Discovering a familial Xp11.4 microduplication: Does the mother matter?

Interstitial duplications of the short arm of the X chromosome have been rarely described, especially in males. Usually boys present mental retardation, multiple congenital abnormalities and short stature. We describe two sons one with a 2q37.3 deletion and a Xp11.4 duplication and the other with Xp11.4 duplication only, identified by array-CGH. They both presented a phenotype characterized by poor growth, mild facial dysmorphisms, autism and developmental delay. The 2q37.3 identified chromosomal anomaly was inherited from the healthy father and included approximately 8 known genes, while the Xp11.4 duplication resulted inherited from the healthy mother and involved 13 known genes. Of these TSPAN7 and CASK, localized on Xp11.4, genes are of special interest. The alteration on the X chromosome could be more related to the clinical feature presented by the two brothers, while the anomaly on the chromosome 2 is more likely a polymorphism or might influence the phenotype correlated to the Xp11.4 duplication. The healthy phenotype of the mother could be explained by X chromosome inactivation (XCI) phenomenon.