Estudo molecular das craniossinostoses sindrômicas: Crouzon, Pfeiffer e Saethre-Chotzen"

Abstract

Capítulo 1-Introdução geral e objetivos _____________________________ 04 1.1-Introdução Craniossinostoses___________________________________ 05 1.1.2-Craniossinostoses Sindrômicas _______________________________ 08 1.2-Aspectos clínicos das síndromes de craniossinostoses mais comuns _________________________________________________ 10 ABSTRACT Craniosynostosis, defined as the premature fusion of one or more cranial suture, are a very heterogeneous group of disorders, with an occurrence of about 1: 2000 live births. Except for rare syndromes, such as Apert, most of the cranioysnostotic conditions are characterized by wide clinical variability and genetic heterogeneity. Craniosynostosis can be classified into non syndromic forms-premature suture fusion is the only clinical alteration, and syndromic ones-premature cranial suture fusion associated with other anomalies. Apert, Pfeiffer, Crouzon and Saethre-Chotzen are the most common syndromic forms of craniosynostosis. The mutational mechanism is identified in approximately 58% of patients with Crouzon syndrome: FGFR2 mutations account for most of the cases (more than 80%) while mutations in TWIST1 and FGFR3 causes the remaining of them. Therefore, about 42% of the cases with clinical characteristics of Crouzon syndrome do not harbor mutations in any of these 3 genes and other mutational mechanisms might be responsible for the phenotype. Approximately 45% of Pfeiffer syndrome cases is not caused by mutations in the FGFR1 or FGFR2 genes, thus also suggesting genetic heterogeneity for this phenotype. On the other hand, all cases with Apert syndrome are caused by specific mutations in FGFR2. FGFR2 mutations show a partial genotype-phenotype correlation; however, severe cases, such as Pfeiffer types II and III are still very poorly characterized.