Apert and Crouzon syndromes: clinical findings, genes and extracellular matrix

• Published in: The Journal of craniofacial surgery Vol. 16; no. 3; p. 361
• Main Authors: Carinci, Francesco, Pezzetti, Furio, Locci, Paola, Becchetti, Ennio, Carls, Friedrick, Avantaggiato, Anna, Becchetti, Alessio, Carinci, Paolo, Baroni, Tiziano, Bodo, Maria
• Format: Journal Article
• Language: English
• Published: United States 01.05.2005
• Subjects: Acrocephalosyndactylia - genetics; Amino Acid Substitution; Craniofacial Dysostosis - genetics; Extracellular Matrix - chemistry; Genes, Dominant; Humans; Osteogenesis - genetics; Point Mutation; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Fibroblast Growth Factor - genetics
• DOI: 10.1097/01.SCS.0000157078.53871.11
• ISSN: 1049-2275

Apert and Crouzon syndromes are well known craniostenosis. In the last 10 years several studies were performed to provide a better understanding of the etiology and pathogenesis of these diseases. Both have an autosomal dominant mode of transmission, and a mutation in the gene encoding for the fibroblast growth factor receptor 2 (FGFR2) is the cause in most patients. However, the fact that the same mutation can produce a wide range of phenotypic expression makes the mechanism of anomalous development more complex. The extracellular matrix (ECM) is composed of proteins, glycosaminoglycans, and cytokines that are secreted in an autocrine and paracrine manner and are able to modify the ECM. Fibroblast growth factors are complexed with heparan sulfate, a component of the ECM, before binding the FGFR2. Data exist about different expressions of cytokines and ECM macromolecule in craniostenosis-derived fibroblasts and osteoblasts. Changes in ECM composition could explain the altered osteogenic process and account for pathologic variations in cranial development in addition to the FGFR2 mutations.