Intellectual and developmental disabilities (IDDs), including Prader-Willi syndrome, are a primary focus of NICHD’s research. Prader-Willi syndrome encompasses a set of related conditions with a range of symptoms that affect eating and metabolism, growth, behavior, and intellectual development.
NICHD, part of the NIH within the U.S. Department of Health and Human Services, is one of many federal entities supporting research on Prader-Willi syndrome. NICHD’s portfolio covers a variety of topics related to Prader-Willi syndrome, including its etiology, epidemiology, and treatment. The institute also supports professional training and the development of research infrastructure that will facilitate research in Prader-Willi syndrome and other IDDs.
NICHD studies the cellular, molecular, and genetic mechanisms associated with Prader-Willi syndrome and other types of intellectual and developmental disabilities (IDDs).
Through its IDD Branch, the institute supports research and research training aimed at understanding IDDs, including Prader-Willi syndrome, and on ways to detect and treat these disorders and their symptoms. In recent years, the IDD Branch portfolio has expanded its support of projects related to the roles of methylation, histone modification, genomic imprinting, and other factors related to epigenetic disorders such as Prader-Willi syndrome. This expansion reflects increased attention within the research field for these topics.
In addition to individual projects on Prader-Willi syndrome and epigenetic disorders, the Branch supports the Angelman, Rett & Prader-Willi Syndromes Consortium (ARPWSC), part of the larger NIH Rare Diseases Clinical Research Network (RDCRN). The RDCRN includes 19 distinct Rare Disease Clinical Research Consortia that work together to improve the availability of information, treatment, clinical studies, and general awareness of rare diseases for patients, families, and the medical/research community. NICHD supports three consortia: ARPWSC, the Urea Cycle Disorders Consortium, and the Sterol & Isoprenoid Research (STAIR) Consortium.
Intellectual and Developmental Disabilities Branch-supported research has led to the following advances in PWS research:
- Researchers have created new mouse models for Angelman syndrome that also affect the imprinting center shared with PWS.
- Research shows that many epigenetic disorders share features, including altered MECP2 expression in Prader-Willi, Rett, and Angelman syndromes (Nagarajan et al., 2006). Mutations on the MECP2 gene cause most cases of Rett syndrome, a disorder characterized by a loss of language and of cognitive and fine motor skills that occurs mostly in girls.
- By placing a deletion of the chromosome 15 imprinting center on a different genetic strain, researchers were able to create a mouse model for studying PWS (Chamberlain et al., 2004).
- To address the problem of excessive eating that occurs in PWS, researchers developed a questionnaire to study hyperphagia (Dykens et al., 2007), defined as excessive hunger and abnormally large intake of solid foods. The same group of investigators also detected neural differences in visual responses to food stimuli among people with different forms of PWS based on the food's composition and suitability for consumption.
The Unit on Metabolism and Neuroendocrinology, which is within the Program on Developmental Endocrinology and Genetics in NICHD's Division of Intramural Research (DIR), also conducts studies related to some of the features of PWS, specifically those characteristics associated with food behaviors and metabolism. Recent findings include low levels of brain-derived neurotrophic factor, a chemical that plays a role in the leptin signaling pathway that regulates appetite and energy balance. For more information on this research and other findings from the unit, visit https://annualreport.nichd.nih.gov/2012/umn.html.
In addition, the Section on Growth and Obesity, also within the DIR, conducts research to understand the metabolic and behavioral factors involved in determining regulation of body weight and body composition during childhood. This work includes studies of brain-derived neurotrophic factor and leptin as well as of hyperphagia and other conditions and health problems related to obesity. Visit https://annualreport.nichd.nih.gov/2012/sgo.html for more on this research.
- In 2009, NICHD helped to sponsor the First International Conference on Hyperphagia as a way to learn more about hunger and excessive hunger, the drive to overeat, and obesity associated with certain intellectual and development disabilities (IDDs), including Prader-Willi syndrome. Objectives included discussion of both similar and unique aspects of hyperphagia across IDDs, facilitation of more accurate and earlier diagnosis of hyperphagia, and understanding of the management and quality-of-life issues faced by families affected by hyperphagic disorders. Watch conference presentations from the Second International Conference on Hyperphagia in 2012.
- Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers (EKSIDDRCs) support basic, clinical, and translational researchers whose goals are to advance understanding of a variety of conditions and topics related to IDDs, including Prader-Willi syndrome. The Centers' research services include information technology, bioinformatics, and biostatistics as well as gene array, proteomics, and behavioral and clinical core services.
- Global PWS Registry The Foundation for PW Research maintains this registry to learn about PWS from individuals and families living with the condition.