Down syndrome - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Down syndrome is the most common genetic cause of cognitive or intellectual disability, with a prevalence of 1 in 800 births wordwide.
Characteristic physical features include brachycephaly with a flat occiput; epicanthal folds and upslanting palpebral fissures; Brushfield spots in the iris; low nasal bridge; low-set ears; broad neck; and small hands with transverse crease.
Individuals with Down syndrome have a higher frequency of congenital and acquired medical conditions, including congenital heart defects and audiologic, vision, gastrointestinal, hematologic, and thyroid issues.
Global developmental delay is common; however, cognitive abilities vary greatly, with IQ ranging from mild to moderate intellectual disability. Behavioral difficulties, if present, tend to be age-related (e.g., hyperactivity and impulsiveness in younger children; withdrawal and anxiety in older adolescents).
Early interventional therapies (e.g., speech therapy, physical therapy, occupational therapy) and individualized educational programs/resources are essential to maximize the potential of a person with Down syndrome.

A 5-year-old boy with Down syndrome

From the personal collection of Dr Jeannie Visootsak; photo used with parental consent

Quick Reference

History & Exam
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Definition

Epidemiology

Etiology

Pathophysiology

Images

Girl with Down syndrome
Boy with mosaic Down syndrome, diagnosed at 18 months
A 5-year-old boy with Down syndrome

Citations

Key Articles

Bull MJ, Trotter T, Santoro SL, et al. Council on Genetics, American Academy of Pediatrics. Health supervision for children and adolescents with Down syndrome. Pediatrics. 2022;149 (5): e2022057010.[Full Text]

