genetics

Last edited 06/2020

Approximately 95% of affected individuals have trisomy 21, with a chromosome count of 47. In Down's syndrome due to trisomy 21 there is about a 10 times increased risk of having a Down's child in a subsequent pregnancy, ie increased from 1 in 600 to about 1 in 60.

In approximately 3-5% percent of babies with Down's syndrome a translocation or mosaicism is the cause of the condition. Examination of the parental chromosomes is only necessary if a translocation is found in the baby. The risk of a subsequent child having Down's syndrome is substantially increased if either parent has a translocation.

Chromosomal Basis of Down Syndrome

Chromosomal Feature Description Approximate Percent of Cases
Meiotic nondisjunction

Occurs in the egg in 95% of cases

  • the risk increases with mother’s age
 95
Translocation

Usually occurs with one chromosome 21 attached to chromosome 14, 21, or 22

In 14/21 translocation

  • 1 of every 3 cases involves a parental carrier
  • in 90% of such cases, the carrier is the mother
  • risk of recurrence is 10–15% with a maternal carrier and 2–5% with a paternal carrier

In 21/21 translocation

  • 1 of every 14 cases involves a parental carrier
  • in 50% of such cases, the carrier is the father
 3-4
Mosaicism

The number of affected cells varies among persons

  • clinical findings vary widely - there are fewer medical complications and often less severe intellectual disability in cases characterized by mosaicism
 1-2
Partial trisomy Duplication of a delimited segment of chromosome 21 is present <1

Reference:

  • Bull MJ. Down Syndrome.N Engl J Med 2020;382:2344-52.