Genomic rearrangements play a major role in the pathogenesis of human genetic diseases. Nonallelic homologous recombination (NAHR) between low-copy repeats (LCRs) that flank unique genomic segments results in changes of genome organization and can cause a loss or gain of genomic segments. These LCRs appear to have arisen recently during primate speciation via paralogous segmental duplication, thus making the human species particularly susceptible to genomic rearrangements. Genomic disorders are defined as a group of diseases that result from genomic rearrangements, mostly mediated by NAHR. Molecular investigations of genomic disorders have revealed genome architectural features associated with susceptibility to rearrangements and the recombination mechanisms responsible for such rearrangements. The human genome sequence project reveals that LCRs may account for 5% of the genome, suggesting that many novel genomic disorders might still remain to be recognized.

Pure trisomy due to nondysjunction of chromosome 21 is responsible for 96% of Downs with a recurrence risk of less than 1%. Parental karyotype is not required in nondysjunction type of trisomies. Majority of fetuses with Trisomy 13, 18, monosomy XO and triploidy display major malformations on USG. Recurrence for all of the above nondysjunction numerical aberration is low. Hence, pregnancies with previous history of any of the above confirmed on fetal karyotype, can be followed up by serial ultrasound scans. Translocation of chromosome 21 (4% of Downs), the recurrence risk varies between 10-25% if one parent is a carrier of a translocation. The risk of unbalanced translocation in the offspring will depend on the type of translocation in the parents, which parent is involved and whether translocation is between homologous or non homologous chromosome. Once an unbalanced translocation in the fetus / child has been identified, parental karyotype is essential. More than 50% of translocations in fetus occur denovo. So if parents have a normal karyotpe, no matter what the translocation in the fetus, recurrence risk is minimal <1%.

Preimplantation genetic diagnosis (PGD) by fluorescence in situ hybridization (FISH) for a Robertsonian translocation was carried out in a young couple with 2 missed abortions. The wife had a karyotype of 45,XX,rob(13;14)(q10;q10). One normal embryo was obtained in the first cycle and transferred at the blastocyst stage, resulting in a successful pregnancy. This is the first reported case of PGD for a translocation from India, resulting in an ongoing pregnancy.

Rh isoimmunization still remains an important preventable cause of perinatal mortality and morbidity. The approach to its management has changed over the past two decades. Survival has improved dramatically in affected babies. We compared the presentation, type of invasive procedures and overall survival in cases referred to a tertiary teaching hospital during the 14 year period 1994 to 2001 (study period I) with the period 2002 to 2008 (study period II). In study period I, out of 104 isoimmunized pts, 161 amniocentesis procedures were performed in 60 patients throughout pregnancy. 50 of these underwent 120 total transfusions. Total procedures per patient were 4.68. In study period II, out of 33 isoimmunized pts needing interventions, 11 pts underwent amniocentesis, 3 underwent cordocentesis. Colour Doppler ultrasonography was performed periodically to determine the middle cerebral artery peak systolic velocity. This practically eliminated the need for amniocentesis to determine the timing of intrauterine transfusions. 29 of these were subjected to 77 total transfusions. Thus, total procedures per patient were 2.7. Overall survival in Study period I was 52% as compared to 79% in study period II. The difference is statistically significant for both hydropic and non-hydropic groups (P<0.001). The possible reasons contributing to improved survival were analyzed.

The Fragile-X syndrome (FXS), an X-linked disorder, is recognized as the second common cause of mental retardation after Down syndrome. It is associated with a variety of neurobehavioral deficits, including cognitive dysfunction, attention-deficit /hyperactivity, autism spectrum disorders, and other emotional problems. FXS is caused by full mutation (> 200 CGG repeats) in FMR1 (fragile X mental retardation 1 gene). This dynamic mutation of FMR1 is due to progressive expansion of polymorphic (CGG)n trinucleotide repeats located in the promoter region of the FMR1 at Xq27.3 causing decreased or absent levels of fragile X mental retardation protein (FMRP). The smaller expansion (55-200 CGG) of FMR1 is termed a premutation, often found in mothers of FXS and also in premutation carriers with varying degrees of physical phenotypes and intellectual impairment correlated with the magnitude of FMRP deficit. Both full mutation and premutation makes FXS a family concern as an array of disabilities are seen throughout multiple generations. The aim of the study was thus to establish the polymerase chain reaction (PCR)-based method as a routine screening method for rapid detection of FXS. In view of this, total 720 MR children were selected for cytogenetic and further molecular investigation to check the reliability of the PCR method. The chromosomal analysis conducted in 443 children revealed 20 (4.5%) subjects with fragile site on X-chromosome, characteristic of FXS. Molecular study conducted on 12/65 cases showed (18.46%) to be positive by PCR technique and was confirmed by Southern Blotting. The clinical and dysmorphic features though well-described, are often mild and subtle; as a result go unnoticed by the clinicians. It is therefore important for a clinician who is not so equipped with genetic knowledge in India, to address the issues of transmission and genetic counseling to family members emphasizing the genetic testing in mental retardation (MR), associated learning and behavioral problems. This relatively simple and accurate molecular test was used to screen all patients with unexplained mental retardation/ learning impairment for FXS. The detection of FMR1 mutation was found helpful in informed genetic counseling for medical management, prenatal diagnosis and follow-up.