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La fréquence de la trisomie 21 est de 1/700 naissances. La fréquence réelle est très supérieure mais 6 embryons ou fetus sur 7 porteurs de trisomie 21 meurent in utero (avortement spontané). La méiose pourrait donner à la suite d’une non-disjonction de venture inconnue, deux cellules germinales (ovocytes) : l’une avec 24 chromosomes (deux chromosomes 21 au lieu d’un) et l’une avec 22 chromosomes (aucun chromosome 21). Si l’ovule avec deux chromosomes 21 est fécondé par un spermatozoïde normal, on aboutit à un embryon porteur de trois chromosomes 21. Plus la plain est âgée, plus le risque de mauvaise distribution des chromosomes lors de la méiose est grand : 1/100 après 40 ans et 1/46 après 45 ans. Comme beaucoup asset de mères ont des enfants entre 20 et 25 ans qu’entre 40 et 45 ans, il n’est pas rarefied de rencontrer des enfants trisomiques de mères jeunes.

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