PARTNERS-DS Course 1 Through the Lifespan

Friday, September 4, 2026, 12:01 AM - Sunday, September 3, 2028, 11:59 PM


Advance your clinical research journey with PARTNERS-DS, a short course built for early career investigators passionate about improving the lives of people with Down syndrome. Learn from experienced researchers and community partners to strengthen your skills, deepen your understanding, and spark innovative, collaborative research. This online component is meant to be an introduction to the content and can be complimented by the in-person course or taken alone. The modules in this course are intended to broaden investigators’ understanding of common co-occurring conditions from infancy through adulthood, highlighting the impact across organ systems. This course is designed to equip DS researchers with a comprehensive, lifespan-oriented perspective that strengthens study design, outcome selection, and enhance opportunities for interdisciplinary collaboration.

1. Explain the genetic basis and prevalence of Down syndrome
2. Identify common physical, developmental, and behavioral features associated with Down syndrome
3. Describe the neurodevelopmental profile including learning and behavior
4. Discuss current trends in health outcomes, quality of life and life expectancy for individuals with Down syndrome
5. Describe common congenital medical conditions associated with Down syndrome, including congenital heart disease and gastrointestinal anomalies
6. Explain the origin of common gastrointestinal issues in infancy and early childhood and the relation to the enteric nervous system
7. Recognize the prevalence, clinical features, and implications of sleep apnea in young children with Down syndrome
8. Identify common ocular and hearing concerns and the importance and impact of early detection
9. Describe the underlying immune mechanisms and increased risk for conditions such as autoimmune thyroid disease, type 1 diabetes, celiac disease, alopecia areata, and hidradenitis suppurativa
10. Understand growth patterns specific to Down syndrome and apply appropriate Down syndrome specific growth charts
11. Discuss pubertal considerations in Down syndrome including timing, approach to examination and opportunity for self-examination in research
12. Discuss menstrual concerns and considerations in Down syndrome including menstrual management, amenorrhea and gonadal failure
13. Describe reproductive health and safety considerations
14. Describe the increased risk of early Alzheimer’s disease and dementia emphasizing early clinical signs and outline available screening tools

Accreditation Statements

Launch Date: 9/4/2026

Expiration Date: 9/3/2028

In support of improving patient care, this activity has been planned and implemented by Indiana University School of Medicine. Indiana University School of Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physicians

Indiana University School of Medicine designates this enduring activity for a maximum of 4.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Psychology (APA)

Continuing Education (CE) credits for psychologists are provided through the co-sponsorship of the American Psychological Association (APA) Office of Continuing Education in Psychology (CEP). The APA CEP Office maintains responsibility for the content of the programs. This activity offers 4.0 continuing education credits for psychologists. 

Disclosure Summary

Indiana University School of Medicine (IUSM) policy ensures that those who have influenced the content of a CE activity (e.g. planners, faculty, authors, reviewers and others) disclose all financial relationships with any ineligible companies so that IUSM may identify and mitigate any conflicts of interest prior to the activity. All educational programs sponsored by Indiana University School of Medicine must demonstrate balance, independence, objectivity, and scientific rigor. 

There are no relevant financial relationship(s) with ineligible companies for anyone who was in control of the content of this activity, except: 

Sheela Magge has disclosed Membership, Data Monitoring Committee from LILLY USA, LLC. 

Robert Heuckroth has disclosed Scientific Advisory Board Member from Neurenati Therapeutics and owning stock from  Astrazeneca, CRISPR, Eli Lilly & Co, Moderna Inc, Pfizer and Vertex Pharmaceuticals.

Hillary Snapp has disclosed Consultant/ Advisory Board Member from Cochlear Americas, Corp as well as a Grant Recipient from MED-EL, Corp and RestorEar.

All of the relevant financial relationships listed for these individuals have been mitigated. 

Sigan Hartley has disclosed Consultant from Alnylam Pharmaceuticals, INC. and Ionis Pharmaceuticals, Inc. Both relationships have ended.

An ineligible company is any entity whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients. 

 

The activity evaluation is required for credit. Credit will be awarded within 60 days following the activity. A transcript with proof of your participation will be emailed to you for this IUSM activity. For questions and concerns, please contact special project manager, Breann Bauer at [email protected]. 

REFERENCES:

Module 1

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2. al GNe. Down Syndrome and Aging and Epigenetics. Chapter 7: Biochemistry and Cell Biology of Aging Part II.

3. Allyse M, Minear MA, Berson E, et al. Non-invasive prenatal testing: a review of international implementation and challenges. Int J Womens Health. 2015;7:113–26. doi:10.2147/IJWH.S67124

4. Antonarakis SE. Down syndrome and the complexity of genome dosage imbalance. Nat Rev Genet. Mar 2017;18(3): 147–163. doi:10.1038/nrg.2016.154

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6. Antonarakis SE, Skotko BG, Rafii MS, et al. Down syndrome. Nat Rev Dis Primers. Feb 6 2020;6(1):9. doi:10.1038/s41572-019-0143-7

7. Badia M, Orgaz BM, Verdugo MA, Ullan AM, Martinez MM. Personal factors and perceived barriers to participation in leisure activities for young and adults with developmental disabilities. Res Dev Disabil. Nov–Dec 2011;32(6):2055–63. doi:10.1016/j.ridd.2011.08.007

8. Basil JS, Santoro SL, Martin LJ, Healy KW, Chini BA, Saal HM. Retrospective Study of Obesity in Children with Down Syndrome. J Pediatr. Jun 2016;173:143–8. doi:10.1016/j.jpeds.2016.02.046

9. Bertapelli F, Pitetti K, Agiovlasitis S, Guerra-Junior G. Overweight and obesity in children and adolescents with Down syndrome-prevalence, determinants, consequences, and interventions: A literature review. Res Dev Disabil. Oct 2016;57:181–92. doi:10.1016/j.ridd.2016.06.018

10. Book JA, Fraccaro M, Lindsten J. Cytogenetical observations in mongolism. Acta Paediatr (Stockh). Sep 1959;48:453–68. doi:10.1111/j.1651-2227.1959.tb16409.x

11. Bull MJ. Down Syndrome. N Engl J Med. Jun 11 2020;382(24):2344–2352. doi:10.1056/NEJMra1706537

12. Bull MJ, Trotter T, Santoro SL, et al. Health Supervision for Children and Adolescents With Down Syndrome. Pediatrics. May 1 2022;149(5)doi:10.1542/peds.2022-057010

13. Chen CJJ, Ringenbach SDR. Walking performance in adolescents and young adults with Down syndrome: the role of obesity and sleep problems. J Intellect Disabil Res. Apr 2018;62(4):339–348. doi:10.1111/jir.12474

14. Chicoine B, Rivelli A, Fitzpatrick V, Chicoine L, Jia G, Rzhetsky A. Prevalence of Common Disease Conditions in a Large Cohort of Individuals With Down Syndrome in the United States. J Patient Cent Res Rev. Spring 2021;8(2):86–97. doi:10.17294/2330-0698.1824

