Langer mesomelic dysplasia (LMD; MIM 249700) is characterized by hypomelia with severe hypoplasia of ulnae and fibulae, and bowed, thickened radii and tibiae, causing deformities of the hands and feet. LMD is caused by homozygous mutations in the SHOX/SHOXY (short stature homoebox) gene, of which bi-allelic mutations or gross deletions cause Leri-Weill dyschondrosteosis (LWD). The aim of our study was to determine the genetic etiology of LMD.
Our patient was a 16-year-old female with LMD, the second child of healthy first-cousin parents. She had micrognathia, disproportionate short stature with various musculoskeletal findings (absence of the distal flexion creases of the 3rd, 4th, and 5th fingers on the right hand and camptodactyly of the 3rd, 4th, and 5th fingers on the left ; tibial bowing). X-rays revealed hypoplasia of ulnae, fibulae, and the mandible.
Chromosome analysis and FISH investigation by using SHOX gene probe revealed normal results. The intended sequence analysis with the aim of investigating possible mutations failed due to obtaining PCR amplification with no product. Array comparative genomic hybridization (a-CGH) study showed a 174 kb homozygous deletion, encompassing the SHOX gene. Proband’s parents were heterozygous for the same deletion by a-CGH.
The addition of the a-CGH study to the algorithm is also important in terms of diagnostic contribution in the search for mutations in the SHOX/SHOXY gene responsible for the formation of the LMD phenotype.