to those reported in previous literature: common behaviors of concern across studies being skin‐picking (75%), impulsivity (69%), poor sense of danger (67%), lying (67%), and tantrums (54%). Total DBC‐P scores showed that just over half (n = 28, 54%) had scores indicative of clinically significant behavior problems. However, thematic analysis of caregivers' written comments regarding their children's strengths resolved into three themes: warmth (94%), persistence (41%), and skills (41%). Warmth encompassed friendliness, happiness, and empathy. A strength‐based approach to behavioral difficulties in PWS provides a more balanced view of the children and a more holistic foundation for interventions. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a genetic disorder characterized by hypotonia and poor feeding in infancy which progresses to hyperphagia in early‐mid childhood, as well as developmental delays, a spectrum of behavioral and psychiatric concerns, endocrinopathies, orthopedic issues, and less commonly, seizures, sleep apnea, and narcolepsy with or without cataplexy. This study used data in the Global PWS Registry (N = 893) to explore the onset and severity over time of the neuropsychiatric features reported in individuals with PWS and explored its associations with sleep disorders, seizures, and psychiatric symptoms. Results demonstrate that seizures are more common in the deletion subtype and that narcolepsy and cataplexy are more common in individuals who have sleep‐related seizures. Finally, this work shows that anxiety and compulsive behaviors are persistent features of PWS that may arise early in childhood, and that anxiety is associated with higher frequency of other comorbid psychiatric diagnoses. In conclusion, this study is one of the largest to date characterizing sleep disorders and neuropsychiatric characteristics of individuals with PWS and reports on the novel association between sleep disorders and seizures. This study is also one of the first to offer details on the nature of the progression of these features in individuals with PWS. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed genes in chromosome region 15q11‐13. In addition to typical characteristics such as hyperphagia, PWS is evidenced by a certain behavioral phenotype. Common indicators are repetitive behaviors, temper tantrums, and self‐injurious behaviors such as skin‐ and/or rectal picking. N‐Acetylcysteine (NAC) was previously described as a promising therapeutic option for skin picking in PWS. In this case series, we retrospectively investigated the effect of pharmacotherapy with NAC in 14 individuals with PWS suffering from skin‐ and/or rectal picking. Treatment success was determined using the Clinical Global Impression—Improvement scale (CGI‐I). The Clinical Global Impression—Efficacy index (CGI‐EI) was used to put treatment success and side effects into perspective. Six of fourteen patients, all of which were female, showed improvement in symptoms (dosage 1800–2400 mg/day), whereas six patients did not show any change during treatment. Moreover, two male patients treated for solitary rectal picking showed new onset of skin picking. Across all cases, a CGI‐I of 3 (corresponding to minimal improvement) was seen after 3 months of treatment, with a CGI‐EI of 1.6 (corresponding to moderate efficacy). NAC remains a reasonable therapeutic option in certain cases of skin picking in PWS but provides only limited efficacy compared to previous studies on the topic. There was a higher rate of adverse drug reactions than previously reported. The results particularly suggest caution in future treatment in individuals with solitary rectal picking and reduced efficacy when coadministered with neuroleptics. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a common neurocutaneous disorder characterized by development of pigmentary skin changes, neurogenic tumors, and other manifestations involving multiple organ systems. Penetrance is complete, though expressivity is quite variable even among the family members. Given that NF1 is a common hereditary condition, existence of a second genetic disorder in NF1 patients is not unexpected. During comprehensive evaluations of individuals with NF1, we encountered 11 patients with dual diagnosis who contributed to phenotypic complexity and challenges for long‐term management. Examples include Prader–Willi Syndrome, Autosomal Dominant Polycystic Kidney Disease, Down syndrome, infantile myofibromatosis, Craniosynostosis, cleft lip and palate, 47,XYY, 22q11.2 duplication, 15q13.3 deletion syndrome, and BRCA2‐ and ATM‐ related cancer predisposition syndromes. Presence of dysmorphism, developmental delay, atypical tumors, and family history of other genetic disorders including cancers appears as determinants to consider a second genetic etiology and helps to differentiate from an extreme phenotypic spectrum of NF1. Clinicians should have high index of suspicion to exclude coexisting disorders, as apart from providing comprehensive medical care. This also has potential implications in genetic counseling. Long‐term effects of the synergistic mechanisms leading to phenotypic complexity and patient outcomes are yet to be characterized, with follow‐up needed. [ABSTRACT FROM AUTHOR]

