Termination of Pregnancy for an 11q Terminal Deletion Incidentally Diagnosed Prenatally; Jacobsen Syndrome Penetrance and Ethical Dilemmas

Abstract

The currently noted boost of de novo microdeletions has been partly attributed to the relevant increase of mean paternal age at the time of first child acquisition. The simultaneous widespread implementation of molecular techniques for prenatal karyotyping has revealed distinct deletion aberrations of uncertain clinical significance. Recent research has failed to confirm the intrinsic correlation between implicated genome fragment and extent of phenotypic abnormality. We present a case of an 11q terminal deletion detected incidentally in a fetus displaying no evidence of anomaly during successive detailed ultrasound anatomy scans. The genotype corresponds to Jacobsen syndrome exhibiting great heterogeneity attributed to epigenetic modifications. For example, homeostatic mechanisms at the level of transcription or translation can mitigate the phenotypic effects of a deletion. However, unmasking of a recessive mutation on the non-deleted homologous chromosome can amplify phenotypic abnormalities. Genetic counselling is a priori considered as a challenging process taking into consideration that the spectrum of normal is subjectively defined by the personal perspectives of the individual. Undoubtedly, it becomes even more demanding if no tangible deformity can be depicted. Reporting bias lurks when genetic consultation is mainly based on previously recorded phenotypes, since less affected persons are unlikely to be detected.