Homozygous deletion of SHOX in a mentally retarded male with Langer mesomelic dysplasia

Editor—Langer mesomelic dysplasia (LMD) is a rare skeletal dysplasia characterised by severe short stature owing to shortening and maldevelopment of the mesomelic and rhizomelic segments of the limbs. Associated malformations are rarely reported and intellect is normal in all affected subjects reported to date.1-5 The clinical observation has been made that the parents of subjects with LMD often have short stature, most commonly with the associated clinical and radiographic appearances of Leri-Weill dyschondrosteosis (DC).6 This dominantly transmitted condition is characterised by moderate short stature predominantly because of short mesomelic limb segments. It is often associated with the Madelung deformity of the wrist, comprising bowing of the radius and dorsal dislocation of the distal ulna. This observation has led to the suggestion that LMD is the homozygous expression of the mutant gene for DC.5 6 Shears et al 7 and Belin et al 8 recently showed that the molecular defect in DC is mutation within or deletion of the SHOX gene located within the primary pseudoautosomal region of the X and Y chromosomes. Deletion or mutation of SHOX has also been shown to lead to short stature without overt bone dysplasia.9 10 Belin et al 8 documented the molecular analysis of a 24 week fetus of a female patient with DC and a pseudoautosomal deletion encompassing SHOX . The fetus had a 45,X karyotype and the radiographic appearances of LMD. They showed that the Xp chromosomal haplotype at the SHOX locus retained by this fetus was the maternal one, encompassing the deleted SHOX gene, rendering the fetus nullizygous for SHOX . Shears et al 7 reported that deletions of SHOX alleles were derived from both parents in a 20 week fetus with radiographic appearances of LMD. These findings in fetuses were the first molecular evidence …