Referenced Articles

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4. Hunter AGW. Down syndrome. In: Cassidy SB, Allanson JE, eds. Management of genetic syndromes, 2nd ed. Hoboken, NJ: Wiley-Liss; 2005:191-210.
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10. Freeman SB, Allen EG, Oxford-Wright CL, et al. The National Down Syndrome Project: design and implementation. Public Health Rep. 2007;122:62-72.[Abstract][Full Text]
11. Nussbaum R, McInnes R, Willard H, et al. Thompson & Thompson genetics in medicine, 6th ed. Philadelphia, PA: Saunders; 2004:157-79.
12. Reeves RH, Garner CC. A year of unprecedented progress in Down syndrome basic research. Ment Retard Dev Disabil Res Rev. 2007;13:215-20.[Abstract]
13. Salehi A, Faizi M, Belichenko PV, et al. Using mouse models to explore genotype-phenotype relationship in Down syndrome. Ment Retard Dev Disabil Res Rev. 2007;13:207-14.[Abstract]
14. Sherman SL, Freeman SB, Allen EG, et al. Risk factors for nondisjunction of trisomy 21. Cytogenet Genome Res. 2005;111:273-80.[Abstract]
15. Hook EB, Fabia JJ. Frequency of Down syndrome in livebirths by single-year maternal age interval: results of a Massachusetts study. Teratology. 1978;17:223-8.[Abstract]
16. Bull MJ, Trotter T, Santoro SL, et al. Council on Genetics, American Academy of Pediatrics. Health supervision for children and adolescents with Down syndrome. Pediatrics. 2022;149 (5): e2022057010.[Full Text]
17. Jones KL. Smith's recognizable patterns of human malformation, 6th ed. Philadelphia, PA: Elsevier Saunders; 2006:7-11.
18. Skotko B. Mothers of children with Down syndrome reflect on their postnatal support. Pediatrics. 2005;115:64-77.[Abstract]
19. Skotko BG, Capone GT, Kishnani PS; Down Syndrome Diagnosis Study Group. Postnatal diagnosis of Down syndrome: synthesis of the evidence on how best to deliver the news. Pediatrics. 2009;124:e751-8.[Abstract]
20. Skotko BG. Prenatally diagnosed Down syndrome: mothers who continued their pregnancies evaluate their health care providers. Am J Obstet Gynecol. 2005;192:670-7.[Abstract]
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26. Van Cleve SN, Cohen WI. Part I: clinical practice guidelines for children with Down syndrome from birth to 12 years. J Pediatr Health Care. 2006;20:47-54.[Abstract]
27. Bermudez BEBV, de Oliveira CM, de Lima Cat MN, et al. Gastrointestinal disorders in Down syndrome. Am J Med Genet A. 2019 Aug;179(8):1426-31.[Abstract]
28. Loffredo CA, Hirata J, Wilson PD, et al. Atrioventricular septal defects: possible etiologic differences between complete and partial defects. Teratology. 2001;63:87-93.[Abstract]
29. Shott SR, Joseph A, Heithaus D. Hearing loss in children with Down syndrome. Int J Pediatr Otorhinolaryngol. 2001;61:199-205.[Abstract]
30. Van Cleve SN, Cannon S, Cohen WI. Part II: clinical practice guidelines for adolescents and young adults with Down syndrome: 12 to 21 years. J Pediatr Health Care. 2006;20:198-205.[Abstract]
31. American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 77: screening for fetal chromosomal abnormalities. Oct 2020 [internet publication].[Full Text]
32. Wapner R, Thom E, Simpson JL, et al. First-trimester screening for trisomies 21 and 18. N Engl J Med. 2003;349:1405-13.[Abstract][Full Text]
33. Spencer K, Spencer CE, Power M, et al. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience. BJOG. 2003;110:281-6.[Abstract][Full Text]
34. Alldred SK, Takwoingi Y, Guo B, et al. First trimester serum tests for Down's syndrome screening. Cochrane Database Syst Rev. 2015;(11):CD011975.[Abstract][Full Text]
35. Alldred SK, Takwoingi Y, Guo B, et al. First trimester ultrasound tests alone or in combination with first trimester serum tests for Down's syndrome screening. Cochrane Database Syst Rev. 2017 Mar 15;3(3):CD012600.[Abstract][Full Text]
36. Alldred SK, Takwoingi Y, Guo B, et al. First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening. Cochrane Database Syst Rev. 2017 Mar 15;3(3):CD012599.[Abstract][Full Text]
37. Smith M, Visootsak J. Noninvasive screening tools for Down syndrome: a review. Int J Womens Health. 2013;5:125-31.[Abstract][Full Text]
38. Porreco RP, Garite TJ, Maurel K, et al. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Am J Obstet Gynecol. 2014;211:365.[Abstract][Full Text]
39. Badeau M, Lindsay C, Blais J, et al. Genomics-based non-invasive prenatal testing for detection of fetal chromosomalaneuploidy in pregnant women. Cochrane Database Syst Rev. 2017 Nov 10;11:CD011767. [Abstract][Full Text]
40. American College of Obstetricians and Gynecologists. Committee opinion no. 640: cell-free DNA screening for fetal aneuploidy. Obstet Gynecol. 2015;126:e31-7.[Abstract]
41. Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005;353:2001-11.[Abstract][Full Text]
