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Medical Care for Adults with Down Syndrome

Key Questions Feb 8, 2024
Download the file for this report here.

The Patient-Centered Outcomes Research Institute (PCORI) is partnering with the Agency for Healthcare Research and Quality (AHRQ) to develop a systematic review on Medical Care for Adults with Down syndrome. The Global Down Syndrome Foundation (GLOBAL) plans to use this systematic evidence review to update and expand a related clinical practice guideline.

Down syndrome, a chromosomal condition in which individuals are born with an extra full or partial copy of chromosome 21, is the most prevalent genetic cause of intellectual disability.1 Down syndrome occurs in 1 out of every 700 live births in the United States, a rate that has risen over the past years from 1 in 1,000.2 This means that although an estimated 200,000 individuals with Down syndrome lived in the United States in 2010, adjusting for the rising birthrate suggests the population could far exceed 350,000.3-6 

Down syndrome is characterized by a host of disparate medical, psychological, and social issues beyond intellectual disability, and individuals with Down syndrome face very different risks for many co-occurring health conditions compared with the general population.1 In the case of Alzheimer’s disease, for example, individuals with Down syndrome are at greatly increased risk, with a lifetime risk of up to 90%, and an earlier age of onset and mortality than those without Down syndrome.7,8 The increased risk is also apparent for a number of other conditions including thyroid disease, obstructive sleep apnea, and diabetes.  Conversely, individuals with Down syndrome experience a decreased risk for some other diseases, such as solid tumor malignancies and atherosclerotic cardiovascular disease.3,9,10

The unique health issues and considerations for individuals with Down syndrome pose a challenge to providing high quality, comprehensive medical care throughout their lifespan.  The life expectancy for individuals with Down syndrome has significantly increased from past decades and is now at 60 years of age compared to just 25 years in the 1980’s.  Accordingly, there is an increased need for high quality, long term care (primary and specialty care) to support healthy aging, manage co-occurring conditions, and promote quality of life.1,3,5 However, a lack of funding and underrepresentation of individuals with Down syndrome in research has led to a lack of evidence on how best to manage their health and co-occurring conditions for this population.11

As the number of individuals with Down syndrome grows and life expectancy continues to rise, the need to identify best practices for the medical management of adults with Down syndrome intensifies. In response to this need, the Global Down Syndrome Foundation (GLOBAL) published the 2020 clinical practice guideline, Medical Care for Adults with Down Syndrome, which is recognized as the first evidence-based guideline supporting clinicians caring for adults with Down syndrome.3,12 The guideline is cited by key clinical resources and organizations, including the National Institutes of Health,  the Down Syndrome Medical Interest Group of the United States, the National Down Syndrome Congress, and the National Down Syndrome Society.13-15

The 2020 GLOBAL guideline provides recommendations for screening, diagnosis, and treatment of health conditions across nine clinical areas, identified as critically important for this population by experts and the wider Down syndrome community as part of guideline development: behavioral conditions, dementia, diabetes, cardiovascular disease, obesity, atlantoaxial instability, osteoporosis, thyroid, and celiac disease. The 2020 guideline’s recommendations are based on limited evidence, however, with the guideline’s underlying systematic review including only 22 studies published through 2020.3,12

GLOBAL intends to update and expand the scope of their guideline to include four new clinical topic areas (e.g., sleep apnea, solid tumors, blood cancers/leukemias, and vision) and one considerable addition to the area of musculoskeletal conditions. A new systematic review in support of guideline development is warranted, as evidence has accumulated in the past few years, with many new studies mapping onto the four new clinical areas of interest in addition to the previously identified clinical areas and conditions. Additionally, while a few recent systematic reviews offer insights for specific health conditions in this population, including information on the estimated prevalence of co-occurring conditions like osteopenia and pharmacologic treatments for dementia among adults with Down syndrome, none comprehensively synthesize the evidence for adults with Down syndrome.9,10,16,17

Given the lack of a recent and comprehensive systematic review in the face of accumulating evidence, this proposed systematic review will aim to inform the update and expansion of the GLOBAL guideline on medical care for adults with Down syndrome in order to inform decision-making for physicians, patients, and caregivers. The review will specifically address care for conditions commonly associated with Down syndrome that occur at increased risk or decreased risk among adults with Down syndrome. 9,10,18

KQ1. What are the benefits, and harms, of screening for conditions occurring at increased or decreased prevalence in adults with Down syndrome?

