NICHD Down Syndrome Research Information

NICHD has a long history of conducting and supporting research on Down syndrome and related disorders. When the institute was established in 1962, one of its primary charges was to encourage investigations on human development throughout the lifespan, with an emphasis on understanding intellectual and developmental disabilities, including Down syndrome.

Since then, researchers have explored the chromosomal causes of the syndrome, created animal models to test interventions, assessed long-term outcomes for people living with the syndrome, and addressed many other biomedical and behavioral topics.

NIH published its revised plan—Down Syndrome Directions: NIH Research Plan on Down Syndrome (2014)—in November 2014. NICHD is working to update the content on this page to reflect the revised Research Plan.

Many of NICHD’s goals for research on Down syndrome align with topic areas described in the NIH Research Plan on Down Syndrome (2007). The institute played a lead role in developing the Research Plan as part of the trans-NIH Working Group on Down Syndrome, which aims to build on the existing research foundation and coordinate Down syndrome research at NIH. The following are some of the goals from the Research Plan.

• Causes, pathophysiology, and disease progression. Topics include aging and Down syndrome, the effect of cellular and molecular processes on symptoms, and cognitive functioning in model mice.
• Diagnosis, screening, and functional measures. Goals in this area include improved characterization of Down syndrome phenotypes, investigation of measures of cognitive function throughout the lifespan, and better linkage between human and mouse studies.
• Treatment. This topic area includes testing orphan drugs, measuring the impact of early intervention on cognitive development, and using Alzheimer’s disease research to inform potential therapeutics.
• Comorbid medical and psychiatric conditions. Research explores treatment and management of such conditions as leukemia, congenital heart disease, and dementia.
• Living with Down syndrome. Studies cover a broad range of issues, such as tracking real-world outcomes for families living with Down syndrome, health disparities in access to care, and interventions for transitional stages.
• Research infrastructure. Efforts include promoting the inclusion of people with Down syndrome in a range of NIH-sponsored clinical trials, building tissue and brain banks, and improving the availability of animal models.

In addition, NICHD is a leading and active member of the Down Syndrome Consortium, a public–private partnership created to foster information exchange on biomedical and biobehavioral research on Down syndrome. The Consortium’s activities include implementing the Research Plan and establishing a Down syndrome registry.

The institute’s portfolio covers a broad range of research areas, including the causes, treatment, and prevention of Down syndrome.

New NIH Initiative: NICHD is pleased to be part of INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE), an NIH-wide initiative that launched in June 2018 in support of a congressional directive in the fiscal year 2018 Omnibus Appropriations. The project aims to understand critical health and quality-of-life needs for individuals with Down syndrome, with the goal of yielding scientific discoveries to improve the health, well-being, and neurodevelopment of individuals with Down syndrome, as well as their risk and resilience for common diseases that they share with individuals who do not have Down syndrome. INCLUDE will investigate conditions that affect individuals with Down syndrome and the general population, such as Alzheimer’s disease/dementia, autism, cataracts, celiac disease, congenital heart disease, and diabetes.

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 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 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 Cytogenetic and Down Syndrome Models Resource , a distribution center supported by 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 are currently 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 when they administered neuroprotective peptides (small protein subunits) to mice before birth, the mice performed 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 untreated mice did. In this earlier study, the researchers examined developmental milestones for sensory, motor skill, and muscle tone in the first 3 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. 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 Congenital Anomalies 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) to understand the mechanisms that lead to chromosome missegregation, which can cause Down syndrome and other disorders.
• In addition, 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.

For example:

• 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 IDDs and 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 and adult care for those with Down syndrome, 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?

Other Activities and Advances

To achieve its goals related to Down syndrome research, NICHD supports and participates in a variety of other activities, including NIH-wide efforts. Some of these are listed in the following section.

• The Down Syndrome Consortium, led by NICHD, brings together stakeholders from public and private groups to advance the exchange of information on Down syndrome research.
• 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). NIH published its revised plan—Down Syndrome Directions: NIH Research Plan on Down Syndrome (2014)—in November 2014.
• The Eunice Kennedy Shriver Intellectual & Developmental Disabilities Research Centers (EKS-IDDRCs), established the year after NICHD’s founding, provide core infrastructure and research support to 15 centers at universities and children’s hospitals throughout the country.
• The University of Maryland Brain and Tissue Bank 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 and Down Syndrome Models Resource maintains and distributes stocks of mouse models for Down syndrome as well as the study of chromosomal aneuploidy.
• The Knockout Mouse Phenotyping Program (KOMP2) is a trans-NIH initiative that aims to generate a comprehensive and public resource composed of mouse embryonic stem cells containing a null mutation in every gene in the mouse genome.