Hyperphagia leading to severe obesity with increased morbidity and mortality is the major manifestation of Prader‐Willi syndrome. Caring for these individuals in a home environment is challenging and stressful for caregivers and families. Residential hostels specifically for PWS adults offer programs of diet, exercise, and vocational opportunities, but long‐term effects of PWS hostel living have not been reported. We studied long‐term changes in body mass index (BMI) for PWS adults living in residential hostels compared with age‐matched controls living with families at home. The study included all 34 individuals (18 men) aged >17 years with genetically confirmed PWS living in residential hostels. BMI was recorded at the time of yearly clinic visits and compared to 23 PWS adults (10 men) living at home. BMI on entering the hostel was 36.3 ± 11.0 kg/m² and decreased to 27.0 ± 5.6 kg/m² (p < 0.001) after 6.9 ± 3.9 years. For 21 residents, a slight rise of BMI to 28.8 kg/m² was observed 5.1 ± 2.5 years after the lowest value was achieved. BMI of 23 PWS adults at home was 36.8 ± 12.7 kg/m² versus 27.9 ± 7.1 kg/m² for hostel residents in the same age range (p = 0.008). From 2008 to 2019, there were five deaths among PWS individuals aged 18–40 years living at home, compared with one death (a 43‐year‐old man) among hostel residents. Adults with PWS living in hostels lose weight, maintain BMI values in a normal to mildly overweight range, and have lower mortality in contrast to individuals in a family home environment. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by lack of the paternal copy of maternally imprinted, paternally expressed genes at the chromosome 15q11‐13 region. In most cases, it is caused by a paternal deletion or a maternal disomy of chromosome 15. Behavioral problems with temper outbursts are common and often combined with physical aggressiveness and self‐injury. They are the most frequent cause for a reduced quality of life in adulthood and represent a serious challenge for the individual and those surrounding the individual in everyday life. Until now, no promising pharmaceutical treatment option has been established, and only a few case reports on treatment with selective serotonin reuptake inhibitors (SSRIs) have been reported. In this case series, we investigated the effect of the SSRI sertraline in 14 individuals with PWS frequently showing severe temper outbursts with aggressiveness and self‐injuries. After 6 months of treatment with sertraline, 13 of 14 patients (92.6%) either no longer displayed temper outbursts or showed a significant decrease in frequency and severity of temper outbursts. In one case, treatment was stopped due to severe sleep abnormalities. We conclude that sertraline is a promising and safe treatment option for severe temper outbursts in patients with PWS. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple endocrine, metabolic, respiratory, cognitive, and behavioral/psychiatric symptoms that may lead to severe emotional strain in their caregivers. In this study, we evaluated parenting stress by the Parenting Stress Index‐short form (PSI/SF) and parent‐reported behavioral symptoms by the Child Behavior Checklist (CBCL/6–18) in families of children with PWS. Sixty‐seven home‐resident PWS patients and their families were recruited in this study. The patients' mean age was 14.9 ± 8.3 years, and 33 (50.8%) were male. High parenting stress was reported by 41.5% families, as determined by high total stress scores of PSI/SF. The patients in high stress families were significantly older than those in low stress families (18.2 ± 8.0 vs. 12.6 ± 7.8 years, p =.007). CBCL/6–18 was used to evaluate the somatic and neuropsychiatric symptoms of PWS patients aged between 6 and 18 in the subgroup of the 35 families. In this subgroup, 37.1% of families reported high parenting stress. High stress families reported a higher T‐score in anxiety/depression, withdrawn behavior, somatic complaints, thought problems, attention problems, and delinquent and aggressive behavior of their children with PWS. After multivariate stepwise logistic regression analysis, the T‐score of somatic complaints was the only factor related to high parenting stress, with an odds ratio of 1.279. Our data demonstrated the high care burden of families with PWS and highlighted the importance of having dedicated medical care for both somatic and neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a prototypic genetic condition related to imprinting. Causative mechanisms include paternal 15q11‐q13 deletion, maternal chromosome 15 uniparental disomy (UPD15), Prader–Willi Syndrome/Angelman Syndrome (PWS/AS) critical region imprinting defects, and complex chromosomal rearrangements. Maternal UPD15‐related PWS poses risks of concomitant autosomal recessive (AR) disorders when the mother carries a pathogenic variant in one of the genes on chromosome 15 associated with autosomal recessive inherited disease. Co‐occurrence of autosomal recessive conditions in the setting of UPD leads to increased complexity of the clinical phenotype, and may delay the diagnosis of PWS. We report a patient with PWS and associated congenital ichthyosis due to maternal UPD15, and a homozygous novel pathogenic variant in ceramide synthase 3 (CERS3). We also review the literature of associated disorders reported in the setting of maternal UPD15‐related PWS and provide a summary of the previously described CERS3 variants. This represents the second case of autosomal recessive congenital ichthyosis (ARCI) in the setting of PWS and UPD15. There needs to be a high index of suspicion of this genetic mechanism when there is unexpected phenotype or evolution of the clinical course in a patient with PWS. [ABSTRACT FROM AUTHOR]