15. de Graaf G, Buckley F, Skotko BG. Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States. Am J Med Genet A. Apr 2015;167A(4):756–67. doi:10.1002/ajmg.a.37001

16. de Graaf G, Buckley F, Skotko BG. Estimation of the number of people with Down syndrome in Latin America and the Caribbean. Genet Med. Jan 2026;28(1):101621. doi:10.1016/j.gim.2025.101621

17. Devlin L, Morrison PJ. Mosaic Down's syndrome prevalence in a complete population study. Arch Dis Child. Dec 2004;89(12):1177–8. doi:10.1136/adc.2003.031765

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19. Englund A, Jonsson B, Zander CS, Gustafsson J, Anneren G. Changes in mortality and causes of death in the Swedish Down syndrome population. Am J Med Genet A. Apr 2013;161A(4):642–9. doi:10.1002/ajmg.a.35706

20. Ghaziuddin M. Autism in Down's syndrome: a family history study. J Intellect Disabil Res. Oct 2000;44 ( Pt 5):562–6. doi:10.1046/j.1365-2788.2000.00271.x

21. Ghaziuddin N, Nassiri A, Miles JH. Catatonia in Down syndrome; a treatable cause of regression. Neuropsychiatr Dis Treat. 2015;11:941–9. doi:10.2147/NDT.S77307

22. Grieco J, Pulsifer M, Seligsohn K, Skotko B, Schwartz A. Down syndrome: Cognitive and behavioral functioning across the lifespan. Am J Med Genet C Semin Med Genet. Jun 2015;169(2):135–49. doi:10.1002/ajmg.c.31439

23. Hamburg S, Lowe B, Startin CM, et al. Assessing general cognitive and adaptive abilities in adults with Down syndrome: a systematic review. J Neurodev Disord. Aug 30 2019;11(1):20. doi:10.1186/s11689-019-9279-8

24. Hamerton JL, Giannelli F, Polani PE. Cytogenetics of Down's Syndrome (Mongolism). I. Data on a Consecutive Series of Patients Referred for Genetic Counselling and Diagnosis. Cytogenetics. 1965;4:171–85. doi:10.1159/000129853

25. Hart SA, Nandi D, Backes CH, Cua CL. Impact of prenatal screening on congenital heart defects in neonates with Down syndrome in the US. Pediatr Res. Nov 2021;90(5):1081–1085. doi:10.1038/s41390-021-01416-7

26. Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. Apr 2001;2(4):280–91. doi:10.1038/35066065

27. Hepburn S, Philofsky A, Fidler DJ, Rogers S. Autism symptoms in toddlers with Down syndrome: a descriptive study. J Appl Res Intellect Disabil. Jan 2008;21(1):48–57. doi:10.1111/j.1468-3148.2007.00368.x

28. Hill M, Barrett A, Choolani M, Lewis C, Fisher J, Chitty LS. Has noninvasive prenatal testing impacted termination of pregnancy and live birth rates of infants with Down syndrome? Prenat Diagn. Dec 2017;37(13):1281–1290. doi:10.1002/pd.5182

29. Hithersay R, Startin CM, Hamburg S, et al. Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years. JAMA Neurol. Feb 1 2019;76(2):152–160. doi:10.1001/jamaneurol.2018.3616

30. Jacobs PA, Baikie AG, Court Brown WM, Strong JA. The somatic chromosomes in mongolism. Lancet. Apr 4 1959;1(7075):710. doi:10.1016/s0140-6736(59)91892-6

31. Kent RD, Vorperian HK. Speech impairment in Down syndrome: a review. J Speech Lang Hear Res. Feb 2013;56(1):178–210. doi:10.1044/1092-4388(2012/12-0148)

32. Kinnear D, Morrison J, Allan L, Henderson A, Smiley E, Cooper SA. Prevalence of physical conditions and multimorbidity in a cohort of adults with intellectual disabilities with and without Down syndrome: cross-sectional study. BMJ Open. Feb 5 2018;8(2):e018292. doi:10.1136/bmjopen-2017-018292

33. Korenberg JR, Chen XN, Schipper R, et al. Down syndrome phenotypes: the consequences of chromosomal imbalance. Proc Natl Acad Sci U S A. May 24 1994;91(11):4997–5001. doi:10.1073/pnas.91.11.4997

34. Kruszka P, Porras AR, Sobering AK, et al. Down syndrome in diverse populations. Am J Med Genet A. Jan 2017;173(1):42–53. doi:10.1002/ajmg.a.38043

35. Kumin L. Speech intelligibility and childhood verbal apraxia in children with Down syndrome. Downs Syndr Res Pract. Jul 2006;10(1):10–22. doi:10.3104/reports.301

36. Lejeune J, Gautier M, Turpin R. [Study of somatic chromosomes from 9 mongoloid children]. C R Hebd Seances Acad Sci. Mar 16 1959;248(11):1721–2. Étude des chromosomes somatiques de neuf enfants mongoliens. 

37. Lemons CJ, Powell SR, King SA, Davidson KA. Mathematics interventions for children and adolescents with Down syndrome: a research synthesis. J Intellect Disabil Res. Aug 2015;59(8):767–83. doi:10.1111/jir.12188

38. Lukowski AF, Milojevich HM, Eales L. Cognitive Functioning in Children with Down Syndrome: Current Knowledge and Future Directions. Adv Child Dev Behav. 2019;56:257–289. doi:10.1016/bs.acdb.2019.01.002

39. Mai CT, Isenburg JL, Canfield MA, et al. National population-based estimates for major birth defects, 2010-2014. Birth Defects Res. Nov 1 2019;111(18):1420–1435. doi:10.1002/bdr2.1589

40. Marderstein AR, De Zuani M, Moeller R, et al. Single-cell multi-omics map of human fetal blood in Down syndrome. Nature. Oct 2024;634(8032):104–112. doi:10.1038/s41586-024-07946-4

41. Martin GE, Klusek J, Estigarribia B, Roberts JE. Language Characteristics of Individuals with Down Syndrome. Top Lang Disord. Apr 2009;29(2):112–132. doi:10.1097/tld.0b013e3181a71fe1

42. Mihaila I, Handen BL, Christian BT, Hartley SL. Leisure activity in middle-aged adults with Down syndrome: Initiators, social partners, settings and barriers. J Appl Res Intellect Disabil. Sep 2020;33(5):865–875. doi:10.1111/jar.12706

43. Mihaila I, Hartley SL, Handen BL, et al. Leisure Activity and Caregiver Involvement in Middle-Aged and Older Adults With Down Syndrome. Intellect Dev Disabil. Apr 2017;55(2):97–109. doi:10.1352/1934-9556-55.2.97

44. Mikkelsen M. Down syndrome: cytogenetic epidemiology. Hereditas. 1977;86(1):45–50. doi:10.1111/j.1601-5223.1977.tb01211.x