       KQ1a. Do adults with Down syndrome require a different approach to preventive screening (different screening timing/frequency/interval, or different instruments) than the general adult population?

KQ2. What are the benefits, and harms of diagnostic approaches for conditions occurring at increased or decreased prevalence in adults with Down syndrome?

KQ3. What are the benefits and harms of interventions to treat conditions occurring at increased or decreased prevalence in adults with Down syndrome?

Contextual Questions

CQ1. What is the prevalence of conditions occurring more frequently in adults with Down syndrome compared to the general population and how does this vary by age/decade of age, gender, setting (rural) and race/ethnicity?  

CQ2. How do clinical symptoms and the presentation of common mental health conditions such as anxiety and depression differ among adults with Down Syndrome compared to their presentation in the general adult population?

Table 1: Key Questions and PICOs for Medical Care for Adults with Down Syndrome

Key Questions

Population

Intervention

Comparator

Outcomes

KQ1. What are the benefits, harms of screening approaches for conditions occurring at increased prevalence in adults with Down syndrome?

KQ1a. Do adults with Down syndrome require a different screening timing/frequency interval, or a different approach or instrument than the general population?

Adults with Down syndrome

Screening for conditions occurring at increased prevalence for adults with Down syndrome

For all conditions, compared with no screening or alternative approach to screening

Standard recommended screening approach for adults (non-pregnant)

  • Benefits: accurate diagnosis, time to diagnosis or intervention
  • Harms: adverse events related to screening

KQ2. What are the benefits, harms of diagnostic approaches for conditions occurring at increased prevalence in adults with Down syndrome?

Adults with Down syndrome

Diagnostic approach/(es) for conditions associated with Down syndrome (non-pregnant)

For all conditions, compared with no diagnostic approach or alternative approach to diagnosis

  • Benefits: Time to intervention/treatment
  • Health and quality of life outcomes
  • Harms: Misdiagnosis/adverse effects of diagnosis

KQ3. What are the benefits and harms of interventions to treat conditions occurring at increased prevalence in adults with Down syndrome?

Adults with Down syndrome

Treatment approach/(es) for adults with Down syndrome-associated conditions

For all conditions, compared with usual care or

alternative approach to treatment

Intermediate outcomes

  • Treatment adherence
  • Change in standardized symptom measures
  • Lab values
  • Adverse treatment effects

Final outcomes

  • Morbidity/mortality (e.g., Years of life saved)
  • Quality of life
  • Functional outcomes (e.g., Activities of daily living, assisted living/nursing home status)
  • Caregiver or family outcomes (including caregiver health and quality of life)

Figure 1. Preliminary Analytic Framework – Medical Care for Adults with Down Syndrome

Figure 1 shows the preliminary analytic framework for the review on the medical care of adults with Down syndrome.  The framework is represented as a series of boxes joined by arrows that indicate the three key questions on screening, diagnosis and treatment of adults with Down syndrome within the context of the PICOTs shown in Table 2.  The box on the far left indicates the patient population: adults with Down syndrome.  Moving to the right, the next box indicates outcomes for Key Question 1 on screening.  Outcomes include the early identification of the target condition and the adverse effects of screening.  The next box indicates the outcomes for Key Question 2 on diagnosis.  These outcomes include the diagnosis of the target condition, time to diagnosis or treatment as well as the adverse effects of diagnosis.  The next box indicates the range of interventions for Key Question 3 on treatment which include pharmacologic, non-pharmacologic, surgical and psychosocial interventions appropriate for the particular target conditions.  The last 2 boxes indicate intermediate and final outcomes for the population such as treatment adherence (intermediate) and morbidity and mortality, quality of life and caregiver outcomes (final).