This study examined sensitivity of eye tracking measures to hyperphagia severity in Prader‐Willi syndrome (PWS). Gaze data were collected in 57 children with PWS, age 3–11 years, and 47 typically developing peers at two study sites during free visual exploration of complex stimulus arrays that included images of food, animals, and household objects. Analysis of the number and duration of fixations as well as gaze perseverations revealed that food items are not exceptionally salient for children with PWS. Instead, increased attention to food in the context of other high‐interest items (e.g., animals) was associated with caregiver reports of more severe hyperphagia and more advanced nutritional phase. The study also provided preliminary evidence of possible genetic subtype and sex differences as well as demonstrated that multiple investigators in a wide range of settings can effectively implement the eye tracking protocol. The results indicate that gaze characteristics derived from eye tracking may be a promising objective marker of hyperphagia in PWS for use in research and clinical trials. [ABSTRACT FROM AUTHOR]

It is unclear whether hypothyroidism is present in patients with Prader–Willi syndrome (PWS). This study aimed to clarify the state of the hypothalamic–pituitary–thyroid axis and the effects of growth hormone (GH) treatment on thyroid function in pediatric patients with PWS. We retrospectively evaluated thyroid function in 51 patients with PWS before GH treatment using a thyroid‐releasing hormone (TRH) stimulation test (29 males and 22 females; median age, 22 months). We also evaluated the effect of GH therapy on thyroid function by comparing serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels at baseline, 1 year, and 2 years after GH therapy. TSH, fT4, and fT3 levels were 2.28 μU/ml (interquartile range [IQR]; 1.19–3.61), 1.18 ng/dl (IQR; 1.02–1.24), and 4.02 pg/dl (IQR; 3.54–4.40) at baseline, respectively. In 49 of 51 patients, the TSH response to TRH administration showed a physiologically normal pattern; in two patients (4.0%), the pattern suggested hypothalamic hypothyroidism (delayed and prolonged TSH peak after TRH administration). TSH, fT4, and fT3 levels did not change significantly during 1 or 2 years after GH treatment. The TSH response to TRH showed a normal pattern in most patients, and thyroid function did not change significantly during the 2 years after initiating GH treatment. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) affects 1/15,000–1/30,000 live births and is characterized by lack of expression of paternally inherited genes on 15q11.2‐15q13 caused by paternal deletions, maternal uniparental disomy (UPD), or imprinting defects. Affected individuals have distinct physical features, and growth hormone (GH) deficiency occurs in some individuals with PWS. The aim of this study is to test the hypotheses that (a) individuals with deletions and UPD have different physical and dysmorphic features, (b) individuals treated with GH have different physical and dysmorphic features than those not treated, and (c) GH treatment effects are different for individuals with UPD in comparison to those with deletions. Study participants included 30 individuals with deletions or UPD, who did or did not have GH treatment. Participants' molecular abnormalities were determined by molecular and cytogenetic analysis. Clinical data were obtained by a single dysmorphologist. Individuals with deletions were found to be heavier (p =.001), taller (p =.031), with smaller head circumferences (p =.042) and were more likely to have fair skin and hair than their family members (p =.031,.049, respectively) compared to UPD patients. Females with deletions more commonly had hypoplastic labia minora (p =.009) and clitoris (.030) in comparison to those with UPD. Individuals who received GH in both deletion and UPD groups were taller (p =.004), had larger hands (p =.011) and feet (p =.006) and a trend for a larger head circumference (p =.103). Interestingly, the GH‐treated group also had a lower rate of strabismus (esotropia [p =.017] and exotropia [p =.039]). This study showed statistically significant correlations between phenotype and molecular subtypes and also between phenotype and GH treatment. [ABSTRACT FROM AUTHOR]

Psychosis is a relatively common psychiatric phenomenon seen in patients with Prader–Willi Syndrome (PWS). However, the presentation is atypical and difficult to classify within currently defined affective or psychotic disorders. This distinct presentation may be better understood as a phenomenon called "cycloid psychosis," described as an episodic psychosis with rapid full recovery between episodes. This study retrospectively analyzed the cases of 12 patients with genetically confirmed PWS who presented to an ambulatory psychiatric center for a change in behavior consistent with psychosis. Each case was then assessed for symptoms of cycloid psychosis, bipolar disorder, depression with psychotic features, schizophrenia, and schizoaffective disorder. Out of the 12 patients, 11 (91.7%) met the currently described diagnostic criteria for cycloid psychosis. Of the 12 patients, 7 (58.3%) also met the diagnostic criteria for bipolar disorder, and 1 (8.3%) also met the diagnostic criteria for schizoaffective disorder. None of the patients met the criteria for schizophrenia or depression with psychotic features. The findings in this study suggest that cycloid psychosis and bipolar disorder may both be comorbid with PWS. Psychiatric comorbidities in patients with PWS are atypical and clinicians should be aware of conditions such as cycloid psychosis when managing this vulnerable population. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a multi‐system disorder resulting from a lack of paternal gene expression in the 15q11.2‐q13 region. Using databases compiled through response questionnaires completed by families known to the Prader‐Willi Syndrome Association (USA), this study tested the hypothesis that PWS genetic subtype, BMI, age of diagnosis, clinical symptoms, and growth hormone treatment differ among deceased and living individuals with PWS. Categorical and continuous variables were compared using chi‐square and two‐group t tests, respectively. Deceased individuals had higher rates of clinical features, including increased weight concerns, heart problems, sleep apnea, other respiratory complications, diabetes, osteoporosis, high pain tolerance, and severe skin picking, when compared to living individuals. Meanwhile, living individuals had higher rates of growth hormone use and early puberty. Obesity and subsequent consequences are the primary contributors to increased mortality in PWS. Additional emphasis on areas to decrease mortality is needed. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS, OMIM # 176270) and Down syndrome (DS, OMIM #190685) are neurodevelopmental genetic disorders with higher rates of autism spectrum disorder (ASD). The Aberrant Behavior Checklist (ABC) is a caregiver rating scale that assesses maladaptive behaviors. Overlapping symptoms exist between PWS, DS, and ASD, including maladaptive behaviors. We aimed to evaluate ABC profiles between PWS, DS, and ASD alone (without known genetic syndrome). In addition, we hypothesized PWS and DS with a comorbid ASD positive screen or diagnosis would have similar ABC profiles to ASD alone. ABC data from the following cohorts were analyzed: PWS (Seattle Children's Hospital, n = 28, mean age = 12.8 ± 4.9 years; University of Florida, n = 35, mean age = 9.3 ± 7.1 years), DS (Johns Hopkins, n = 406, mean age = 8.1 ± 2.4 years), and ASD (University of Florida, n = 102, mean age = 10.8 ± 3.5 years). ASD alone had significantly higher ABC scores. Subgroups of PWS and DS with a comorbid ASD positive screen or diagnosis had similarities in scores with the ASD only group, with subscale patterns unique to each syndrome. The ABC indicated worse maladaptive behaviors in children with ASD, including those with genetic syndromes. Although more studies are needed to evaluate the utility and the accuracy of the ABC as a tool to screen for ASD in special populations, it may be a useful adjunct in screening those children with PWS or DS who need more in depth ASD evaluation. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a complex multisystem disorder because of errors in genomic imprinting with severe hypotonia, decreased muscle mass, poor suckling, feeding problems and failure to thrive during infancy, growth and other hormone deficiency, childhood‐onset hyperphagia, and subsequent obesity. Decreased energy expenditure in PWS is thought to contribute to reduced muscle mass and physical activity but may also relate to cellular metabolism and disturbances in mitochondrial function. We established fibroblast cell lines from six children and adults with PWS and six healthy controls for mitochondrial assays. We used Agilent Seahorse XF extracellular flux technology to determine real‐time measurements of several metabolic parameters including cellular substrate utilization, Adenosine Triphosphate (ATP)‐linked respiration, and mitochondrial capacity in living cells. Decreased mitochondrial function was observed in the PWS patients compared to the healthy controls with significant differences in basal respiration, maximal respiratory capacity, and ATP‐linked respiration. These results suggest disturbed mitochondrial bioenergetics in PWS although the low number of studied subjects will require a larger subject population before a general consensus can be reached to identify if mitochondrial dysfunction is a contributing factor in PWS. [ABSTRACT FROM AUTHOR]

Dietary management is important to prevent severe obesity in individuals with Prader‐Willi syndrome (PWS); however, few studies have examined dietary intake and quality in youth with PWS. Our objective was to estimate intake of essential nutrients and diet quality in youth with PWS compared to those without PWS. Three‐day food records were used to estimate intake of energy, nutrients, nutrient‐density, foods, and adherence to healthy eating guidelines. Data were presented as medians and interquartile ranges with Mann–Whitney U and Fisher's test used to compare between groups with p <.05 considered significant. Youth with (n = 23) and without (n = 23) PWS were similar in age and sex distribution. The PWS group had a lower energy intake (p ≤.001), higher nutrient density (p =.003), and better adherence to guidelines (p =.007) compared to the control group. The proportion with nutrient intake from food below Estimated Average Requirement or Adequate Intake were similar between groups. Fiber, vitamin D, calcium, and potassium intake were below recommendations in 50% or more in both groups. The inclusion of supplement intake lowered the proportion below recommendations, except for fiber and potassium. Youth with PWS had a similar nutrient intake as those without PWS despite a lower energy intake, which could be attributed to higher diet quality. However, more than half of youth with PWS were at risk of inadequate fiber, vitamin D, calcium, and potassium intake. A greater emphasis on nutrient‐dense foods would improve nutrient intake, but supplements may be warranted in youth with PWS who do not meet recommendations. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a comprehensive understanding of temper outbursts in Prader–Willi syndrome (PWS). A survey was developed from interviews conducted with individuals with PWS and their caregivers. The survey was completed by 101 primary caregivers. The findings suggest that outburst frequency decreases with age while duration increases. Adolescents exhibited more severe behaviors than children or adults. No differences were found across gender or genetic subtype. Provocations fit into three themes: goal blockage, social injustice, and difficulty dealing with change. Distracting the person or giving them space to calm down were the only management strategies judged effective. Risperidone, sertraline, and fluoxetine were the most common medications prescribed for outbursts, though parents reported only minor effects. [ABSTRACT FROM AUTHOR]