45. Miles JH, Takahashi N, Muckerman J, Nowell KP, Ithman M. Catatonia in Down syndrome: systematic approach to diagnosis, treatment and outcome assessment based on a case series of seven patients. Neuropsychiatr Dis Treat. 2019;15:2723–2741. doi:10.2147/NDT.S210613

46. Morris JK, Alberman E, Mutton D, Jacobs P. Cytogenetic and epidemiological findings in Down syndrome: England and Wales 1989-2009. Am J Med Genet A. May 2012;158A(5):1151–7. doi:10.1002/ajmg.a.35248

47. Morris JK, Garne E, Wellesley D, et al. Major congenital anomalies in babies born with Down syndrome: a EUROCAT population-based registry study. Am J Med Genet A. Dec 2014;164A(12):2979–86. doi:10.1002/ajmg.a.36780

48. Morris JK, Wald NJ, Mutton DE, Alberman E. Comparison of models of maternal age-specific risk for Down syndrome live births. Prenat Diagn. Mar 2003;23(3):252–8. doi:10.1002/pd.568

49. Mutton D, Alberman E, Hook EB. Cytogenetic and epidemiological findings in Down syndrome, England and Wales 1989 to 1993. National Down Syndrome Cytogenetic Register and the Association of Clinical Cytogeneticists. J Med Genet. May 1996;33(5):387–94. doi:10.1136/jmg.33.5.387

50. Naess KA, Lyster SA, Hulme C, Melby-Lervag M. Language and verbal short-term memory skills in children with Down syndrome: a meta-analytic review. Res Dev Disabil. Nov–Dec 2011;32(6):2225–34. doi:10.1016/j.ridd.2011.05.014

51. Naess KA, Melby-Lervag M, Hulme C, Lyster SA. Reading skills in children with Down syndrome: a meta-analytic review. Res Dev Disabil. Mar–Apr 2012;33(2):737–47. doi:10.1016/j.ridd.2011.09.019

52. Neil N, Jones EA. Communication intervention for individuals with Down syndrome: Systematic review and meta-analysis. Dev Neurorehabil. Jan 2018;21(1):1–12. doi:10.1080/17518423.2016.1212947

53. Niikawa N, Kajii T. The origin of mosaic Down syndrome: four cases with chromosome markers. Am J Hum Genet. Jan 1984;36(1):123–30. 

54. Olson LE, Richtsmeier JT, Leszl J, Reeves RH. A chromosome 21 critical region does not cause specific Down syndrome phenotypes. Science. Oct 22 2004;306(5696):687–90. doi:10.1126/science.1098992

55. Oxelgren UW, Myrelid A, Anneren G, et al. Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study. Dev Med Child Neurol. Mar 2017;59(3):276–283. doi:10.1111/dmcn.13217

56. Palumbo ML, McDougle CJ. Pharmacotherapy of Down syndrome. Expert Opin Pharmacother. Dec 2018;19(17):1875–1889. doi:10.1080/14656566.2018.1529167

57. Pangalos C, Avramopoulos D, Blouin JL, et al. Understanding the mechanism(s) of mosaic trisomy 21 by using DNA polymorphism analysis. Am J Hum Genet. Mar 1994;54(3):473–81. 

58. Patterson T, Rapsey CM, Glue P. Systematic review of cognitive development across childhood in Down syndrome: implications for treatment interventions. J Intellect Disabil Res. Apr 2013;57(4):306–18. doi:10.1111/jir.12037

59. Pelleri MC, Locatelli C, Mattina T, et al. Partial trisomy 21 with or without highly restricted Down syndrome critical region (HR-DSCR): report of two new cases and reanalysis of the genotype-phenotype association. BMC Med Genomics. Dec 21 2022;15(1):266. doi:10.1186/s12920-022-01422-6

60. Pfitzer C, Helm PC, Rosenthal LM, Berger F, Bauer UMM, Schmitt KR. Dynamics in prevalence of Down syndrome in children with congenital heart disease. Eur J Pediatr. Jan 2018;177(1):107–115. doi:10.1007/s00431-017-3041-6

61. Presson AP, Partyka G, Jensen KM, et al. Current estimate of Down Syndrome population prevalence in the United States. J Pediatr. Oct 2013;163(4):1163–8. doi:10.1016/j.jpeds.2013.06.013

62. Pueschel SM RJ. Down syndrome: advances in biomedicine and the behavioral sciences. 1982;

63. Rafii MS, Santoro SL. Prevalence and Severity of Alzheimer Disease in Individuals With Down Syndrome. JAMA Neurol. Feb 1 2019;76(2):142–143. doi:10.1001/jamaneurol.2018.3443

64. Real de Asua D, Quero M, Moldenhauer F, Suarez C. Clinical profile and main comorbidities of Spanish adults with Down syndrome. Eur J Intern Med. Jul 2015;26(6):385–91. doi:10.1016/j.ejim.2015.05.003

65. Richards BW. Mosaic mongolism. J Ment Defic Res. Mar 1969;13(1):66–83. doi:10.1111/j.1365-2788.1969.tb01067.x

66. Roche M, Mircher C, Toulas J, et al. Efficacy and safety of methylphenidate on attention deficit hyperactivity disorder in children with Down syndrome. J Intellect Disabil Res. Aug 2021;65(8):795–800. doi:10.1111/jir.12832

67. Rubenstein E, Toth M, Tewolde S. Autism Among Adults with Down Syndrome: Prevalence, Medicaid Usage, and Co-Occurring Conditions. J Autism Dev Disord. Oct 2025;55(10):3670–3677. doi:10.1007/s10803-024-06484-2

68. Sanchez Moreno B, Adan-Lirola L, Rubio-Serrano J, Real de Asua D. Causes of mortality among adults with Down syndrome before and after the COVID-19 pandemic in Spain. J Intellect Disabil Res. Feb 2024;68(2):128–139. doi:10.1111/jir.13096

69. Santoro JD, Patel L, Kammeyer R, et al. Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus. Front Neurol. 2022;13:940175. doi:10.3389/fneur.2022.940175

70. Sevde Afife Ersoy HAGaFHÇ. Psychopathology in Down Syndrome. 2018;

71. Shaffer LG, Jackson-Cook CK, Stasiowski BA, Spence JE, Brown JA. Parental origin determination in thirty de novo Robertsonian translocations. Am J Med Genet. Aug 1 1992;43(6):957–63. doi:10.1002/ajmg.1320430611

72. Sheets KB, Crissman BG, Feist CD, et al. Practice guidelines for communicating a prenatal or postnatal diagnosis of Down syndrome: recommendations of the national society of genetic counselors. J Genet Couns. Oct 2011;20(5):432–41. doi:10.1007/s10897-011-9375-8

73. Shin M, Besser LM, Kucik JE, et al. Prevalence of Down syndrome among children and adolescents in 10 regions of the United States. Pediatrics. Dec 2009;124(6):1565–71. doi:10.1542/peds.2009-0745

74. Shin M, Siffel C, Correa A. Survival of children with mosaic Down syndrome. Am J Med Genet A. Mar 2010;152A(3):800–1. doi:10.1002/ajmg.a.33295

