Phenotype Variations in a Family with Various Rearrangements in the Locus of the SHOX Gene

The SHOX gene is located on both sex chromosomes, X and Y, within the pseudoautosomal region 1 (PAR1). Gross deletions at the SHOX locus lead to protein insufficiency and are manifested by growth disorders such as Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia (LMD), and idiopathic short stature (ISS). In cases of the SHOX gene duplication, the phenotype may range from tall to short stature and LWD. This study describes a family with various SHOX locus alterations and diverse phenotypic manifestations. The proband inherited both deletion and duplication in the SHOX locus from her parents and shows typical features of LWD. The proband’s father carries SHOX gene deletion and displays Madelung’s deformity but normal height. The proband’s mother has SHOX gene duplication without any abnormalities in phenotype. One of the proband’s sons inherited deletion, while the other inherited duplication of the gene. Some family members also have the c.845_851dup variant in the CYP26C1 gene, previously described as a modifier of the SHOX gene. It is difficult to assess its effect. At present, it is not possible to predict the future phenotype of the proband’s children due to the high phenotypic variability associated with SHOX locus alterations.