Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org ) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC \"Behavior Outcomes Working Group\" sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive-compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.

Prader-Willi syndrome (PWS) is the first multi-systemic genetic disorder known to be caused by imprinting defect. The clinical manifestations of PWS vary with age. At the prenatal stage, decreased fetal movements are frequent. The major clinical manifestations during neonatal period include hypotonia, weak cry, poor suck and feeding difficulties. Growth retardation and delayed language and motor development are observed during infancy. Short stature, small hands and feet, cognitive deficiency are noticed in the childhood. At adolescence, prominent growth retardation, obesity, gonadal dysplasia, abnormal behavior and learning difficulties are the major issues. Morbid obesity caused by insatiable appetite is the major factor for prognosis. Early diagnosis and intervention play a significance role in improving the quality of life, preventing serious complications and prolonging survival. This guideline covers the clinical manifestations, developmental process, pathogenesis, molecular diagnosis and genetic counseling of PWS, with an aim to provide reference for clinicians for early identification, proper intervention and genetic counseling for this disease.

This article is an update of the best practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes published in 2010 in BMC Medical Genetics [1]. The update takes into account developments in terms of techniques, differential diagnoses and (especially) reporting standards. It highlights the advantages and disadvantages of each method and moreover, is meant to facilitate the interpretation of the obtained results - leading to improved standardised reports.

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BACKGROUND: Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events.
OBJECTIVE: The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS.
METHODS: We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries.
METHODS: Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN).
CONCLUSIONS: Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks.

Growth hormone (GH) is approved by the US Food and Drug Administration (FDA) for use in pediatric patients with disorders of growth failure or short stature and in adults with growth hormone deficiency (GHD) and HIV/AIDS wasting and cachexia. For pediatric patients, guidelines for the use of GH have been developed by several organizations that have identified specific criteria for initiating GH therapy for each FDA-approved indication. Guidelines for adults have also been developed and include recommendations for transition (adolescent) patients with GHD. These patients are often treated with GH as children but may require continued treatment as young adults to attain full skeletal mineralization and improve cardiovascular risk factors. Adult and pediatric guidelines are supported by efficacy and safety studies, which show that, when started at an early age, GH treatment can increase growth velocity and that GH is safe and well-tolerated. We summarize the guidelines that are available for all FDA-approved indications among pediatric and transition patients. Adherence to these guidelines will help to ensure that patients with disorders of growth failure or short stature receive the necessary therapy to increase linear growth and transition smoothly to healthy adulthood.

BACKGROUND: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct neurodevelopmental genetic disorders that map to 15q11-q13. The primary phenotypes are attributable to loss of expression of imprinted genes within this region which can arise by means of a number of mechanisms. The most sensitive single approach to diagnosing both PWS and AS is to study methylation patterns within 15q11-q13; however many techniques exist for this purpose. Given the diversity of techniques available, there is a need for consensus testing and reporting guidelines.
METHODS: Testing and reporting guidelines have been drawn up and agreed in accordance with the procedures of the UK Clinical Molecular Genetics Society and the European Molecular Genetics Quality Network.
RESULTS: A practical set of molecular genetic testing and reporting guidelines has been developed for these two disorders. In addition, advice is given on appropriate reporting policies, including advice on test sensitivity and recurrence risks. In considering test sensitivity, the possibility of differential diagnoses is discussed.
CONCLUSIONS: An agreed set of practice guidelines has been developed for the diagnostic molecular genetic testing of PWS and AS.

The Paediatric and Adolescent Endocrine and Diabetes Society of South Africa (PAEDS-SA) recommends, in line with other international groups, that growth hormone (GH) therapy be considered for children and adolescents with significantly short stature and poor growth velocity in the following instances: GH deficiency; Turner syndrome; Prader-Willi syndrome; small-for-gestational-age children with failure of catch-up growth; idiopathic short stature; and chronic renal insufficiency. We have produced treatment guidelines for the use of GH, designed to allow flexibility to determine coverage on a case-by-case basis. We further recommend that when used for growth promotion, GH therapy should be initiated and monitored by, or in consultation with, a paediatric endocrinologist.

BACKGROUND: Prader-Willi Syndrome (PWS) is a complex human genetic disease arising from a loss of paternal allele expression of imprinting genes on chromosome 15q11-q13. Normally the CpG islands at this site are heavily methylated in the maternal allele, but unmethylated in the paternal allele and therefore activated in gene expression. only the methylated allele should present in pws patients when methylation-specific pcr (msp) is analyzed.
METHODS: This paper reports an analysis of PWS in Thai patients using consensus diagnostic criteria based on a combination of clinical data, basic G-banding and fluorescence in situ hybridization (FISH) cytogenetics, PCR-based methylation assay, and bisulfite sequencing of the CpG islands of SNRPN to confirm 15q deletion or the methylation pattern of the SNRPN promoter and exon 1. Lack of complete clinical reports or inadequacy of the minimum laboratory support required had made it difficult to diagnose PWS, Angelman syndrome and other microdeletion disorders.
RESULTS: Accuracy of 100% was obtained for diagnosis of the PWS study patients using the minimum requirements necessary. A total of 20 patients were diagnosed as PWS based on clinical criteria and the scoring tool for PWS, and the same approach was applied to four separate patients with some unmatched criteria but phenotypic similarity to PWS. Findings showed that 70% of those clinically diagnosed as PWS patients (14/20) had a deletion at 15q11-q13 according to FISH, while all 20 patients showed MSP positive of SNRPN gene. Six cases (30%) without a paternal deletion were confirmed to have maternal uniparental disomy (mUPD) of PWS by MSP and methylation sequencing approaches. Noteworthy, two of the six cases with mUPD were 3.5 year-old twins. None of the five cases with scores lower than the reported consensus criteria showed positive G-band, FISH or MSP results.
CONCLUSIONS: We demonstrate here the high power of combining clinical findings, FISH and MSP in definitive diagnosis of PWS and in distinguishing between the two major different types of molecular mechanisms. No false positives or false negatives were observed in our analysis.