Partial duplications of the short arm of the X chromosome are relatively rare and have been described in males and females. We describe a 4 10/12-year-old girl presenting with developmental delay, severe language retardation and minor anomalies with slightly elevated head circumference (+1.8 SD), prominent forehead, wide palpebral fissures and anteverted nares. No pigmentary dysplasia of the skin was present. The external genitalia were normal. The karyotype completed by cytogenetic analysis with the Whole Chromosome Painting probe of chromosome X revealed a de novo partial duplication of the short arm of an X chromosome. In order to further characterize the duplicated segment, we used a series of BAC probes extending from band Xp11.22 to Xp22.1. BACs from Xp11.23 to Xp11.4 were duplicated. The karyotype was finally defined as 46,X,dup(X)(p11p11).ish dup(X)(p11.23p11.4)(WCPX+,RP11-416I6++,RP11-386N14++,RP11-466C12++). The X-inactivation status was studied using the human androgen receptor (HUMARA) and the FRAXA locus methylation assay. Unexpectedly, the two X chromosomes were found to be randomly inactivated, in the proband. Indeed, usually, in women with structurally abnormal X chromosome, the abnormal X chromosome is preferentially inactivated and those patients share an apparent normal phenotype. So, we speculate that in the present case, the phenotype of the patient could be explained by a functional disomy of the genes present in the duplicated region. We will discuss the possible implication of these genes on the observed phenotype.
2008 Wiley-Liss, Inc.