  1. Bull MJ. Down Syndrome. N Engl J Med. 2020 Jun 11;382(24):2344-2352. doi: 10.1056/NEJMra1706537. PMID: 32521135.
  2. Mai CT, Isenburg JL, Canfield MA, Meyer RE, Correa A, Alverson CJ, Lupo PJ, Riehle-Colarusso T, Cho SJ, Aggarwal D, Kirby RS; National Birth Defects Prevention Network. National population-based estimates for major birth defects, 2010-2014. Birth Defects Res. 2019 Nov 1;111(18):1420-1435. doi: 10.1002/bdr2.1589. Epub 2019 Oct 3. PMID: 31580536; PMCID: PMC7203968.
  3. The Global Down Syndrome Foundation (GLOBAL) Medical Care Guidelines for Adults with Down Syndrome. 2020.
  4. Parker SE, Mai CT, Canfield MA, et al. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol. Dec 2010;88(12):1008-16. doi:10.1002/bdra.20735
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  6. de Graaf G, Buckley F, Skotko BG. Estimation of the number of people with Down syndrome in the United States. Genetics in Medicine. Sep 08 2017:439-447. doi:10.1038/gim.2016.127
  7. Lott IT, Dierssen M. Cognitive deficits and associated neurological complications in individuals with Down's syndrome. Lancet Neurol. 2010 Jun;9(6):623-33. doi: 10.1016/S1474-4422(10)70112-5. PMID: 20494326.
  8. Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M. Alzheimer's disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 2021 Nov;20(11):930-942. doi: 10.1016/S1474-4422(21)00245-3. PMID: 34687637; PMCID: PMC9387748.
  9. Capone GT, Chicoine B, Bulova P, Stephens M, Hart S, Crissman B, Videlefsky A, Myers K, Roizen N, Esbensen A, Peterson M, Santoro S, Woodward J, Martin B, Smith D; Down Syndrome Medical Interest Group DSMIG-USA Adult Health Care Workgroup. Co-occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Am J Med Genet A. 2018 Jan;176(1):116-133. doi: 10.1002/ajmg.a.38512. Epub 2017 Nov 12. PMID: 29130597.
  10. Capone G, Stephens M, Santoro S, Chicoine B, Bulova P, Peterson M, Jasien J, Smith AJ; Down Syndrome Medical Interest Group (DSMIG-USA) Adult Health Workgroup. Co-occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Part II. Am J Med Genet A. 2020 Jul;182(7):1832-1845. doi: 10.1002/ajmg.a.61604. Epub 2020 Apr 27. PMID: 32338447.
  11. Hendrix JA, Amon A, Abbeduto L, Agiovlasitis S, Alsaied T, Anderson HA, Bain LJ, Baumer N, Bhattacharyya A, Bogunovic D, Botteron KN, Capone G, Chandan P, Chase I, Chicoine B, Cieuta-Walti C, DeRuisseau LR, Durand S, Esbensen A, Fortea J, Giménez S, Granholm AC, Hahn LJ, Head E, Hillerstrom H, Jacola LM, Janicki MP, Jasien JM, Kamer AR, Kent RD, Khor B, Lawrence JB, Lemonnier C, Lewanda AF, Mobley W, Moore PE, Nelson LP, Oreskovic NM, Osorio RS, Patterson D, Rasmussen SA, Reeves RH, Roizen N, Santoro S, Sherman SL, Talib N, Tapia IE, Walsh KM, Warren SF, White AN, Wong GW, Yi JS. Opportunities, barriers, and recommendations in down syndrome research. Transl Sci Rare Dis. 2021;5(3-4):99-129. doi: 10.3233/trd-200090. Epub 2021 Apr 15. PMID: 34268067; PMCID: PMC8279178.
  12. Tsou AY, Bulova P, Capone G, et al. Medical Care of Adults With Down Syndrome: A Clinical Guideline. JAMA. 2020;324(15):1543–1556. doi:10.1001/jama.2020.17024
  13. UpToDate. Society guideline links: Down syndrome.
  14. The National Down Syndrome Society. Healthcare Guidelines.
  15. Down Syndrome Medical Interest Group-USA. Health Care Resources for Adults. Available from: DSMIG Resources (dsmig-usa.org)
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  18. Baumer NT, Hojlo MA, Pawlowski KG, Milliken AL, Lombardo AM, Sargado S, et al. Co-occurring conditions in Down syndrome: Findings from a clinical database. Am J Med Genet C Semin Med Genet. 2023:e32072.

Project Timeline

Medical Care for Adults with Down Syndrome

Feb 7, 2024
Topic Initiated
Feb 8, 2024
Key Questions
Feb 8, 2024 - Feb 29, 2024
Page last reviewed February 2024
Page originally created February 2024

Internet Citation: Key Questions: Medical Care for Adults with Down Syndrome. Content last reviewed February 2024. Effective Health Care Program, Agency for Healthcare Research and Quality, Rockville, MD.
https://effectivehealthcare.ahrq.gov/products/care-adults-down-syndrome

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