“Balanced” karyotypes in six abnormal offspring of balanced reciprocal translocation normal carrier parents

Abstract

Among 6800 consecutive blood samples studied for clinical cytogenetic diagnosis, we identified 30 families in which one parent of the proband had a balanced reciprocal autosomal translocation (excluding Robertsonian rearrangements). Twenty-eight of the 30 families had a malformed and/or mentally retarded proband: 19 with an unbalanced derived chromosome, 3 with abnormalities involving chromosomes other than those in the translocation, 5 with a "balanced" reciprocal translocation, and 1 with a normal karyotype. We hypothesize that the latter 6 affected probands with "balanced" karyotypes could be abnormal due to submicroscopic deletions and duplications as was originally suggested by Jacobs [1984]. Particularly in these 6 families, 83% of translocation breakpoints were associated with fragile sites, more than expected by chance (P < 0.025). This supports the report of an association between fragile sites and constitutional chromosome breakpoints by Hecht and Hecht [1984]. To explain these findings, we propose that autosomal fragile sites are unstable areas which predispose to breaks and unequal crossing over near the fragile site breakpoints creating minute duplications and deletions. Consequently, newborn infants inheriting a seemingly "balanced" karyotype from a normal parent with a balanced reciprocal translocation may still be at an increased risk of being malformed and/or developmentally delayed because of submicroscopic chromosomal imbalances.

COFS syndrome with familial 1;16 translocation

“…Familial inherited balanced translocations with abnormal phenotype are not common. However, Wenger et al (1995) reported balanced karyotypes in six abnormal offspring of balanced reciprocal translocation normal carrier parents. Reid et al (1993) reported familial translocation at 7p22 in Saethre-Chotzen syndrome.…”

De Novo Three-Way Chromosome Translocation [46,XX,t(1;20;4) (p32;q12;q32)] in a Patient with Developmental Delay: A Case Report

“…Balanced chromosomal translocations may cause damage or alteration of the functional genes at the breakpoints of the defective chromosomes resulting in the disease phenotype (10). It was described previously that children who inherit reciprocal balanced translocation from one of the parents show association with congenital malformation (11)(12)(13). The risk for offspring of a carrier of a balanced CCR is difficult to estimate (14).…”

Familial translocation t(Y;15)(q12;p11) and de novo deletion of the Prader-Willi syndrome (PWS) critical region on 15q11-q13

“…There is also ample precedent for the association of abnormal phenotypes with apparently balanced familial translocations, Robertsonian or reciprocal [Fryns et al, 1991;Wenger et al, 1995]. Mechanisms for the production of such phenotypic abnormalities include cryptic translocations [Wagstaff and Hemann, 1995], submicroscopic deletions or duplications due to unequal crossing-over, uniparental disomy of one of the chro- mosomes involved [Engel and DeLozier-Blanchet, 1991], and disruption of imprinting [Weksberg et al, 1993].…”