title: Mesomelic and rhizomelic short stature: The phenotype of combined Leri-Weill dyschondrosteosis and achondroplasia or hypochondroplasia.
abstract: We studied two children with combined genetic skeletal disorders. Both had Leri-Weill dyschondrosteosis (LWD); one also had achondroplasia and the other had hypochondroplasia. Both had severe short stature and evidence of rhizomelia and mesomelia as well as other phenotypic features of their individual genetic disorders. Achondroplasia was due to the G380R FGF3R mutation and hypochondroplasia to a N540K mutation in the same gene. The patient with hypochondroplasia had a heterozygous SHOX deletion; no SHOX mutation was identified in the child with achondroplasia. The phenotypes of combined LWD and achondroplasia or hypochondroplasia appeared to be less than additive, suggesting that SHOX and FGFR3 act on overlapping pathways of bone growth and development.
authors.affiliation: Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. judith.ross@mail.tju.edu
authors.forename: Judith L
authors.initials: JL
authors.lastname: Ross
authors.forename: Gary
authors.initials: G
authors.lastname: Bellus
authors.forename: Charles I
authors.initials: CI
authors.lastname: Scott
authors.forename: Jack
authors.initials: J
authors.lastname: Abboudi
authors.forename: Giedre
authors.initials: G
authors.lastname: Grigelioniene
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Zinn
mesh_terms: D000130:Achondroplasia / Q000473:pathology; D001848:Bone Diseases, Developmental / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D010009:Osteochondrodysplasias / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D000074122:Short Stature Homeobox Protein
chemical_list: D018398:Homeodomain Proteins; D017468:Receptors, Fibroblast Growth Factor; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein; D004247:DNA; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3