Schaaf–Yang syndrome (SYS) was recently identified as a genetic condition resembling Prader–Willi syndrome. It is caused by mutations on the paternal allele of the MAGEL2 gene, a gene that has been mapped in the Prader–Willi critical region. Here, we present an infant with SYS who sadly died because of the combination of hypotonia, sleep apnea, and obesity. A heterozygous premature stop mutation in MAGEL2 was identified in the patient. The main factors reported in the mortality of SYS are lethal arthrogryposis multiplex congenita, fetal akinesia, and pulmonary problems. Our clinical report indicates that obesity and its complications are an important additional factor in the mortality associated with SYS. Therefore, we advise to strictly monitor weight and intensively treat overweight and obesity in SYS. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a genetic disorder with obesity, developmental delay, short stature, and behavioral abnormalities. The study aimed to assess the functional independence in children with PWS. The Functional Independence Measure for Children (WeeFIM) was used to evaluate 81 children with PWS (44 boys and 37 girls) with a median age of 11 years 1 month (range 2 years 8 months to 20 years 2 months) were recruited between January 2013 and December 2016. The mean total WeeFIM score was 103.8 (maximum 126). Sixty‐five patients (80%) had deletion type PWS, 16 (20.0%) had nondeletion type. The scores were 103.6 ± 18.5 for deletion and 104.8 ± 18.3 for nondeletion type (p = .405), 104.8 ± 19.3 in boys and 102.6 ± 17.3 in girls (p = .293). The mean self‐care, mobility, and cognition scores were 47 (maximum 56), 33 (maximum 35), and 24 (maximum 35), respectively. All total scores and 18 subscores in the three functional domains were positively correlated with age (p < .05). Most children required assistance in problem‐solving, comprehension, and expression. The WeeFIM identified the strengths and limitations of children with PWS and confirmed that support and supervision were needed in cognitive and self‐care tasks. [ABSTRACT FROM AUTHOR]

Deaths among children with Prader–Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus‐pituitary‐adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5–3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age‐matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3–27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2–23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3–48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5–22.0 pg/ml), 15.6 (IQR, 11.9–21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7–30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis. [ABSTRACT FROM AUTHOR]

MAGEL2 is the paternally expressed gene within Prader–Willi syndrome critical region at 15q11.2. We encountered three individuals in whom truncating mutations of MAGEL2 were identified. Patients 1 and 2, siblings born to healthy, non‐consanguineous Japanese parents, showed generalized hypotonia, lethargy, severe respiratory difficulty, poor feeding, and multiple anomalies including arthrogryposis soon after birth. We carried out whole‐exome sequencing, which detected a MAGEL2 mutation (c.1912C>T, p.Gln638*, heterozygous). The patients’ father was heterozygous for the mutation. Patient 3 was a female infant, showed respiratory difficulty reflecting pulmonary hypoplasia, generalized hypotonia, feeding difficulty and multiple anomalies soon after birth. Targeted next‐generation sequencing detected a novel heterozygous mutation in MAGEL2 (c.3131C>A, p.Ser1044*). This mutation was not found in the parents. MAGEL2 mutations, first reported to be the cause of the Prader–Willi like syndrome with autism by Schaaf et al. (2013) Nature Genetics, 45: 1405–1408 show the wide range of phenotypic spectrum from lethal arthrogryposis multiplex congenital to autism spectrum disorder (ASD) and mild intellectual disability (ID). Our results indicate that MAGEL2 mutations cause multiple congenital anomalies and intellectual disability accompanied by arthrogryposis multiplex congenita and various endocrinologic abnormalities, supporting that the view that clinical phenotypes of MAGEL2 mutations are variable. [ABSTRACT FROM AUTHOR]

The two imprinting syndromes Temple syndrome (TS14) and Prader-Willi syndrome (PWS) share many features in infancy and childhood. TS14 is an important, yet often neglected, differential diagnosis to PWS. We wanted to assess the frequency of TS14 among patients tested for PWS. In all samples submitted to our lab for genetic PWS testing during 2014 and 2015, we consecutively conducted additional analyses for TS14. A total of 143 samples were included. The most frequent indications for testing were developmental delay, overweight, and hypotonia. For TS14 testing, we performed a methylation-sensitive MLPA-kit detecting deletions and methylation aberrations in chromosomal region 14q32. TS14 was confirmed in 3 out of 143 patients (2.1%). In comparison, PWS was also confirmed in three patients. Brief clinical descriptions of the TS14 patients are presented. Temple syndrome is presumably underdiagnosed, and should be considered when testing children for PWS. [ABSTRACT FROM AUTHOR]