75. Skotko BG. With new prenatal testing, will babies with Down syndrome slowly disappear? Arch Dis Child. Nov 2009;94(11):823–6. doi:10.1136/adc.2009.166017

76. Smith BA, Ulrich BD. Early onset of stabilizing strategies for gait and obstacles: older adults with Down syndrome. Gait Posture. Oct 2008;28(3):448–55. doi:10.1016/j.gaitpost.2008.02.002

77. Smith E, Hokstad S, Naess KB. Children with Down syndrome can benefit from language interventions; Results from a systematic review and meta-analysis. J Commun Disord. May–Jun 2020;85:105992. doi:10.1016/j.jcomdis.2020.105992

78. Srasuebkul P, Trofimovs J, Trollor J. Life expectancy of people with intellectual disability: a retrospective cohort study from New South Wales, Australia. BMJ Open. Feb 4 2026;16(2):e110184. doi:10.1136/bmjopen-2025-110184

79. Stagni F, Giacomini A, Emili M, Guidi S, Bartesaghi R. Neurogenesis impairment: An early developmental defect in Down syndrome. Free Radic Biol Med. Jan 2018;114:15–32. doi:10.1016/j.freeradbiomed.2017.07.026

80. Stallings EB, Isenburg JL, Rutkowski RE, et al. National population-based estimates for major birth defects, 2016-2020. Birth Defects Res. Jan 2024;116(1):e2301. doi:10.1002/bdr2.2301

81. Ting CH, Rahman MM, Chen YY, et al. Employment of people with Down syndrome: A scoping review. Narra J. Dec 2024;4(3):e1431. doi:10.52225/narra.v4i3.1431

82. Tsou AY, Bulova P, Capone G, et al. Medical Care of Adults With Down Syndrome: A Clinical Guideline. JAMA. Oct 20 2020;324(15):1543–1556. doi:10.1001/jama.2020.17024

83. Vicari S, Bellucci S, Carlesimo GA. Implicit and explicit memory: a functional dissociation in persons with Down syndrome. Neuropsychologia. 2000;38(3):240–51. doi:10.1016/s0028-3932(99)00081-0

84. Walker JC, Dosen A, Buitelaar JK, Janzing JG. Depression in Down syndrome: a review of the literature. Res Dev Disabil. Sep–Oct 2011;32(5):1432–40. doi:10.1016/j.ridd.2011.02.010

85. Warsof SL, Larion S, Abuhamad AZ. Overview of the impact of noninvasive prenatal testing on diagnostic procedures. Prenat Diagn. Oct 2015;35(10):972–9. doi:10.1002/pd.4601

86. Weijerman ME, de Winter JP. Clinical practice. The care of children with Down syndrome. Eur J Pediatr. Dec 2010;169(12):1445–52. doi:10.1007/s00431-010-1253-0

87. Wester Oxelgren U, Aberg M, Myrelid A, et al. Autism needs to be considered in children with Down Syndrome. Acta Paediatr. Nov 2019;108(11):2019–2026. doi:10.1111/apa.14850

88. Wilson EM, Abbeduto L, Camarata SM, Shriberg LD. Estimates of the prevalence of speech and motor speech disorders in adolescents with Down syndrome. Clin Linguist Phon. 2019;33(8):772–789. doi:10.1080/02699206.2019.1595735

89. Yang Q, Rasmussen SA, Friedman JM. Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet. Mar 23 2002;359(9311):1019–25. doi:10.1016/s0140-6736(02)08092-3

90. Yang Y, Conners FA, Merrill EC. Visuo-spatial ability in individuals with Down syndrome: is it really a strength? Res Dev Disabil. Jul 2014;35(7):1473–500. doi:10.1016/j.ridd.2014.04.002

91. Zhu JL, Obel C, Hasle H, Rasmussen SA, Li J, Olsen J. Social conditions for people with Down syndrome: a register-based cohort study in Denmark. Am J Med Genet A. Jan 2014;164A(1):36–41. doi:10.1002/ajmg.a.36272

Module 2

1. Freeman SB, Taft LF, Dooley KJ, et al. Population-based study of congenital heart defects in Down syndrome. Am J Med Genet. Nov 16 1998;80(3):213–7. 

2. Irving CA, Chaudhari MP. Cardiovascular abnormalities in Down's syndrome: spectrum, management and survival over 22 years. Arch Dis Child. Apr 2012;97(4):326–30. doi:10.1136/adc.2010.210534

3. Vis JC, Duffels MG, Winter MM, et al. Down syndrome: a cardiovascular perspective. J Intellect Disabil Res. May 2009;53(5):419–25. doi:10.1111/j.1365-2788.2009.01158.x

4. Bergstrom S, Carr H, Petersson G, et al. Trends in Congenital Heart Defects in Infants With Down Syndrome. Pediatrics. Jul 2016;138(1)doi:10.1542/peds.2016-0123

5. van Velzen CL, Clur SA, Rijlaarsdam ME, et al. Prenatal diagnosis of congenital heart defects: accuracy and discrepancies in a multicenter cohort. Ultrasound Obstet Gynecol. May 2016;47(5):616–22. doi:10.1002/uog.15742

6. About Congenital Heart Disease. https://www.heart.org/en/health-topics/congenital-heart-defects/about-congenital-heart-defectsLinks to an external site.

7. Atrioventricular Canal (AVC) Defects. https://www.chop.edu/conditions-diseases/atrioventricular-canal-defectsLinks to an external site.

8. Ventricular Septal Defect (VSD). Ventricular Septal Defect (VSD)

9. Atrial Septal Defect. https://www.chop.edu/conditions-diseases/atrial-septal-defectLinks to an external site.

10. Tetralogy of Fallot (TOF). https://www.chop.edu/conditions-diseases/tetralogy-fallotLinks to an external site.

11. Bull MJ, Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics. Aug 2011;128(2):393–406. doi:10.1542/peds.2011-1605

12. Mahle WT, Martin GR, Beekman RH, 3rd, Morrow WR, Section on C, Cardiac Surgery Executive C. Endorsement of Health and Human Services recommendation for pulse oximetry screening for critical congenital heart disease. Pediatrics. Jan 2012;129(1):190–2. doi:10.1542/peds.2011-3211

13. Abbag FI. Congenital heart diseases and other major anomalies in patients with Down syndrome. Saudi Med J. Feb 2006;27(2):219–22. 

