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last update : 18-11-2020
Symbol TRI21
Location 21q22-q22.13
Name trisomy 21
Other name(s) Down syndrome
Corresponding gene DYRK1A , RCAN1 , APP , KCNJ6 , SIM2
Other symbol(s) T21, DS
Main clinical features
  • flat facial profile with upslanting palpebral fissures, speckling of iris (Brushfield's spots), small nose, open mouth with protruding tongue, small ears, brachycephaly with flat occiput
  • short limbs and small hands with frequent single palmar crease and short 5th middle phalange, pelvis dysplasia with flaring of iliac wings
  • hyperflexibility of the joints, hypotonia and poor Moro reflex at birth
  • congenital heart disease in half of children (atrioventricular defect and others), hearing loss and ophtalmological problems should be assessed for
  • ~10% of infants present with transient myeloproliferative disorder (TMD) at or shortly after birth. TMD may be a precursor to AMKL.
  • early occurence of Alzheimer disease
  • prenatal screening and diagnostic are improving with combined use of maternal serum and fetal ultrasound testing
  • intrinsic disturbance of multilineage myeloid hematopoiesis in trisomy 21 at the fetal liver stage (PMID: 23045682)), and T21 itself causes multiple distinct defects in fetal liver myelo- and lymphopoiesis (PMID: 23045701))
  • Genetic determination chromosomal
    Prevalence about 1 in 800 live births
    Related entries TAM, AMKLDS
    Function/system disorder multisystem/generalized
    mental retardation
    Type MCA/MR
    Gene product
    Name contiguous gene syndrome with more than 400 known genes
    Gene mutationChromosome rearrangementEffectComments
      aneuploidy over-expression regular trisomy 21 with a 47,+21 karyotype in about 95 percent of patients, mosaicism in 1-2 percent of patients
      translocation over-expression unbalanced Robertsonian translocation in 3-4 percent of patients mainly 14;21 arising de novo or due to malsegregation of a familial translocation
      isochromosome over-expression 21;21 translocation or isochromosome almost all de novo
      translocation over-expression concommitant familial translocation and meiotic 3:1 disjunction
      other over-expression a variety of other, extremely rare rearrangements have been observed
  • gene-expression variation in DS suggests 3 groups of genes, with group A genes being the most dosage sensitive and the most likely involved in the constant DS traits
  • older mothers who have babies with Down syndrome are "genetically older" than controls, who have euploid babies at the same age and telomere length attrition may be associated in some way with meiosis I and meiosis II nondisjunction of chromosome 21 and subsequent Down syndrome births at advanced maternal age (Ghosh 2010)
  • trisomy 21 causes increased production of haemogenic endothelial cells, haematopoietic stem cell precursors and increased colony forming potential, with significantly increased immature progenitors, leading to increased leukaemia risk (PMID: 20697343))
  • Genotype/Phenotype correlations
  • DS phenotype is thought to result of dysregulation of critical chr21 genes and associated molecular pathways: NFAT transcription factors pathway and Sonic Hedgehog pathway, and DYRK1A-mediated deregulation of REST in 4q ; acquired somatic mutations in exon 2 of hematopoietic transcription factor GATA1 have been found in individuals with Down syndrome with both transient myeloproliferative disorder and acute megakaryoblastic leukemia ; allelic variation in a RET enhancer interacts with T21 increasing the risk for HSCR ;
  • trisomy for synaptojanin1 in Down syndrome is functionally linked to the enlargement of early endosomes (PMID: 22511594))
  • apigenin is a candidate prenatal treatment for TRI21 (apigenin is a safe treatment that can rescue oxidative stress and total antioxidant capacity imbalance in human amniocytes from fetuses with Tri21) (PMID: 33098770))