High prevalence of behavioral and psychiatric disorders in adults with Prader-Willi Syndrome (PWS) has been reported in last few years. However, data are confusing and often contradictory. In this article, we propose a model to achieve a better understanding of the psychopathological features in adults with PWS. The study is based on clinical observations of 150 adult inpatients, males and females. Non-parametric statistics were performed to analyse the association of psychopathological profiles with genotype, gender and age. We propose a model of psychiatric disorders in adults with PWS based on cognitive, emotional and behavioural issues. This model defines four psychopathological profiles: Basic, Impulsive, Compulsive, and Psychotic. The Basic profile is defined by traits and symptoms that are present in varying degrees in all persons with PWS. In our cohort, this Basic profile corresponds to 55% of the patients. The rest show, in addition to these characteristics, salient features of impulsivity (Impulsive profile, 19%), compulsivity (Compulsive profile, 7%), or psychosis (Psychotic profile, 19%). The analysis of factors associated with different profiles reveals an effect of genotype on Basic and Psychotic profiles (Deletion: 70% Basic, 9% Psychotic; Non-deletion: 23% Basic, 43% Psychotic) and a positive correlation between male sex and impulsivity, unmediated by sex hormone treatment. This is a clinical study, based on observation proposing an original model to understand the psychiatric and behavioural disorders in adults with PWS. Further studies are needed in order to test the validity of this model. [ABSTRACT FROM AUTHOR]

Prader-Willi Syndrome (PWS) is caused by a genetic imprinting abnormality resulting from the lack of expression of the paternal genes at 15q11-q13. Intellectual disability, low muscle tone, and life-threatening hyperphagia are hallmarks of the phenotype. The need for the Heimlich maneuver, death from choking, and pulmonary infection occur in a disproportionally high number of persons with PWS. The widely held belief is that eating behaviors are responsible for choking and aspiration; yet, no investigation had sought to determine if swallowing impairments were present in persons with PWS. To address this research and clinical gap, simultaneous videofluoroscopy and nasal respiratory signals were used to record swallowing function and breathing/swallowing coordination in 30 participants with PWS. Subjects consumed thin liquid and barium cookies under two randomized conditions as follows: (i) controlled (cues to swallow and standardized bolus sizes); (ii) spontaneous (no cues or bolus size control). Under videofluoroscopy, the cohort showed disordered pharyngeal and esophageal swallowing in both conditions with disturbances in timing, clearance, and coordination of swallowing with the respiratory cycle. No participant showed a sensory response such as attempting to clear residue or coughing; thereby supporting the lack of overt symptoms. We conclude that the high death rate from choking and pulmonary infection in children and adults with PWS may be related, in part, to underlying, asymptomatic dysphagia. The combination of rapid eating and dysphagia would increase the risk of aspiration-related morbidity and mortality. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder associated with maladaptive social behavior, hyperphagia and morbid obesity. Orexin A is a hypothalamic neuropeptide important as a homeostatic regulator of feeding behavior and in energy metabolism through actions in the lateral hypothalamus. Dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia seen in PWS and we sought to assess orexin A levels in PWS relative to controls children. Morning fasting plasma orexin A levels were analyzed in 23 children (aged 5-11 years) with genetically confirmed PWS and 18 age and gender matched healthy unrelated siblings without PWS. Multiplex immune assays utilized the Milliplex Human Neuropeptide Magnetic panel and the Luminex platform. Natural log-transformed orexin A data were analyzed using general linear model adjusting for diagnosis, gender, age, total body fat, and body mass index (BMI). Plasma orexin A levels were significantly higher ( P < 0.006) in children with PWS (average ±SD = 1,028 pg/ml ± 358) compared with unrelated siblings (average ±SD = 609 pg/ml ± 351; P < 0.001). Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. Further studies are warranted to better understand the complex relationship between orexin A levels and the problematic behaviors consistently found in individuals with PWS. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome is a congenital neurodevelopmental disorder resulting from deletion of the paternal copies of genes within the chromosome region 15q11-q13. Patients with Prader-Willi syndrome often exhibit excessive daytime sleepiness, excessive appetite, and obesity. As is the case in narcolepsy, orexin (hypocretin) may be responsible for these symptoms. However, reports showing cerebrospinal fluid orexin levels in Prader-Willi syndrome patients have been limited. The aim of this study was to examine the relationship between the characteristic symptoms of Prader-Willi syndrome and cerebrospinal fluid orexin levels. We clinically identified 14 Prader-Willi syndrome patients and examined their cerebrospinal fluid orexin levels. A total of 12 patients with a 15q11-q13 deletion and two patients with maternal uniparental disomy of chromosome 15 were identified. A total of 37 narcoleptic patients and 14 idiopathic hypersomnia patients were recruited for comparison. Cerebrospinal fluid orexin levels (median [25-75 percentiles]) in the 14 Prader-Willi syndrome patients were intermediate (192 [161-234.5] pg/ml), higher than in the narcoleptic patients, but lower than in the idiopathic hypersomnia patients. Body mass index of the Prader-Willi syndrome patients was higher than in the narcoleptic and idiopathic hypersomnia patients. There was also a negative correlation between Epworth sleepiness scale scores and orexin levels in Prader-Willi syndrome patients. Decreased cerebrospinal fluid orexin levels in Prader-Willi syndrome may play an important role in severity of obesity and excessive daytime sleepiness. