Subtelomeric Rearrangements in Patients with Recurrent Miscarriage

Objective The Subtelomeric rearrangements are increasingly being investigated in cases of idiopathic intellectual disabilities (ID) and congenital abnormalities (CA) but have also been suspected to be responsible for unexplained recurrent miscarriage (RM). We have noticed a higher risk of subtelomeric translocations in association with CA and ID. Such rearrangements can go unnoticed through conventional cytogenetic technique and cannot be detected even with high-resolution molecular cytogenetic techniques as Comparative Genomic Hybridization (array CGH) especially when DNA of stillbirth or families are not available. MaterialsAndMethods In this cross-sectional study, Fluorescent in Situ Hybridization (FISH), using ToTelVysion telomeric probes, was performed for 21 clinically normal couples, having at least two abortions and exhibiting a “normal” Karyotype. Around 62% had RM with a history of stillbirth or CA/ID and 38% had only RM. Results FISH detected one cryptic rearrangement between 3q and 4p chromosomes in the female partner of a couple (III:4) who presented a history of recurrent miscarriage and a family history of intellectual disabilities and congenital abnormalities 46,XX,ish t(3;4)(q28-,p16+;p16-,q28+)(D3S4559+,D3S4560-,D4S3359+; D3S4560+, D4S3359-,D4S2930+). Investigation of other members of the woman’s family showed that her sisters (III:6 and III:11) and her brother (III:8) were also carriers of the same subtelomeric translocation t(3;4)(q28;p16). Conclusion We conclude that subtelomeric FISH should be indicated in cases of recurrent miscarriages especially when couples have not only abortions but also at least one child with ID and or CA and or clinically recognizable syndromes. Being balanced and cryptic anomalies, subtelomeric fluorescent in situ hybridization is still the most suitable and useful tool to characterize such chromosomal rearrangements in RM couples to date.