14. McGuire W FP. Routine screening by echocardiography to reduce morbidity and mortality from congenital heart disease in neonates with Down syndrome. Cochrane Database Syst Rev. 2009;doi:10.1002/14651858.CD005388

15. Gatzoulis MA, Beghetti M, Landzberg MJ, Galie N. Pulmonary arterial hypertension associated with congenital heart disease: recent advances and future directions. Int J Cardiol. Dec 15 2014;177(2):340–7. doi:10.1016/j.ijcard.2014.09.024

16. Fudge JC, Jr., Li S, Jaggers J, et al. Congenital heart surgery outcomes in Down syndrome: analysis of a national clinical database. Pediatrics. Aug 2010;126(2):315–22. doi:10.1542/peds.2009-3245

17. St Louis JD, Jodhka U, Jacobs JP, et al. Contemporary outcomes of complete atrioventricular septal defect repair: analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. J Thorac Cardiovasc Surg. Dec 2014;148(6):2526–31. doi:10.1016/j.jtcvs.2014.05.095

18. Schill EM, Wright CM, Jamil A, LaCombe JM, Roper RJ, Heuckeroth RO. Down syndrome mouse models have an abnormal enteric nervous system. JCI Insight. Apr 18 2019;5(11)doi:10.1172/jci.insight.124510

19. Li JC, Busch L, Kuhnel W. Immunohistochemical study on gastroenteric nervous system in trisomy 16 mice:an animal model of Down syndrome. World J Gastroenterol. Dec 2000;6(6):793–799. 

20. Li JC, Mi KH, Zhou JL, Busch L, Kuhnel W. The development of colon innervation in trisomy 16 mice and Hirschsprung's disease. World J Gastroenterol. Feb 2001;7(1):16–21. doi:10.3748/wjg.v7.i1.16

21. Moore SW. Advances in understanding the association between Down syndrome and Hirschsprung disease (DS-HSCR). Pediatr Surg Int. Nov 2018;34(11):1127–1137. doi:10.1007/s00383-018-4344-z

22. Heuckeroth RO. Hirschsprung's disease, Down syndrome, and missing heritability: too much collagen slows migration. J Clin Invest. Dec 2015;125(12):4323–6. doi:10.1172/JCI85003

23. Patel A, Yamashita N, Ascano M, et al. RCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome. Nat Commun. Dec 14 2015;6:10119. doi:10.1038/ncomms10119

24. Ciciora SL, Manickam K, Saps M. Disorders of Gut-Brain Interaction in a National Cohort of Children With Down Syndrome. J Neurogastroenterol Motil. Jan 30 2023;29(1):94–101. doi:10.5056/jnm22055

25. Bermudez B, de Oliveira CM, de Lima Cat MN, Magdalena NIR, Celli A. Gastrointestinal disorders in Down syndrome. Am J Med Genet A. Aug 2019;179(8):1426–1431. doi:10.1002/ajmg.a.61258

26. Rajindrajith S, Devanarayana NM, Crispus Perera BJ, Benninga MA. Childhood constipation as an emerging public health problem. World J Gastroenterol. Aug 14 2016;22(30):6864–75. doi:10.3748/wjg.v22.i30.6864

27. Schneider S, Wright CM, Heuckeroth RO. Unexpected Roles for the Second Brain: Enteric Nervous System as Master Regulator of Bowel Function. Annu Rev Physiol. Feb 10 2019;81:235–259. doi:10.1146/annurev-physiol-021317-121515

28. Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol. Mar 6 2012;9(5):286–94. doi:10.1038/nrgastro.2012.32

29. Heuckeroth RO. Hirschsprung disease - integrating basic science and clinical medicine to improve outcomes. Nat Rev Gastroenterol Hepatol. Mar 2018;15(3):152–167. doi:10.1038/nrgastro.2017.149

30. Elgendy MM, Cortez J, Saker F, Mohamed MA, Aly H. Prevalence and Outcomes of Gastrointestinal Anomalies in Down Syndrome. Am J Perinatol. Nov 2024;41(15):2047–2052. doi:10.1055/s-0044-1786874

31. Halleran DR, Ahmad H, Maloof E, et al. Does Hirschsprung-Associated Enterocolitis Differ in Children With and Without Down Syndrome? J Surg Res. Jan 2020;245:564–568. doi:10.1016/j.jss.2019.06.086

32. Soret R, Mennetrey M, Bergeron KF, et al. A collagen VI-dependent pathogenic mechanism for Hirschsprung's disease. J Clin Invest. Dec 2015;125(12):4483–96. doi:10.1172/JCI83178

33. Kuil LE, Chauhan RK, de Graaf BM, et al. ATP5PO levels regulate enteric nervous system development in zebrafish, linking Hirschsprung disease to Down Syndrome. Biochim Biophys Acta Mol Basis Dis. Mar 2024;1870(3):166991. doi:10.1016/j.bbadis.2023.166991

34. Bull MJ, Trotter T, Santoro SL, et al. Health Supervision for Children and Adolescents With Down Syndrome. Pediatrics. May 1 2022;149(5)doi:10.1542/peds.2022-057010

35. Maris M, Verhulst S, Wojciechowski M, Van de Heyning P, Boudewyns A. Prevalence of Obstructive Sleep Apnea in Children with Down Syndrome. Sleep. Mar 1 2016;39(3):699–704. doi:10.5665/sleep.5554

36. Uong EC, McDonough JM, Tayag-Kier CE, et al. Magnetic resonance imaging of the upper airway in children with Down syndrome. Am J Respir Crit Care Med. Mar 2001;163(3 Pt 1):731–6. doi:10.1164/ajrccm.163.3.2004231

37. Curry TA, Cooper E, Brinton J, et al. Co-Occurring Conditions and Sleep Symptoms Associated With Obstructive Sleep Apnea in Children With Down Syndrome. Pediatr Pulmonol. Nov 2025;60(11):e71376. doi:10.1002/ppul.71376

38. Seither K, Helm BM, Heubi C, Swarr D, Suhrie KR. Sleep Apnea in Children With Down Syndrome. Pediatrics. Mar 1 2023;151(3)doi:10.1542/peds.2022-058771

39. Hill CM, Evans HJ, Elphick H, et al. Prevalence and predictors of obstructive sleep apnoea in young children with Down syndrome. Sleep Med. Nov–Dec 2016;27-28:99–106. doi:10.1016/j.sleep.2016.10.001

40. Hizal M, Satirer O, Polat SE, et al. Obstructive sleep apnea in children with Down syndrome: is it possible to predict severe apnea? Eur J Pediatr. Feb 2022;181(2):735–743. doi:10.1007/s00431-021-04267-w

41. Bush D, Galambos C, Ivy DD, Abman SH, Wolter-Warmerdam K, Hickey F. Clinical Characteristics and Risk Factors for Developing Pulmonary Hypertension in Children with Down Syndrome. J Pediatr. Nov 2018;202:212–219 e2. doi:10.1016/j.jpeds.2018.06.031

42. Maloney MA, Ward SLD, Su JA, et al. Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea. J Clin Sleep Med. Jun 1 2022;18(6):1629–1637. doi:10.5664/jcsm.9944

43. Horne RS, Wijayaratne P, Nixon GM, Walter LM. Sleep and sleep disordered breathing in children with down syndrome: Effects on behaviour, neurocognition and the cardiovascular system. Sleep Med Rev. Apr 2019;44:1–11. doi:10.1016/j.smrv.2018.11.002

44. Capute AJ, & Accardo, P. J. Developmental disabilities in infancy and childhood. 1991.

45. Shelov SP, & Altmann, T. R. Caring for Your Baby and Young Child, Birth to Age 5. American Academy of Pediatrics; 2009.

