Influence of advanced age of maternal grandmothers on Down syndrome.
BACKGROUND
Down syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92-95%), mosaic trisomy 21 (2-4%) and translocation (3-4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction.


METHODS
We investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression.


RESULTS
Out of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years) born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds) of birth of DS baby increases by 30%.


CONCLUSIONS
Besides the known risk factors, mother's age, father's age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome.
Malini
Suttur S
SS
Human Genetics Laboratory, Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore 570 006, India. rnallur@sancharnet.in
Ramachandra
Nallur B
NB
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004314:Down Syndrome / Q000453:epidemiology*; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008423:Maternal Age; D010331:Paternal Age; D010375:Pedigree; D012307:Risk Factors