Clinical and genetic aspects of Marfan syndrome and familial thoracic aortic aneurysms and dissections

Abstract

This thesis concerns the clinical and genetic aspects of familial thoracic aortic aneurysms and dissections, in particular in Marfan syndrome. It includes the Dutch multidisciplinary guidelines for diagnosis and management of Marfan syndrome. These guidelines contain practical directions for referring physicians and specialists involved in the recognition, diagnosis, monitoring and treatment of Marfan syndrome. Furthermore, the revised Ghent nosology for Marfan syndrome, established by an international panel of experts, is presented. One chapter concerns a specific subgroup of missense mutations in FBN1 that are predicted to substitute the first aspartic acid of various calcium-binding Epidermal Growth Factor-like (cbEGF) fibrillin-1 domains. One of the mutations was found in a homozygous state in three cases from a large consanguineous family. A series of ten patients carrying a whole-gene deletion of one allele of FBN1 is described in another chapter. In a further chapter a three-generational family is discussed with family members at risk for serious aortic disease as a result of an interstitial deletion of chromosome 15 that disrupts SMAD3. Finally two unrelated children with classic Marfan syndrome and recurrent intracranial hypertension are described.