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47. Nightengale E, Yoon P, Wolter-Warmerdam K, Daniels D, Hickey F. Understanding Hearing and Hearing Loss in Children With Down Syndrome. Am J Audiol. Sep 18 2017;26(3):301–308. doi:10.1044/2017_AJA-17-0010

48. Barr E, Dungworth J, Hunter K, McFarlane M, Kubba H. The prevalence of ear, nose and throat disorders in preschool children with Down's syndrome in Glasgow. Scott Med J. May 2011;56(2):98–103. doi:10.1258/smj.2011.011036

49. Yoshinaga-Itano C, Sedey AL, Coulter DK, Mehl AL. Language of early- and later-identified children with hearing loss. Pediatrics. Nov 1998;102(5):1161–71. doi:10.1542/peds.102.5.1161

50. Kreicher KL, Weir FW, Nguyen SA, Meyer TA. Characteristics and Progression of Hearing Loss in Children with Down Syndrome. J Pediatr. Feb 2018;193:27–33 e2. doi:10.1016/j.jpeds.2017.09.053

51. Tedeschi AS, Roizen NJ, Taylor HG, Murray G, Curtis CA, Parikh AS. The prevalence of congenital hearing loss in neonates with Down syndrome. J Pediatr. Jan 2015;166(1):168–71. doi:10.1016/j.jpeds.2014.09.005

52. Lieu JEC, Kenna M, Anne S, Davidson L. Hearing Loss in Children: A Review. JAMA. Dec 1 2020;324(21):2195–2205. doi:10.1001/jama.2020.17647

Module 3

1. Antonarakis SE, Skotko BG, Rafii MS, et al. Down syndrome. Nat Rev Dis Primers. 2020;6(1):9. Published 2020 Feb 6. doi:10.1038/s41572-019-0143-7

2. Illouz T, Biragyn A, Iulita MF, et al. Immune Dysregulation and the Increased Risk of Complications and Mortality Following Respiratory Tract Infections in Adults With Down Syndrome. Front Immunol. 2021;12:621440. Published 2021 Jun 25. doi:10.3389/fimmu.2021.621440

3. Malle L, Patel RS, Martin-Fernandez M, et al. Autoimmunity in Down's syndrome via cytokines, CD4 T cells and CD11c+ B cells. Nature. 2023;615(7951):305-314. doi:10.1038/s41586-023-05736-y

4. Waugh KA, Araya P, Pandey A, et al. Mass Cytometry Reveals Global Immune Remodeling with Multi-lineage Hypersensitivity to Type I Interferon in Down Syndrome. Cell Rep. 2019;29(7):1893-1908.e4. doi:10.1016/j.celrep.2019.10.038

5. Nakashima K, Imai T, Shiraishi A, et al. The immunoreactive signature of monocyte-derived dendritic cells from patients with Down syndrome. Clin Exp Immunol. 2024;217(3):291-299. doi:10.1093/cei/uxae048

6. Huggard D, McGrane F, Lagan N, et al. Altered endotoxin responsiveness in healthy children with Down syndrome. BMC Immunol. 2018;19(1):31. Published 2018 Nov 3. doi:10.1186/s12865-018-0270-z

7. Lambert K, Moo KG, Arnett A, et al. Deep immune phenotyping reveals similarities between aging, Down syndrome, and autoimmunity. Sci Transl Med. 2022;14(627):eabi4888. doi:10.1126/scitranslmed.abi4888

8. Sullivan KD, Lewis HC, Hill AA, et al. Trisomy 21 consistently activates the interferon response. Elife. 2016;5:e16220. Published 2016 Jul 29. doi:10.7554/eLife.16220

9. Araya P, Waugh KA, Sullivan KD, et al. Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity. Proc Natl Acad Sci U S A. 2019;116(48):24231-24241. doi:10.1073/pnas.1908129116

10. Valentini D, Marcellini V, Bianchi S, et al. Generation of switched memory B cells in response to vaccination in Down syndrome children and their siblings. Vaccine. 2015;33(48):6689-6696. doi:10.1016/j.vaccine.2015.10.083

11. Ramba M, Bogunovic D. The immune system in Down Syndrome: Autoimmunity and severe infections. Immunol Rev. 2024;322(1):300-310. doi:10.1111/imr.13296

12. Sullivan KD, Evans D, Pandey A, et al. Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation. Sci Rep. 2017;7(1):14818. Published 2017 Nov 1. doi:10.1038/s41598-017-13858-3

13. Pilkington SM, Bulfone-Paus S, Griffiths CEM, Watson REB. Inflammaging and the Skin. J Invest Dermatol. 2021;141(4S):1087-1095. doi:10.1016/j.jid.2020.11.006

14. Choy EH, De Benedetti F, Takeuchi T, Hashizume M, John MR, Kishimoto T. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol. 2020;16(6):335-345. doi:10.1038/s41584-020-0419-z

15. Morris EC, Neelapu SS, Giavridis T, Sadelain M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol. 2022;22(2):85-96. doi:10.1038/s41577-021-00547-6

16. Wang MJ, Zhang HL, Chen F, Guo XJ, Liu QG, Hou J. The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases. Exp Hematol Oncol. 2024;13(1):62. Published 2024 Jun 18. doi:10.1186/s40164-024-00527-1

17. Stine L, Cahill S, Humphries F. Interferons in human inborn errors of disease. mBio. 2025;16(8):e0157025. doi:10.1128/mbio.01570-25

18. Rachubinski AL, Wallace E, Gurnee E, et al. JAK inhibition decreases the autoimmune burden in Down syndrome. Elife. 2024;13:RP99323. Published 2024 Dec 31. doi:10.7554/eLife.99323

19. Krueger JG, Frew J, Jemec GBE, et al. Hidradenitis suppurativa: new insights into disease mechanisms and an evolving treatment landscape. Br J Dermatol. 2024;190(2):149-162. doi:10.1093/bjd/ljad345

20. Molinelli E, Gioacchini H, De Simoni E, et al. Hidradenitis suppurativa in chromosomal abnormalities, genodermatoses, and genetic disorders: a review. Clin Exp Dermatol. Published online November 13, 2025. doi:10.1093/ced/llaf506

21. van Straalen KR, Prens EP, Gudjonsson JE. Insights into hidradenitis suppurativa. J Allergy Clin Immunol. 2022;149(4):1150-1161. doi:10.1016/j.jaci.2022.02.003

22. Lepe K, Syed HA, Zito PM. Alopecia areata. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Updated October 30, 2023. Accessed March 10, 2026. https://www.ncbi.nlm.nih.gov/books/NBK537000/Links to an external site. 

