MOLECULARLY PROVEN HYPOCHONDROPLASIA WITH CLOVERLEAF SKULL DEFORMITY - A NOVEL ASSOCIATION

We report on a case of cloverleaf skull deformity in a patient with hy pochondroplasia, a disorder which has not been previously associated w ith this anomaly. Hypochondroplasia is a bone dysplasia caused by muta tions in the fibroblast growth factor receptor 3 (FGFR3) gene. Cloverl eaf skull is a trilobar skull deformity which is etiologically and gen etically heterogeneous and occurs in association with a number of diso rders which result from mutations in the fibroblast growth factor rece ptor 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 expressivi ty in hypochondroplasia and suggests that additional factors other tha n a specific mutation can modify the phenotype in this disorder. In ad dition, identification of another FGFR mutation associated with clover leaf skull further illustrates the genetic heterogeneity of this anoma ly.