Family History of Down Syndrome and Trisomy Risk
A woman whose sister has given birth to a baby with Down syndrome is NOT at increased risk for having a baby with trisomy 21 or other trisomies, as Down syndrome is not inherited through siblings and the established risk factors are maternal age and a woman's own previous affected pregnancy—not her sister's pregnancy history.
Understanding the Genetics of Trisomy 21
The vast majority of Down syndrome cases (95%) result from full trisomy 21, which is not inherited but originates from errors in cell division during egg, sperm, or embryo development 1. These nondisjunction events occur sporadically and are not passed through family lines in the traditional sense 2.
Established Risk Factors for Trisomy 21
The only certain risk factors for having a child with Down syndrome are:
- Advanced maternal age at conception - This is the primary risk factor, with risk increasing exponentially after age 35, reaching approximately 1 in 356 at age 35 3
- History of a previous pregnancy with trisomy 21 in the same woman - Women under 25 years who have had a child with trisomy 21 show increased fetal loss rates (33.8%) in subsequent pregnancies, suggesting increased risk of recurrent aneuploidy 4
- Aberrant maternal chromosome 21 recombination patterns - These occur in the affected woman herself, not her relatives 1
Why a Sister's Affected Pregnancy Does Not Increase Risk
The SMFM/ACOG guidelines specifically identify who qualifies for increased-risk screening, and notably absent from this list is "family history of Down syndrome in a sibling's child" 5. The guideline criteria for increased risk include:
- Maternal age ≥35 years at delivery 5
- Fetal ultrasound findings suggesting aneuploidy 5
- History of previous pregnancy with trisomy in the same woman (not her sister) 5
- Positive aneuploidy screening results 5
- Parental balanced Robertsonian translocation 5
The emphasis on "previous pregnancy" refers to the woman's own obstetric history, not that of her siblings 5.
Clinical Management Approach
For a woman whose sister has had a baby with Down syndrome:
- Assess her individual risk factors - Focus on her own maternal age and obstetric history, not her sister's 3
- Offer standard screening based on her age and preferences - She should receive the same screening options as any woman her age: first-trimester combined screening, cell-free DNA screening, or second-trimester quad screen 6, 7
- Provide reassurance - Explain that her sister's affected pregnancy does not increase her personal risk, as trisomy 21 typically results from sporadic nondisjunction events 1
Important Caveats
The rare exception would be if there is a parental balanced Robertsonian translocation involving chromosome 21 in the family, which could be inherited and would increase risk 5. However, this would typically be identified through genetic testing of the affected child and would require:
- Karyotyping of the affected child to identify translocation Down syndrome (3-4% of cases) 2
- If translocation is confirmed, parental karyotyping to determine if either parent is a carrier 5
- If a parent carries the translocation, their children (the woman and her sister) would need testing 5
Without evidence of a familial translocation, the woman's risk remains based solely on her own maternal age and reproductive history 3, 1.