Atypical Chromosome X-inactivation

In females, because there are 2 X chromosomes, one of them undergoes a phenomenon of X-inactivation where it becomes silenced and is not expressed. The chromosome that becomes silenced in each cell is usually random. However, when a translocation involving the X chromosome occurs, the structurally abnormal X chromosome is usually preferentially inactivated. If, due to translocation, the autosomal segment is replaced onto the X chromosome, inactivation may also spread to this autosomal segment. As a result, the patient may have a functional monosomy for the inactivated part of the autosome (usually with functional disomy for the segment of X-chromosome), even though he/she may have a formally balanced karyotype.

The authors describe a girl with significant developmental delay, microcephaly, hypoplastic cerebellar vermis, neuronal heterotopias (abnormal neuron migration), ventricular septal defect and facial dysmorphism (bilateral epicanthic folds, wide nasal bridge, broad nasal tip, broad philtrum, thick and everted lower lip). The girl had a cytogenetically balanced translocation t(X;6)(p22.11;q27), but the derivative X chromosome was inactive in all cells. Spread of inactivation to the part of 6q explains the clinical abnormalities in this patient. Functional disomy Xpter-p22.11 is most likely not responsible for the clinical manifestations in this patient. The girl also had a microdeletion in 6q21, involving only two genes, but this microdeletion is most likely a benign variant.

Functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 due to X;6 translocation with an atypical X-inactivation pattern Podolska, A et al., Am J Med Genet A. 2017 May;173(5):1334-1341. doi: 10.1002/ajmg.a.38183.