Down syndrome is a chromosomal disorder caused by an error in cell division that results in the presence of an additional copy of chromosome 21 (trisomy 21) or additional chromosomal 21 material. Named after John Langdon Down, the first physician to describe the syndrome systematically, Down syndrome is the most frequent chromosomal cause of mild to moderate intellectual disability. It occurs in all ethnic and economic groups. People with the syndrome also are at a greater risk for many other conditions, such as congenital heart disease, hearing loss, leukemia, and dementia and memory loss similar to Alzheimer disease.
The NICHD has conducted and supported Down syndrome research since its founding, including development of animal models to help study the syndrome, examination of specific genes and gene groups that may play a role in the syndrome, understanding how maternal age plays a role in the disorder, and development of new methods of diagnosis prenatally and postnatally. Additional research activities are described below.
The Institute's portfolio covers a broad range of research areas, including the causes, treatment, and prevention of Down syndrome.
Since 2011, the Institute has led the Down Syndrome Consortium, a public-private collaboration that provides a forum for promoting the Down Syndrome Directions: NIH Research Plan on Down Syndrome (2014) and fosters the exchange of information on biomedical and biobehavioral research on the syndrome. Consortium members, who represent public and private organizations, work to avoid duplication of research efforts and to inform the Down syndrome community of research advances. In addition to the NICHD, the Consortium includes the following organizations (in alphabetical order):
- American Academy of Pediatrics
- American Association on Intellectual and Developmental Disabilities
- Association of University Centers on Disabilities
- Down Syndrome Affiliates in Action
- Down Syndrome Medical Interest Group
- Down Syndrome Research and Treatment Foundation
- Global Down Syndrome Foundation
- International Mosaic Down Syndrome Association
- Jérôme Lejeune Foundation
- National Down Syndrome Congress
- National Down Syndrome Society
- Research Down Syndrome
- Special Olympics International
In 2013, the Consortium launched its Down syndrome registry, DS-Connect®, which facilitates contacts and information sharing among people with Down syndrome and their family members, researchers, and parent and support groups safely and confidentially. Creation of this registry was one of the principal recommendations of the Down Syndrome Research Plan.
The Institute has also played a lead role in the trans-NIH Working Group on Down Syndrome, which developed the Research Plan, and aims to coordinate research activities across the NIH.
Some of the Institute's work related to Down syndrome is supported through its Intellectual and Developmental Disabilities Branch (IDDB). A key focus for the IDDB is exploring treatments for Down syndrome, including agents that improve intellectual development and cognitive performance.
The Repository for Mouse Models for Cytogenetic Disorders , a distribution center supported by the NICHD, provides mice for research on Down syndrome and other disorders. Because of similarities between certain mouse and human chromosomes, mouse models have allowed significant advances in understanding potential treatments for Down syndrome. For example, researchers currently are studying the use of the drug memantine, which supports cognition in mice and is approved for treating Alzheimer's dementia in humans, to improve the cognitive abilities of young adults with Down syndrome.
Improvements in learning in a Down syndrome animal model
Using a mouse model for Down syndrome, NICHD researchers showed that by administering neuroprotective peptides (small protein sub units) to mice before birth, they perform better on memory and learning tasks as adults. The peptides, NAP and SAL, are sub units of two proteins that are important in brain development because they enhance the ability of brain cells to receive and transmit signals, and enable them to survive. The mice in the study had an extra copy of mouse chromosome 16, which has counterparts to 55% of the genes on human chromosome 21. Mice with the extra chromosomal material that were treated with NAP and SAL in the womb learned as well as mice that did not have the extra chromosome and significantly faster than mice with the extra chromosome that were treated with saline solution (placebo).
In an earlier study, NICHD researchers showed that when mice with the extra copy of chromosome 16 were treated with NAP and SAL in the womb, they achieved developmental milestones earlier than did untreated mice. In this earlier study, the researchers examined developmental milestones for sensory, motor skill, and muscle tone in the first three weeks of life. Together these study findings show that NAP and SAL treatments improve both physical development and learning ability in a mouse model for Down syndrome.
Other research focuses on the causes and pathophysiology of Down syndrome. The IDDB supports a broad range of activities in this area, including explorations of the signaling pathways, metabolic processes, and mitochondrial functions that affect the development of people with Down syndrome.