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is a rare genetic disorder that results from lack of expression of paternally-derived genes on chromosome 15q11-13; caused by a deletion (DEL), uniparental disomy (UPD), or a rare imprinting center defect. PWS is associated with a distinct behavioral phenotype that in some respects overlaps with autism spectrumdisorder (ASD), a neurodevelopmental disorder characterized by restricted or repetitive behaviors (RRBs) and social-communication impairment. The goal of this review was to (i) review published literature investigating core ASD symptoms in PWS and (ii) provide a prevalence estimate of ASD in PWS. Two independent reviewers searched Medline, CINAHL, PsychINFO, Embase, and Web of Science to find studies that answered the research questions. Individuals with PWS demonstrate significant levels of RRBs and socialcommunication impairment, in some reports reaching similar levels to those of non-PWS ASD comparison groups. Individuals with UPD had more social-communication impairment than those with DEL. Of 786 PWS participants, 210 (26.7%) were reported as meeting criteria for ASD, either based on clinical diagnosis or by exceeding clinical cut-points on relevant ASD symptom measures. In studies that distinguished genetic subtypes, rates of ASD were higher in individuals with PWS with UPD (67 of 190; 35.3%) than those with DEL (47 of 254; 18.5%). Published data on the association of PWS and ASD to date are limited to sample means of 8 years of age and older. Further research is needed to identify early markers of ASD in PWS children, to support earlier diagnosis and intervention for this important comorbidity. [ABSTRACT FROM AUTHOR]

This report describes the phenotype, from early childhood to adolescence, of a girl with Angelman syndrome (AS) born following a maternal transmission of a germline paternal 15q11.2-q13 deletion. During early childhood, she showed a typical AS phenotype, such as jerky movements, poor sleep, high voltage electroencephalography pattern, epilepsy, and a severe developmental disability. As she grew older, indications of phenotypical traits similar to Prader-Willi syndrome (PWS) appeared, in particular hyperphagic behavior and a body fat distribution similar to that reported in PWS. She generally showed cheerful AS behavior and had the characteristic outbursts of laughter, but her attitude to other people did not reflect the usual shared enjoyment of interaction seen in children with AS. In unfamiliar surroundings, she withdrew socially, similar to children with PWS, and her insistence on the same, rigid routines was similar to behavior patterns in PWS. The dysmorphic facial features that characterize AS were blurred in adolescence. The specified features that this AS patient had in common with PWS were hardly incidental and, if verified by upcoming case reports of children born to women with a paternal 15q11.2-q13 deletion, they may show new aspects of genetic imprinting. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is an obesity-related genetic condition, most commonly due to a paternal deletion of the chromosome 15q11-q13 region. PWS is characterized by growth hormone deficiency, infantile hypotonia and feeding problems, hypogenitalism/hypogonadism, increased pain threshold and thermal instability, decreased gastric motility, and hyperphagia in childhood leading to severe obesity. Neuro-endocrine peptides are known to influence gastric function and pain sensation which led us to measure a specific peptide that may be involved [i.e., neurotensin (NT)] in PWS and compared with unrelated control siblings. Overnight fasting plasma NT levels were obtained from 23 children with confirmed PWS (age: 8.2 ± 2.0 years; range: 5-11 years) and 18 unaffected, unrelated siblings (age: 8.2 ± 2.3 years; range: 5-11 years) and measured using Multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Plasma NT levels were natural log-transformed and analyzed by ANOVA with adjustments for age, gender, and body mass index (BMI). No difference was found in plasma NT levels for gender, age or BMI or significant correlations seen with age or BMI. Higher plasma NT levels ( P < 0.001) were seen in PWS children (mean of 626 ± 238 pg/ml) compared with unaffected, unrelated siblings (mean of 371 ± 236 pg/ml). Plasma levels were also higher in children with maternal disomy 15 (736 ± 182 pg/ml) compared with those having the deletion subtype (548 ± 247 pg/ml, P < 0.04). Although no measures for pain threshold, thermal instability or gastric motility were performed in our study participants, higher plasma NT levels were found in PWS children. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Hyperphagia, developmental delays, and maladaptive behaviors are common in Prader-Willi syndrome (PWS) likely resulting in heightened parental stress. Objectives were to evaluate stress, describe usefulness of coping behaviors, and assess the impact of a structured Plan of Care (PC) on parents with children with PWS. Parents answered Perceived Stress Scale (PSS-14), Coping Health Inventory for Parents (CHIP), and narrative/demographic surveys. The PC was introduced to a cohort of parents after completion of the PSS-14 and CHIP and re-administered 4-6 month after the introduction of the PC. Higher parental stress (n = 57) was observed compared to the general population, and associated with parent's age, number of children living at home, and child's age and residential setting. 