Novel variant in HDAC8 gene resulting in the severe Cornelia de Lange phenotype

Cornelia de Lange syndrome (CDLS) is a clinically and genetically heterogeneous developmental disorder characterized by multiple malformations. Primarily, affected individuals have unique and recognizable dysmorphic facial features, cleft palate, distal limb defects, growth retardation, and developmental delay. However, also milder, as well as slightly phenotypically different forms exist. We described herein a patient with CDLS5, an X-linked form, caused by mutations in the HDAC8 gene inherited form the mosaic mother. Analysis of results from whole exome sequencing identified two variants with possible impact on the phenotype. Of them, hemizygous variant (c.938G>A, p.Arg313Gln) inherited from the mosaic mother, was further proved to lead to disease in the proband. Our intention was to delineate this syndrome but also point out the clinical course of the disease, which only in combination with a facial phenotype allow for verification of exome sequencing result.