Some other recent scientific advances related to Down syndrome include:
- An assessment of gastrointestinal anomalies by sex, race, and ethnicity (PMID: 19021635)
- Identification of modifier genes located on other chromosomes that affect variability in Down syndrome features
- Evidence from animal models of genes involved in craniofacial and brain development (PMID: 19764029) (PMID: 20639873) (PMID: 17431903)
- Identification of specific genes that are candidates for the features of Down syndrome (PMID: 12466854)
- Assessment of the benefits of early intervention programs (PMID: 21532932)
Other organizational units also support or conduct research related to Down syndrome. For example:
- The NICHD Developmental Biology and Structural Variation Branch examines areas relevant to normal and abnormal development, such as the processes, patterns, and genetics of organ and central nervous system development. The Branch also supports research on epigenetic and genomic regulation of gene expression, and on developmental neurobiology.
- The Institute's Section on Gamete Development, which is part of the Division of Intramural Research (DIR), researches meiosis (a cellular process of reduction and division, pronounced mahy-OH-sis) to understand the mechanisms that lead to chromosome missegregation, which can cause Down syndrome and other disorders.
- In addition, the DIR's Section on Implantation and Oocyte Physiology validates model organisms for their use in studying chromosomal abnormalities in human embryos and identifying new tests to detect chromosomal abnormalities in early embryos.
Research in Down syndrome has the potential to improve the clinical care and quality of life for individuals with Down syndrome and their families. Areas of current and future research activity include the development of clinical trials for testing medical interventions and therapeutics in those with Down syndrome, the development and characterization of mouse models for understanding Down syndrome and testing the effectiveness of various medications, and the exploration of a variety of health systems' research questions.
- Recent studies explore the neurodevelopmental impact of congenital heart defects on people with Down syndrome.
- Based on recent findings, scientists believe that short chromosome 21 telomere length may become a biomarker for early stages of dementia in people with Down syndrome, which currently can be difficult to identify.
- Researchers are assessing ways to improve communication between parents and children with Down syndrome.
- One study is testing a portable electronic device designed to motivate increased physical activity among people with intellectual and developmental disabilities (IDDs) and to monitor their progress.
- Studies focused on reducing an imbalance between excitation and inhibition in the nervous system have provided some evidence of lasting effects.
- Research on choline supplementation during pregnancy has provided evidence of lasting effects on memory and cognition.
- Researchers are exploring ways to predict obstructive sleep apnea in people with Down syndrome.
Future research related to health care disparities and Down syndrome focuses on ways to increase access to medical care and to increase life expectancy, particularly among underrepresented minorities. Another issue that needs to be addressed is the dearth of adult health care providers with expertise to provide appropriate medical care for those with Down syndrome who are now adults. To identify ways to ease the transition between adolescent care for those with Down syndrome and adult lifestyles, the following questions should be considered:
- What are the factors that facilitate and influence successful transition?
- What are the roles of youth and families in the transition process?
- What are the skills and knowledge they need?
- What are the indicators of a successful system for transition?
To achieve its goals related to Down syndrome research, the NICHD supports and participates in a variety of other activities, including NIH-wide efforts. Some of these are listed below.
- The Down Syndrome Consortium, led by the NICHD, brings together stakeholders from public and private groups to advance the exchange of information on Down syndrome research.
- The NICHD leads the NIH Down Syndrome Working Group, which was created to coordinate and advance NIH research on Down syndrome. In 2007, the Working Group met with members of the scientific community and national Down syndrome organizations to discuss gaps in knowledge and the needs of the community. These meetings led to the development of the NIH Research Plan on Down Syndrome (2007). The NIH published its revised plan—Down Syndrome Directions: NIH Research Plan on Down Syndrome (2014)—in November 2014.
- The Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers (EKSIDDRC), established 1 year after the NICHD's founding, provide core infrastructure and research support to 15 centers at universities and children's hospitals throughout the country.
- Brain and Tissue Bank for Developmental Disorders (University of Maryland, Baltimore) is a human tissue repository that systematically collects, stores, and distributes brain and other tissues for research dedicated to the improved understanding, care, and treatment of individuals with IDDs, including Down syndrome.
- The Jackson Laboratory Cytogenetic & Down Syndrome Models Resource maintains and distributes stocks of mouse models for Down syndrome as well as the study of chromosomal aneuploidy.
- Knockout Mouse Project (KOMP) is a trans-NIH initiative that aims to generate a comprehensive and public resource comprised of mouse embryonic stem cells containing a null mutation in every gene in the mouse genome.