title: Molecularly proven hypochondroplasia with cloverleaf skull deformity: a novel association.
abstract: We report on a case of cloverleaf skull deformity in a patient with hypochondroplasia, a disorder which has not been previously associated with this anomaly. Hypochondroplasia is a bone dysplasia caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Cloverleaf skull is a trilobar skull deformity which is etiologically and genetically heterogeneous and occurs in association with a number of disorders which result from mutations in the fibroblast growth factor receptor genes. Our patient demonstrated one of the common FGFR3 mutations identified in hypochondroplasia, a C-to-A change at nucleotide 1620 (C1620A) in the tyrosine kinase domain. The occurrence of a cloverleaf skull deformity appears to represent an example of variable expressivity in hypochondroplasia and suggests that additional factors other than a specific mutation can modify the phenotype in this disorder. In addition, identification of another FGFR mutation associated with cloverleaf skull further illustrates the genetic heterogeneity of this anomaly.
authors.affiliation: Child Evaluation Center, Department of Pediatrics, University of Louisville, KY 40202, USA.
authors.forename: B
authors.initials: B
authors.lastname: Angle
authors.forename: J H
authors.initials: JH
authors.lastname: Hersh
authors.forename: K M
authors.initials: KM
authors.lastname: Christensen
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics*; D002648:Child; D006801:Humans; D008297:Male; D010009:Osteochondrodysplasias / Q000235:genetics*; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012886:Skull / Q000002:abnormalities
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3