| Summary: | Abstract Background Down syndrome (DS) is a common numerical chromosome disorder that has its burden on both family and community. The well-known risk factor for chromosome 21 nondisjunction is advanced maternal age which failed to explain the occurrence of Down syndrome born to mothers less than 35 years. This study aimed to assess the effect of demographic data (consanguinity, residency area, and socioeconomic state) and chromosome/chromatid breaks as biomarkers for genome integrity on the susceptibility of young mothers to have a child with Down syndrome. Results Fifty mothers with a history of at least one DS pregnancy before the age of 35 were compared to 50 control mothers. There was a significant increase in DS births in consanguineous parents (46%) compared to 20% in non-consanguineous ones (OR = 3.40; 95% CI = 1.4–8.20, P = 0.006). Young mothers with DS children were more likely to be from rural areas (60%) than urban areas (40%) (OR = 2.66; 95%, CI = 1.18–5.98, P = 0.017) and of a low socioeconomic status (62%) rather than a high socioeconomic status (38%) (OR = 3.80; 95%, CI = 1.65–8.74, P = 0.001). Chromosome/chromatid breaks were detected in 76% of DS young mothers and 32% of control mothers (P < 0.001). There was an odds ratio of chromatid breaks of 8.50 (3.411–21.17) and chromosome breaks of 3.93 (1.40–11.05) with significant difference between the studied groups (P < 0.001 and P = 0.009 respectively). Conclusion In addition to advanced maternal age, consanguinity, residency in rural areas, and low socioeconomic status could be considered as possible risk factors for Down syndrome. The high frequency of chromosome/chromatid breaks in young mothers with a previous history of DS children highlights the impact of genome integrity on the tendency to chromosome 21 nondisjunction. These findings are valuable in predicting having a Down syndrome baby and providing proper genetic counseling for high-risk families.
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