'Maintaining family integration, cooperation, and an optimistic definition of the situation' was the most useful coping pattern. Thirty-eight parents answered the PSS-14 and CHIP after the PC. Parental stress decreased after the PC ( P = 0.035). Coping behaviors related to 'maintaining family integration' increased after the PC ( P = 0.042). Women and men preferred different coping patterns before and after the PC. In conclusion, parental stress is increased in PWS, and a PC decreased stress and increased coping behaviors related to family stability for parents with children with PWS. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Psychiatric disorders such as psychosis are highly prevalent in adults with Prader-Willi syndrome (PWS). However, knowledge about the presence and progression of psychiatric disorders in children with PWS is very limited. Sixty-one children with PWS aged 7-17 years were tested using the Diagnostic Interview Schedule for Children (DISC) and Compulsive Behaviour Checklist (CBC), and 38/61 were retested after 2 years. Prevalence of psychiatric disorders and the association with age, gender, genetic subtype, and total IQ were assessed. In addition, occurrence and characteristics of compulsions were determined. Prior to the study, two boys were known with psychotic symptoms and treated with antipsychotics. At baseline, none scored positive for psychotic disorder. During the follow-up, only one boy with known psychotic symptoms required a dose adjustment of his antipsychotic medication. After 2 years, none of the children had a psychotic disorder according to the DISC. Oppositional defiant disorder (ODD) was the most common diagnosis and present in 20% of children with PWS, and this was not associated with age (β = −0.081, P = 0.546), gender (β = 0.013, P = 0.923), genetic subtype (β = −0.073, P = 0.584), or total IQ (β = −0.150, P = 0.267). The most common compulsions were hoarding and fixed hygiene sequences. In our large group of 61 children with PWS, the majority had no psychotic disorder and no progression was found during 2-year follow-up. ODD was present in 20% of children. No changes in the prevalence of psychiatric disorders were found during the 2-year follow-up study and genetic subtype was not related to psychosis, depression, or ODD. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes from the 15q11-q13 region and reportedly rearranged as a cause of autism. Additionally, increased inflammatory markers and features of autism are reported in PWS. Cytokines encoded by genes involved with inflammation, cell proliferation, migration, and adhesion play a role in neurodevelopment and could be disturbed in PWS as abnormal plasma cytokine levels are reported in autism. We analyzed 41 plasma cytokines in a cohort of well-characterized children with PWS between 5 and 11 years of age and unaffected unrelated siblings using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Data were analyzed using ANOVA testing for effects of diagnosis, gender, body mass index (BMI) and age on the 24 cytokines meeting laboratory criteria for inclusion. No significant effects were observed for age, gender or BMI. The log-transformed levels of the 24 analyzable cytokines were examined simultaneously using MANOVA adjusting for age and gender and a main effect of diagnosis was found ( P-value <0.03). Four of 24 plasma cytokine levels (MCP1, MDC, Eotaxin, RANTES) were significantly higher in children with PWS compared with controls and classified as bioinflammatory chemokines supporting a disturbed immune response unrelated to obesity status. BMI was not statistically different in the two subject groups (PWS or unaffected unrelated siblings) and chemokine levels were not correlated with percentage of total body fat. Additional studies are required to identify whether possible early immunological disturbances and chemokine inflammatory processes found in PWS may contribute to neurodevelopment and behavioral features. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Food-related behavior problems are well documented in Prader-Willi syndrome (PWS), with impaired satiety, preoccupation with food and negative food-related behaviors (such as taking and storing food) frequently reported as part of the behavioral phenotype of older children and adults. Food-related behavior problems in other genetic neurodevelopmental syndromes remain less well studied, including those seen in Angelman Syndrome (AS), the 'sister imprinted disorder' of PWS. Food-related behavior problems were assessed in 152 participants each with one of five genetic neurodevelopmental syndromes - PWS, AS, 1p36 deletion, Cornelia de Lange, and fragile X. Predictably, levels of food-related behavior problems reported in participants with PWS significantly exceeded those of at least one other groups in most areas (impaired satiety; preoccupation with food; taking and storing food; composite negative behavior). However, in some areas people with AS were reported to display food-related problems at least as severe as those with PWS, with the AS group reported to display significantly more food-related behavior problems than at least one comparison group on measures of taking and storing food, composite negative behaviors, impaired satiety and preoccupation with food. Over 50% of participants in the AS group scored above the median point of the distribution of PWS scores on a measure of taking and storing food. These findings indicate further investigation of eating problems in AS are warranted and have implications for current theoretical interpretations of the behavioral differences between AS and PWS. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]