23. Zhou C, Li X, Wang C, Zhang J. Alopecia Areata: an Update on Etiopathogenesis, Diagnosis, and Management. Clin Rev Allergy Immunol. 2021;61(3):403-423. doi:10.1007/s12016-021-08883-0

24. Rajabi F, Drake LA, Senna MM, Rezaei N. Alopecia areata: a review of disease pathogenesis. Br J Dermatol. 2018;179(5):1033-1048. doi:10.1111/bjd.16808

25. Sun Y, Li Q, Zhang Y, Liu Y. Janus kinase inhibitors for alopecia areata: a review of clinical data. Front Immunol. 2025;16:1577115. Published 2025 May 13. doi:10.3389/fimmu.2025.1577115

26. Jaguan D, Nguyen KT, Goldfarb N. Selective small molecule inhibitors for hidradenitis suppurativa: Today and tomorrow. J Am Acad Dermatol. 2024;91(6S):S31-S36. doi:10.1016/j.jaad.2024.09.014

27. Rachubinski AL, Estrada BE, Norris D, Dunnick CA, Boldrick JC, Espinosa JM. Janus kinase inhibition in Down syndrome: 2 cases of therapeutic benefit for alopecia areata. JAAD Case Rep. 2019;5(4):365-367. Published 2019 Apr 5. doi:10.1016/j.jdcr.2019.02.007

28. Bull MJ, Trotter T, Santoro SL, et al. Health Supervision for Children and Adolescents With Down Syndrome. Pediatrics. 2022;149(5):e2022057010. doi:10.1542/peds.2022-057010

29. Taylor PN, Medici MM, Hubalewska-Dydejczyk A, Boelaert K. Hypothyroidism. Lancet. 2024;404(10460):1347-1364. doi:10.1016/S0140-6736(24)01614-3

30. Szeliga K, Antosz A, Skrzynska K, Kalina-Faska B, Januszek-Trzciakowska A, Gawlik A. Subclinical Hypothyroidism as the Most Common Thyroid Dysfunction Status in Children With Down's Syndrome. Front Endocrinol (Lausanne). 2022;12:782865. Published 2022 Jan 4. doi:10.3389/fendo.2021.782865

31. Szybiak-Skora W, Cyna W, Lacka K. Autoimmune Thyroid Disease in Patients with Down Syndrome-Review. Int J Mol Sci. 2024;26(1):29. Published 2024 Dec 24. doi:10.3390/ijms26010029

32. American Thyroid Association. Hyperthyroidism. American Thyroid Association. Accessed March 6, 2026. https://www.thyroid.org/hyperthyroidism/Links to an external site.

33. Giménez-Barcons M, Casteràs A, Armengol Mdel P, et al. Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens. J Immunol. 2014;193(8):3872-3879. doi:10.4049/jimmunol.1400223

34. Nakhleh A, Robenshtok E, Adler L, et al. Clinical Characteristics and Outcomes of Graves' Disease in Individuals with Prior Hypothyroidism. J Clin Endocrinol Metab. 2026;111(2):348-357. doi:10.1210/clinem/dgaf426

35. Cattoni A, Molinari S, Capitoli G, et al. Thyroid Function Tests in Children and Adolescents With Trisomy 21: Definition of Syndrome-Specific Reference Ranges. J Clin Endocrinol Metab. 2023;108(11):2779-2788. doi:10.1210/clinem/dgad333

36. Stoupa A, Kariyawasam D, Muzza M, et al. New genetics in congenital hypothyroidism. Endocrine. 2021;71(3):696-705. doi:10.1007/s12020-021-02646-9

37. Khatri A, Dutta S, Mukhopadhyay A, et al. DYRK1A Expression and Thyroid Dysfunction in Subjects With Down Syndrome. Clin Endocrinol (Oxf). Published online January 29, 2026. doi:10.1111/cen.70099

38. Agency for Healthcare Research and Quality. Diagnosis of celiac disease. Comparative Effectiveness Review No. 162. Rockville, MD: Agency for Healthcare Research and Quality; January 2016. Accessed March 6, 2026. https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/celiac-disease_research.pdfLinks to an external site.

39. Swigonski NL, Kuhlenschmidt HL, Bull MJ, Corkins MR, Downs SM. Screening for celiac disease in asymptomatic children with Down syndrome: cost-effectiveness of preventing lymphoma. Pediatrics. 2006;118(2):594-602. doi:10.1542/peds.2005-2123

40. Aslam AA, Baksh RA, Pape SE, et al. Diabetes and Obesity in Down Syndrome Across the Lifespan: A Retrospective Cohort Study Using U.K. Electronic Health Records. Diabetes Care. Published online September 30, 2022. doi:10.2337/dc22-0482

41. American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):S27-S49. doi:10.2337/dc25-S002

42. Mathieu C, Sims EK, Chatenoud L, James EA, Atkinson MA, Herold KC. Toward Disease-Modifying Therapies in Type 1 Diabetes: Focus on Teplizumab. Diabetes Care. 2026;49(3):365-374. doi:10.2337/dci25-0066

43. Mortimer GL, Gillespie KM. Early Onset of Autoimmune Diabetes in Children with Down Syndrome-Two Separate Aetiologies or an Immune System Pre-Programmed for Autoimmunity?. Curr Diab Rep. 2020;20(9):47. Published 2020 Aug 25. doi:10.1007/s11892-020-01318-8

44. Zemel BS, Pipan M, Stallings VA, et al. Growth Charts for Children With Down Syndrome in the United States. Pediatrics. 2015;136(5):e1204-e1211. doi:10.1542/peds.2015-1652

45. Cronk C, Crocker AC, Pueschel SM, et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediatrics. 1988;81(1):102-110.

46. Centers for Disease Control and Prevention. Growth charts for children with Down syndrome. Centers for Disease Control and Prevention. Updated November 19, 2024. Accessed March 6, 2026. https://www.cdc.gov/birth-defects/hcp/down-syndrome-growth-charts/index.htmlLinks to an external site.

47. Styles ME, Cole TJ, Dennis J, Preece MA. New cross-sectional stature, weight, and head circumference references for Down's syndrome in the UK and Republic of Ireland. Arch Dis Child. 2002;87(2):104-108. doi:10.1136/adc.87.2.104

48. Myrelid A, Gustafsson J, Ollars B, Annerén G. Growth charts for Down's syndrome from birth to 18 years of age. Arch Dis Child. 2002;87(2):97-103. doi:10.1136/adc.87.2.97

49. Van Gameren-Oosterom HB, Van Dommelen P, Oudesluys-Murphy AM, Buitendijk SE, Van Buuren S, Van Wouwe JP. Healthy growth in children with Down syndrome. PLoS One. 2012;7(2):e31079. doi:10.1371/journal.pone.0031079

50. Ogden CL, Freedman DS, Hales CM. CDC Extended BMI-for-Age Percentiles Versus Percent of the 95th Percentile. Pediatrics. 2023;152(3):e2023062285. doi:10.1542/peds.2023-062285

51. Centers for Disease Control and Prevention. Extended BMI-for-age growth charts. Centers for Disease Control and Prevention. Reviewed September 2, 2024. Accessed March 6, 2026. https://www.cdc.gov/growthcharts/Extended-BMI-Charts.htmlLinks to an external site.

