A Systematic Review of Reproductive Counseling in Cases of Parental Constitutional Reciprocal Translocation (9;22) Mimicking BCR-ABL1

Abstract

We aim to determine the spectrum of cytogenetic abnormalities and outcomes in unbalanced offspring of asymptomatic constitutional balanced t(9;22) carriers through a systematic literature review. We also include a case of a constitutional balanced t(9;22) carrier from our institution. Among the 16 balanced t(9;22) carriers in our review, 13 were maternal and 3 were paternal. Of the 15 unbalanced translocation cases identified, 13 were live births, one was a missed abortion, and one resulted in pregnancy termination. The spectrum of established syndromes reported among the live births was the following: trisomy 9p syndrome (6/13), dual trisomy 9p and DiGeorge syndrome (3/13), dual 9q subtelomere deletion syndrome and DiGeorge syndrome (1/13), 9q subtelomere deletion syndrome (1/13), and DiGeorge syndrome (1/13). One unbalanced case did not have a reported syndrome. The phenotype of the unbalanced cases included cardiac abnormalities (5/13), neurological findings (7/13), intellectual disability (6/10), urogenital anomalies (3/13), respiratory or immune dysfunction (3/13), and facial or skeletal dysmorphias (13/13). Any constitutional balanced reciprocal t(9;22) carrier should be counseled regarding the increased risk of having a child with an unbalanced translocation, the spectrum of possible cytogenetic abnormalities, and predicted clinical phenotype for the unbalanced derivative.

Keywords: Philadelphia chromosome; chromosome aberrations; chromosome breakpoints; reproductive counseling; translocation.

FIGURE 1

A reciprocal translocation of t(9;22)(q34;q11.2) involving neither the ABL1 locus at 9q34 nor the BCR at 22q11.2 was seen in each of the metaphases analyzed. (A) Interphase FISH study showed a normal signal pattern; probes for the ASS1*, ABL1 and BCR were labeled in aqua, red, and green, respectively. (B) Metaphase FISH study showed an abnormal hybridization pattern with no translocation of BCR/ABL1 observed. The arrows are pointing to the derivative chromosome 9 [der(9)] carrying a signal for BCR but no signals for the ASS1 and ABL1, the derivative chromosome 22 [der(22)] carrying signals for the ASS1 and ABL1 but no signal for the BCR, the normal chromosome 9 [chr 9] and the normal chromosome 22 [chr 22]. (C) Karyogram exhibited an apparently balanced reciprocal translocation between the long arm of chromosome 9 at 9q34 and the short arm of chromosome 22 at 22q11.2, with morphology indistinguishable from the Philadelphia translocation. (D) A schematic illustration of the normal copies of chromosomes 9 and 22 as well as the derivative chromosomes 9 and 22 resulted from the reciprocal translocation. The breakpoints at each derivative chromosome involved were located at the vicinity but proximal to the loci involved in the Philadelphia translocation. *ASS1 is a control probe at 9q34 overlapping the ABL1 probe.

FIGURE 2

Flow diagram of studies identified in the systematic review.