We observed an increased frequency of binucleated micronucleated lymphocytes in mothers who had a Down syndrome (DS) child before 30 years of age and the fluorescence in situ hybridization analysis revealed that micronuclei were mainly originating from malsegregation chromosome 21.The present study included 62 Egyptian young mothers (age < 30 y) ,free from any chronic disease, not taking any regular drugs, there were divided into 2 groups: group 1; 22 mothers of classic Down syndrome children and group 2; 40 healthy Egyptian matched females as control group. Cases were recruited from the Genetics outpatient clinic of National Research Centre and Children's Hospital, Cairo University. Statistical analysis for malsegergation of chromosome 21 using FISH probe revealed high susceptibility of malsegergation (p=0.0001) in young mother of Down syndrome children compared to controls mothers.