KEGG   DISEASE: Down syndromeHelp
Entry
H01552                      Disease                                

Name
Down syndrome;
Trisomy 21
Description
Down syndrome (DS), a genetic condition characterized by mental retardation and distinctive facial appearance, is caused by trisomy of chromosome 21 (HSA21). Down syndrome (DS) is the most common chromosomal malformation in newborns. Throughout the world, the overall prevalence of DS is 1 per 1,000 live births, although in recent years this figure has been increasing. Roughly 95% of cases of DS are due to the presence of an extra (third) copy of HSA21. Most often, the non-disjunction event leading to DS occurs in maternal meiosis I. In about 5% of patients, 1 copy is translocated to another acrocentric chromosome, most often chromosome 14 or 21. In 2 to 4% of cases with free trisomy 21 there is recognizable mosaicism for a trisomic and a normal cell line. DS occurs at a much higher incidence in older mothers. Nonetheless, the vast majority of DS births are to younger mothers. Clinical and experimental studies have shown that age independent DNA hypo-methylation is associated with chromosomal instability and abnormal segregation. Recent studies have linked the increased frequency of polymorphism of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase gene (MTRR) in mothers with DS child. The phenotypic features of DS are quite variable from person to person and include learning disability, heart defects, early-onset Alzheimer's disease and childhood leukaemia. This phenotypic variation is likely to be caused by a combination of environmental and genetic causes. Genetic polymorphisms in both Hsa21 and non-Hsa21 genes may account for much of this variation. Trisomy of Hsa21 has a significant impact on the development of many tissues, most notably the heart and the brain. A recent paper has suggested that RCAN1 and DYRK1A, localized in the Down syndrome critical region (DSCR) of HSA21, may have an impact on the development of multiple tissues.
Category
Chromosomal abnormality
Brite
Human diseases [BR:br08402]
 Other congenital disorders
  Chromosomal abnormalities
   H01552  Down syndrome
Human diseases in ICD-11 classification [BR:br08403]
 20 Developmental anomalies
  Chromosomal anomalies, excluding gene mutations
   LD40  Complete trisomies of the autosomes
    H01552  Down syndrome
BRITE hierarchy
Gene
RCAN1 [HSA:1827] [KO:K17901]
DYRK1A [HSA:1859] [KO:K08825]
MTHFR (maternal polymorphism) [HSA:4524] [KO:K00297]
MTRR (maternal polymorphism) [HSA:4552] [KO:K00597]
Other DBs
ICD-11: LD40.0
ICD-10: Q90
MeSH: D004314
OMIM: 190685
Reference
  Authors
Wiseman FK, Alford KA, Tybulewicz VL, Fisher EM
  Title
Down syndrome--recent progress and future prospects.
  Journal
Hum Mol Genet 18:R75-83 (2009)
DOI:10.1093/hmg/ddp010
Reference
  Authors
Sommer C, Henrique-Silva F
  Title
Trisomy 21 and Down syndrome: a short review.
  Journal
Braz J Biol 68:447-52 (2008)
DOI:10.1590/S1519-69842008000200031
Reference
PMID:26062604 (gene, marker)
  Authors
Asim A, Kumar A, Muthuswamy S, Jain S, Agarwal S
  Title
"Down syndrome: an insight of the disease".
  Journal
J Biomed Sci 22:41 (2015)
DOI:10.1186/s12929-015-0138-y
Reference
  Authors
Birger Y, Izraeli S
  Title
DYRK1A in Down syndrome: an oncogene or tumor suppressor?
  Journal
J Clin Invest 122:807-10 (2012)
DOI:10.1172/JCI62372
Reference
PMID:12626825 (maternal polymorphism)
  Authors
Sheth JJ, Sheth FJ
  Title
Gene polymorphism and folate metabolism: a maternal risk factor for Down syndrome.
  Journal
Indian Pediatr 40:115-23 (2003)
Reference
PMID:16390612 (marker)
  Authors
Harrison G, Goldie D
  Title
Second-trimester Down's syndrome serum screening: double, triple or quadruple marker testing?
  Journal
Ann Clin Biochem 43:67-72 (2006)
DOI:10.1258/000456306775141876
Reference
PMID:25598039 (marker)
  Authors
Zhang H, Gao Y, Jiang F, Fu M, Yuan Y, Guo Y, Zhu Z, Lin M, Liu Q, Tian Z, Zhang H, Chen F, Lau TK, Zhao L, Yi X, Yin Y, Wang W
  Title
Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146,958 pregnancies.
  Journal
Ultrasound Obstet Gynecol 45:530-8 (2015)
DOI:10.1002/uog.14792

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