My NCBI Sign In
Jump to: Authorized Access | Attribution | Authorized Requests

Study Description

This observational study will involve the comprehensive assessment of the medical, behavioral and nutritional history and the clinical features of individuals with Prader-Willi syndrome and individuals with features of PWS-like/EMO. A blood sample will be obtained from the participants in order to create a DNA and RNA repository. In those PWS participants with a known deletion a blood sample will be collected for DNA in order to perform array comparative genome hybridization (aCGH) microarray or Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA) studies to characterize the extent of the deletion. DNA samples will be sent to the Consortium Center at Baylor College of Medicine for the performance of the aCGH studies and to either Dr. Driscoll or Dr. Butler lab for MS-MLPA analysis. No drugs or treatments will be administered through this protocol.

Our goal is to enroll as many participants as possible over a 8 year period. Currently we have enrolled 297 total subjects of which 265 have PWS and 32 EMO. Our original goal was to have enrolled over the first 5 years a clinical database of 200 individuals with PWS and 100 with EMO. We have exceeded expectations in PWS enrollment, but have fallen short in the enrollment of individuals with EMO. Therefore, we would like to reset our goals. We now propose to have an enrollment goal of 400 total subjects of which 350 will have PWS and 50 will have EMO. Eligible participants will be initially enrolled in the natural history study from the 4 clinic sites currently involved with PWS (University of Florida, Kansas University Medical Center, Vanderbilt University and University of California at Irvine). Participants assessed will serve to provide a background of information and a willing cohort for future interventional studies.

All participants will have had standard genetic testing at a commercial laboratory prior to entry into the study. The PWS participants will be classified into one of the 3 main molecular classes (deletion, UPD and ID). The EMO participants will have had laboratory testing ruling out PWS and chromosomal aneuploidy (e.g., trisomy 21, Klinefelter syndrome, etc.). Going forward we feel it is important that all newly recruited EMO subjects have an aCGH as part of their evaluation so we can identify those with discrete deletions, duplications or copy number variants (CNV) and compare them to those without aCGH abnormalities. The participants will be assessed annually (0-3 years of age) or biennially (> 3 years) in the Clinical Research Center (or equivalent facility) using standardized protocol including photographs for documentation purposes to compare the evolution of the clinical phenotype.

  • Study Type: Case Set
  • Number of study subjects that have individual level data available through Authorized Access: 200

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

The PWS group will have had appropriate molecular and cytogenetic testing to confirm a diagnosis of PWS (i.e., chromosomes, FISH 15, DNA methylation, and where necessary, DNA polymorphism studies), and categorized into the appropriate molecular group (i.e., deletion, uniparental disomy and imprinting defect). It should be noted that appropriate genetic testing can correctly identify >99% of all cases of PWS (Glenn et al. 1997). Imprinting defect patients will be recruited, but the low frequency in this group will make statistical comparisons with the other two molecular classes challenging. Participants will be excluded from this part of the study if they have not had genetically proven PWS.

The EMO group will be selected solely based on a documented medical chart history of their weight having exceeded 150% of Ideal Body Weight (IBW) or a Body Mass Index (BMI) of greater than the 97% before 4 years of age. Participants will be excluded from this part of the study if they have a chromosomal aneuploidy or Fragile X as the cause of their obesity. All EMO patients will have had a chromosomal or aCGH analysis, DNA methylation testing for PWS, MC4R mutation analysis and a serum leptin prior to entry to the study

Study History

Prader-Willi syndrome (PWS) is a complex neurobehavioral syndrome whose main clinical features include obesity, hyperphagia, hypotonia, cognitive impairment, a distinct behavioral phenotype, hypogonadism, and neonatal failure-to-thrive (Cassidy, 1997). The genetic defect has been localized to a 2 megabase region of chromosome 15q11-q13. It is a contiguous gene syndrome with the loss of expression of several genes resulting in the complete phenotype. It is postulated that a loss of expression of one gene in this region may lead to some, but not all the features of PWS. As PWS is the most common recognized genetic cause of morbid obesity, a growing number of morbidly obese children are being referred from the general pediatric clinics to the pediatric genetics and pediatric endocrinology for evaluation of PWS. Many of these children clinically and molecularly do not have PWS, but share several similarities to PWS. However, they also have some distinct differences from PWS. We refer to these individuals as the Early-onset Morbid Obesity (EMO) population

Early-onset Morbid Obesity

Childhood obesity has become a health problem of epidemic proportions. The prevalence of obesity has been increasing significantly over the last three decades in every age group. However, the age group with the smallest increase are those children less than 4 years of age (Ogden et al, 1997). This finding suggests that metabolic or genetic factors play a greater role than the environment in the development of obesity in young children. Many children who become obese before the age of 4 years are therefore referred to either genetics or endocrinology to evaluate for possible identifiable etiologies of their obesity.

The diagnosis of PWS is often entertained in children who develop obesity early in life. We refer to individuals who develop obesity before the age of 4 years as the Early-onset Morbid Obesity (EMO) population. Many of the EMO children have similarities to PWS, including developmental delay, learning problems, and behavioral problems. However, several of the EMO children also have distinct differences from PWS, including tall stature, a large head circumference, lack of hypotonia, and lack of neonatal FTT.

Very little is known about the etiology of EMO. A few genes have been described which can cause EMO, but the vast majority of patients are undiagnosed at this point. One hypothesis is that a mutation in one of the genes in the PWS region 15q11-q13 may result in the EMO phenotype. However, other monogenetic mutations may also be responsible for the early onset obesity in the EMO population.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Related Resources
Authorized Data Access Requests
Study Attribution