Brachytelephalangic dwarfism due to the loss of ARSE and SHOX genes resulting from an X;Y translocation

Here we report an 8-year-old male patient who had mesomelic shortening of f orearms and legs, brachytelephalangia and ichthyotic skin lesions. Chromoso mal analysis showed an X;Y translocation involving the short arm of the X c hromosome (Xp). Fluorescence in situ hybridization (FISH) and molecular stu dies localized the breakpoints on Xp22.3 in the immediate vicinity of the K AL gene demonstrating deletions of steroid sulfatase (STS), arylsulfatase E (ARSE), and short stature homeo box (SHOX) genes. It was suspected that th e patient was suffering from chondrodysplasia punctata because of a loss of the arylsulfatase E (ARSE) gene. However, no stippled epiphyses were to be seen in the neonatal radiograph. Interestingly, this patient is the first case with a proven loss of the ARSE gene without chondrodysplasia punctata, assuming that chondrodysplasia punctata is not an obligatory sign of ARSE gene loss. Brachytelephalangia was the only result of ARSE gene deletion in this case. The patient's mother also had dwarfism and showed Madelung deformity of the forearms. She was detected as a carrier of the same aberrant X chromosome. The male patient did not show Madelung deformity, demonstrating that Lerri -Weill syndrome phenotype may be still incomplete in children with SHOX gen e deletion. The wide clinical spectrum in the male and the Leri-Weill pheno type in his mother are the results of both a deletion involving several sul fatase genes in Xp22.3 and the SHOX gene located in the pseudoautosomal reg ion. Nevertheless, there is no explanation for the absence of chondrodyspla sia punctata despite the total loss of the ARSE gene. Further studies are necessary to investigate genotype/phenotype correlation in cases with translocations or microdeletions on Xp22.3, including the AR SE and the SHOX gene loci.