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Trisomy recurrence: a reconsideration based on North American data.

Dorothy Warburton¹, Louis Dallaire, Maya Thangavelu

¹Department of Genetics, Columbia University, New York, NY, USA. cuh@cancercenter.columbia.edu

American Journal of Human Genetics

|July 13, 2004

Summary

This study found that women with a history of trisomy have an increased risk of having another trisomy, either the same or a different one. This suggests some women have a higher underlying risk for nondisjunction.

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Area of Science:

Genetics
Reproductive Medicine
Prenatal Diagnosis

Background:

Reliable data on the recurrence risk of specific trisomies and different trisomies are limited.
Understanding recurrence risks is crucial for genetic counseling and reproductive decision-making.

Purpose of the Study:

To investigate the recurrence risk of the same trisomy (homotrisomy) and different trisomies (heterotrisomy) after an initial trisomy diagnosis.
To determine if maternal age influences the risk of trisomy recurrence.

Main Methods:

Retrospective analysis of prenatal diagnoses from Hopital Sainte-Justine and Genzyme.
Calculation of standardized morbidity ratios (SMR) comparing observed trisomy rates with expected age-specific rates.
Stratification of SMRs by recurrence type (homotrisomy vs. heterotrisomy) and maternal age.

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Main Results:

An increased SMR for homotrisomy was observed after trisomy 21 (SMR=2.4), particularly in younger mothers (<30 years, SMR=8.0).
A significantly increased SMR for heterotrisomy was found after trisomy 21 (SMR=2.3) and across all viable trisomies (SMR=1.6).
Increased risk for heterotrisomy was not dependent on maternal age at the first trisomy diagnosis.

Conclusions:

Women with a history of trisomy have an elevated risk for subsequent trisomies, both identical and different.
The findings support the hypothesis that some individuals possess a constitutional predisposition to nondisjunction.
These results have implications for genetic counseling, emphasizing individualized risk assessment beyond maternal age alone.