42. Smith-Bindman R, Hosmer W, Feldstein VA, et al. Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis. JAMA. 2001;285:1044-55.[Abstract]
43. Gregg AR, Skotko BG, Benkendorf JL, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016 Oct;18(10):1056-65.[Abstract][Full Text]
44. Winders PC. Gross motor skills in children with Down syndrome: a guide for parents and professionals. Bethesda, MD: Woodbine House; 1997:1-4.
45. Kumin L. Speech and language skills in children with Down syndrome. Ment Retard Dev Disabil. 1996;2:109-15.
46. Lemons CJ, Fuchs D. Phonological awareness of children with Down syndrome: its role in learning to read and the effectiveness of related interventions. Res Dev Disabil. 2010;31:316-30.[Abstract]
47. Wehman P, Hill M, Hill JW, et al. Competitive employment for persons with mental retardation: a follow-up six years later. Ment Retard. 1985;23:274-81.[Abstract]
48. Salman M. Systematic review of the effect of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome. Eur J Paediatr Neurol. 2002;6:213-9.[Abstract]
49. Livingstone N, Hanratty J, McShane R, et al. Pharmacological interventions for cognitive decline in people with Down syndrome. Cochrane Database Syst Rev. 2015;(10):CD011546.[Abstract][Full Text]
50. American College of Medical Genetics. Statement on nutritional supplements and piracetam for children with Down syndrome. 1996. http://www.acmg.net (last accessed 24 Jul 2017).[Full Text]
51. National Down Syndrome Society. Vitamin therapy position statement. http://www.ndss.org (last accessed 24 Jul 2017).[Full Text]
52. Fernandez F, Morishita W, Zuniga E, et al. Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat Neurosci. 2007;10:411-3.[Abstract]
53. Wiseman FK. Cognitive enhancement therapy for a model of Down syndrome. Sci Transl Med. 2009;18;1:7ps9. [Abstract]
54. Tsou AY, Bulova P, Capone G, et al; Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup. Medical care of adults with Down syndrome: a clinical guideline. JAMA. 2020 Oct 20;324(15):1543-56.[Abstract]
55. Tunstall O, Bhatnagar N, James B, et al; British Society for Haematology. Guidelines for the investigation and management of Transient Leukaemia of Down Syndrome. Br J Haematol. 2018 Jul;182(2):200-11.[Abstract][Full Text]
56. Baird PA, Sadovnick AD. Life expectancy in Down syndrome adults. Lancet. 1988;2:1354-6.[Abstract]
57. Yang Q, Rasmussen SA, Friedman JM. Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet. 2002;359:1019-25.[Abstract]
58. Rasmussen SA, Wong LY, Correa A, et al. Survival in infants with Down syndrome, Metropolitan Atlanta, 1979-1998. J Pediatr. 2006;148:806-12.[Abstract]
59. Bittles AH, Bower C, Hussain R, et al. The four ages of Down syndrome. Eur J Public Health. 2007;17:221-5.[Abstract]
60. Glasson EJ, Jacques A, Wong K, et al. Improved survival in Down syndrome over the last 60 years and the impact of perinatal factors in recent decades. J Pediatr. 2016;169:214-20.[Abstract][Full Text]
61. Wang Y, Liu G, Canfield MA, et al. Racial/ethnic differences in survival of United States children with birth defects: a population-based study. J Pediatr. 2015;166:819-26.[Abstract][Full Text]
62. Shott SR. Down syndrome: common otolaryngologic manifestations. Am J Med Genet C Semin Med Genet. 2006;142C:131-40.[Abstract]
63. Shott SR, Amin R, Chini B, et al. Obstructive sleep apnea: should all children with Down syndrome be tested? Arch Otolaryngol Head Neck Surg. 2006;132:432-6.[Abstract][Full Text]
64. Trois MS, Capone GT, Lutz JA, et al. Obstructive sleep apnea in adults with Down syndrome. J Clin Sleep Med. 2009;5:317-23.[Abstract][Full Text]
65. Zigman WB, Lott IT. Alzheimer's disease in Down syndrome: neurobiology and risk. Ment Retard Dev Disabil Res Rev. 2007;13:237-46.[Abstract]
66. Cronk C, Crocker AC, Pueschel SM, et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediatrics. 1988;81:102-10.[Abstract]
67. DiGuiseppi C, Hepburn S, Davis JM, et al. Screening for autism spectrum disorders in children with Down syndrome: population prevalence and screening test characteristics. J Dev Behav Pediatr. 2010;31:181-91.[Abstract]
68. Capone G, Goyal P, Ares W, et al. Neurobehavioral disorders in children, adolescents, and young adults with Down syndrome. Am J Med Genet C Semin Med Genet. 2006;142C:158-72.[Abstract]
69. Hitzler JK, Zipursky A. Origins of leukaemia in children with Down syndrome. Nat Rev Cancer. 2005;5:11-20.[Abstract]
70. Goldberg-Stern H, Strawsburg RH, Patterson B, et al. Seizure frequency and characteristics in children with Down syndrome. Brain Dev. 2001;23:375-8.[Abstract]
71. Hasle H, Friedman JM, Olsen JH, et al. Low risk of solid tumors in persons with Down syndrome. Genet Med. 2016 Nov;18(11):1151-57.[Abstract][Full Text]
72. Zemel BS, Pipan M, Stallings VA, et al. Growth charts for children with Down Syndrome in the United States. Pediatrics. 2015;136:e1204-11.[Abstract][Full Text]