52. Hatch-Stein JA, Zemel BS, Prasad D, et al. Body Composition and BMI Growth Charts in Children With Down Syndrome. Pediatrics. 2016;138(4):e20160541. doi:10.1542/peds.2016-0541

53. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC growth charts: United States. Adv Data. 2000;(314):1-27.

54. Poetsch MS, Strano A, Guan K. Role of Leptin in Cardiovascular Diseases. Front Endocrinol (Lausanne). 2020;11:354. Published 2020 Jun 16. doi:10.3389/fendo.2020.00354

55. Magge SN, O'Neill KL, Shults J, Stallings VA, Stettler N. Leptin levels among prepubertal children with Down syndrome compared with their siblings. J Pediatr. 2008;152(3):321-326. doi:10.1016/j.jpeds.2007.08.008

56. Adelekan T, Magge S, Shults J, Stallings V, Stettler N. Lipid profiles of children with Down syndrome compared with their siblings. Pediatrics. 2012;129(6):e1382-e1387. doi:10.1542/peds.2011-1262

57. Magge SN, Zemel BS, Pipan ME, Gidding SS, Kelly A. Cardiometabolic Risk and Body Composition in Youth With Down Syndrome. Pediatrics. 2019;144(2):e20190137. doi:10.1542/peds.2019-0137

58. Sordo L, Du A, Sandadi V, et al. Leptin levels are associated with body mass index and Alzheimer's disease in Down syndrome. Alzheimers Dement. 2025;21(7):e70448. doi:10.1002/alz.70448

Module 4

1. Arnell H, Gustafsson J, Ivarsson SA, Annerén G. Growth and pubertal development in Down syndrome. Acta Paediatr. 1996;85(9):1102-1106. doi:10.1111/j.1651-2227.1996.tb14225.x

2. Pueschel SM, Orson JM, Boylan JM, Pezzullo JC. Adolescent development in males with Down syndrome. Am J Dis Child. 1985;139(3):236-238. doi:10.1001/archpedi.1985.02140050030014

3. Arnell H, Gustafsson J, Ivarsson SA, Annerén G. Growth and pubertal development in Down syndrome. Acta Paediatr. 1996;85(9):1102-1106. doi:10.1111/j.1651-2227.1996.tb14225.x

4. Pueschel SM, Orson JM, Boylan JM, Pezzullo JC. Adolescent development in males with Down syndrome. Am J Dis Child. 1985;139(3):236-238. doi:10.1001/archpedi.1985.02140050030014

5. Magge SN, Zemel BS, Pipan ME, Gidding SS, Kelly A. Cardiometabolic Risk and Body Composition in Youth With Down Syndrome. Pediatrics. 2019;144(2):e20190137. doi:10.1542/peds.2019-0137

6. Goede J, Weijerman ME, Broers CJ, de Winter JP, van der Voort-Doedens LM, Hack WW. Testicular volume and testicular microlithiasis in boys with Down syndrome. J Urol. 2012;187(3):1012-1017. doi:10.1016/j.juro.2011.10.167

7. Hsiang YH, Berkovitz GD, Bland GL, Migeon CJ, Warren AC. Gonadal function in patients with Down syndrome. Am J Med Genet. 1987;27(2):449-458. doi:10.1002/ajmg.1320270223

8. Korkes F, Gomez-Bueno MP, García-Perdomo HA. Incidence of urological tumors in Down's syndrome: a systematic review and meta-analysis. Int Urol Nephrol. 2023;55(10):2381-2387. doi:10.1007/s11255-023-03656-4

9. Smith AJB, Applebaum J, Tanner EJ, Capone GT. Gynecologic Care in Women With Down Syndrome: Findings From a National Registry. Obstet Gynecol. 2020;136(3):518-523. doi:10.1097/AOG.0000000000003997

10. Bull MJ, Trotter T, Santoro SL, et al. Health Supervision for Children and Adolescents With Down Syndrome. Pediatrics. 2022;149(5):e2022057010. doi:10.1542/peds.2022-057010

11. Pikora TJ, Bourke J, Bathgate K, Foley KR, Lennox N, Leonard H. Health conditions and their impact among adolescents and young adults with Down syndrome. PLoS One. 2014;9(5):e96868. Published 2014 May 12. doi:10.1371/journal.pone.0096868

12. Wandresen G, Sgarbi F, Nisihara R. Management of contraceptives and menstrual complaints in patients with Down syndrome. Gynecol Endocrinol. 2019;35(2):103-108. doi:10.1080/09513590.2018.1501017

13. Gynecologic Management of Adolescents and Young Women With Seizure Disorders: ACOG Committee Opinion Summary, Number 806. Obstet Gynecol. 2020;135(5):1242-1243. doi:10.1097/AOG.0000000000003828

14. Goldberg-Stern H, Strawsburg RH, Patterson B, et al. Seizure frequency and characteristics in children with Down syndrome. Brain Dev. 2001;23(6):375-378. doi:10.1016/s0387-7604(01)00239-x

15. Horner-Johnson W, Klein KA, Campbell J, Guise JM. "It Would Have Been Nice to Have a Choice": Barriers to Contraceptive Decision-making among Women with Disabilities. Womens Health Issues. 2022;32(3):261-267. doi:10.1016/j.whi.2022.01.001

16. Roden RC, Schmidt EK, Holland-Hall C. Sexual health education for adolescents and young adults with intellectual and developmental disabilities: recommendations for accessible sexual and reproductive health information. Lancet Child Adolesc Health. 2020;4(9):699-708. doi:10.1016/S2352-4642(20)30098-5

17. Suzuki K, Nakajima K, Kamimura S, et al. Eight case reports on sex-hormone profiles in sexually mature male Down syndrome. Int J Urol. 2010;17(12):1008-1010. doi:10.1111/j.1442-2042.2010.02621.x

18. Seltzer GB, Schupf N, Wu HS. A prospective study of menopause in women with Down's syndrome. J Intellect Disabil Res. 2001;45(Pt 1):1-7. doi:10.1046/j.1365-2788.2001.00286.x

19. Schupf N, Pang D, Patel BN, et al. Onset of dementia is associated with age at menopause in women with Down's syndrome. Ann Neurol. 2003;54(4):433-438. doi:10.1002/ana.10677

20. Nishat F, Lunsky Y, Tarasoff LA, Brown HK. Prenatal Care Adequacy Among Women With Disabilities: A Population-Based Study. Am J Prev Med. 2022;62(1):39-49. doi:10.1016/j.amepre.2021.05.037

21. Access to Obstetric and Gynecologic Care for Patients With Disabilities: ACOG Committee Statement No. 18. Obstetrics & Gynecology e145(5):p 553-563, May 17, 2025. | DOI: 10.1097/AOG.0000000000005879

22. Graham Holmes L, Rast JE, Roux AM, Rothman EF. Reproductive Health and Substance Use Education for Autistic Youth. Pediatrics. 2022;149(Suppl 4):e2020049437T. doi:10.1542/peds.2020-049437T

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