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Recurrent trisomy 21: four cases in three generations.
1Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Clinical Genetics
|October 7, 2005
Summary
This study reports four cases of Down syndrome (free trisomy 21) across three generations in one family, suggesting a potential inherited genetic factor. Researchers identified a possible cryptic rearrangement on chromosome 21, increasing non-disjunction risk.
Area of Science:
- Genetics
- Human Genetics
- Reproductive Genetics
Background:
- Recurrence of trisomy 21 (T21) is typically attributed to gonadal mosaicism in a single couple.
- The occurrence of free T21 in multiple, unrelated individuals within a single family pedigree is rare.
Observation:
- An unusual pedigree presented with four instances of Down syndrome (DS) due to free T21.
- Affected individuals were born to four different mothers across three generations of the same family.
- Mothers' ages at birth ranged from 18 to approximately 30 years.
Findings:
- Microsatellite analysis excluded most of chromosome 21, identifying shared regions 21q11.1 and 21q22.3 among mothers.
- Two family members, including a DS mother with a normal karyotype, possessed supernumerary alleles in the 21pter-21q11.1 region.
- FISH analysis ruled out cryptic centromeric translocations involving chromosome 21, except possibly with chromosome 13.
- An unusually high level of meiotic recombination on chromosome 21 was observed in this family.
Implications:
- A cryptic rearrangement in the 21q11.1 region is hypothesized to disrupt chromosome pairing.
- This disruption may lead to an elevated risk of chromosome 21 non-disjunction within the family.
- The findings highlight the potential for familial predisposition to trisomy 21 beyond gonadal mosaicism.