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.

We report on the case of a young woman with a de novo 20p11.21p11.23 deletion, discovered by array-CGH. She has behavioral troubles with autistic traits, intellectual disability, panhypopituitarism, severe hypoglycemia, epilepsy, and scoliosis. The majority of the reported 20p deletions are located on the 20p12 region, covering the JAG1 gene responsible for the Alagille syndrome. More proximal deletions are even rarer, with very few cases described in the literature to date. The deletion carried by our patient is, to our knowledge, the smallest described de novo proximal 20p11.2 deletion. It was first discovered by 0.5 Mb BAC array-CGH, further delineated using an oligonucleotide array, and finally confirmed by fluorescence in situ hybridization. The deletion is 4.22 Mb in size, with the exact location on chr20: 19.810.034-24.031.344 (Feb. 2009, GRCh37/hg19). In light of the other reported cases that display genomic and phenotypic overlap with our patient, we discuss the phenotype of our patient, in order to further delineate the 20p proximal deletion phenotype. We propose a minimal critical region responsible for panhypopituitarism with global developmental delay, intellectual disability, scoliosis and facial dysmorphism. Moreover, considering the deleted genes, we highlight the impact of the deletion of this minimal critical region on the Shh signaling pathway.

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