Down syndrome (DS) with trisomy (T21) is one of the most common aneuploidy in humans associated with mental retardation and develop-mental delay with the incidence of 1 per 920 births in India(1,2). The extra copy of chromosome 21 in DS children occurs as a free chromosome, part of Robertsonian (RT) fusion chromosome or in rare instances as a part of reciprocal translocation. The present study is aimed to document the types of cytogenetic abnormality in DS children and their relation to maternal age.

The study included 382 children in the age range of 2 days to 14 yr. They were referred between the periods of 1995 to 2006 for cytogenetic analysis to confirm the clinical diagnosis of DS.

Chromosome preparation was carried out from 3-4 mL of peripheral blood collected in sodium heparine in all subjects. Routinely, Giemsa (GTG) banding technique was performed to identify the chromosomes. Additional banding techniques like Centromeric (CGB) and NOR were used to confirm the structurally alerted chromosomes. In each case, 25-50 metaphases were examined and 3-5 cells were photographed and karyotyped. In cases of mosaicism, 50 to 100 metaphases were scored. Parents of children having structural anomalies were investigated to rule out the origin of altered chromosome.

The abnormal karyotypes are listed in Table I. Translocation accounted for 34 (8.9%) cases; maternal and paternal inheritance was seen in 6 and 3 cases, respectively; parental karyotype was normal in 12 cases suggesting de-novo origin. Parents of remaining 13 cases denied investigations. The overall male: female (M : F) sex ratio in this study was 2.3 : 1. There was no marked difference in the mean maternal age of either group. The birth frequency of DS babies in younger mothers (<35 yrs) is 91.6% compared to older mothers (>35 yrs) (Table II).

The frequency of free T21 observed in the present study is the most common and seen in 84.8% of cases which is consistent with Jacob et al. (84.6%) (3) and near to 87.9%(4).

RT is the second most and comprises of 8.9% and remain the highest among the larger series reported till date i.e., 3.8%(5) and 4.4%(4) from India. Familial inheritance in RT is seen in one quarter whereas in remaining it arises as a de-novo (6). In the present study, 3/13 cases with t (14; 21) showed maternal inheritance. In one of these, mother was subjected to CVS in her subsequent pregnancy and the karyotype was T21 in translocated form. This shows that mother transmitted the translocation in an unbalanced state to the offspring. The recurrence risk is <1% if the translocation is de-novo. In case of familial RT DS, the genetic risk for female carrier to have a live born child with translocation DS is about 10%, which increases to 15% at amniocentesis. For male carrier the recurrence risk to have a child with translocation DS is about 1%(7).

The homologous translocation (21q21q) is one of the most common chromosomal rearrangements in DS. An interesting observation was seen in one case where karyotypic analysis showed a "mirror" duplication of #21 which confirmed to be of paternal origin. This confirms that most de-novo rearrange-ments (21q21q) are isochromosomes derived from a single parental #21 and only small proportion is consistent with true RT(8,9).

Thus in DS, free T21, RT and mosaicism are the classical anomalies. Nonetheless in the last few years, non-classical DS karyotype have been reported in major DS studies with frequency ranging from 0-1.2% (5,10). Our data of 2.4% is higher than that previously reported. It is important to consider such non-classical DS cases in genetic counseling and provide precise recurrence risk for such distinct groups.

Though the advance maternal age is an established risk factor for DS, present study has shown increased number of DS babies born to the young mothers as more number of pregnancies occurs in this reproductive age group. This could either be due to MTHFR gene polymorphism(11) and/or nutritional factor(12). Higher incidence of free trisomy in the elderly mother reflects the meiotic error as the common cause in the present study (93 vs 84%). On the other hand, translocation DS was more common in younger mother in contrast to elder mothers (10 vs 4%) reflecting likely cause of parental origin that provides important information for genetic counseling to the family.

Our sincere thanks to all staff of Genetics Center, Sejal, Rashi and Pooja for compilation of the data and all referring doctors, which has made this study possible.