European Human Genetics Conference 2014, Milan, Italy, 31 May - 03 June 2014, vol.22, no.1, pp.404
Langer mesomelic dysplasia (LMD) is characterized by hypomelia with severe
hypoplasia of ulnae and ibulae, 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
heterozygous mutations or deletions cause Leri-Weil Dysplasia (LWD).
Phenotype of LWD can be incomplete between and within families. We present
a 13 year old female with LMD, the second child of healthy irst cousin
parents. She had micrognathia, disproportionate short stature with various
musculoskeletal indings (absence of the distal lexion creases of the 3rd,
4th, 5th ingers on the right, camptodactyly of the 3rd, 4th, 5th ingers on
the left, tibial bowing). X-rays revealed hypoplasia of ulnae, ibulae and the
mandible. Chromosome analysis and FISH investigation by using SHOX gene
probe revealed normal results. Sequence analysis failed due to unsuccessful
PCR ampliications. 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. FISH
was uninformative, because there was no difference between the intensity
of the signals on both chromosomes. Since the primers used were located
within the deleted region, molecular studies could not be performed. A-CGH
proved to be the most powerful diagnostic tool in this case.