Date of Award

4-12-2009

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Douglas Ross

Abstract

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu Syndrome is a phenotypically variable genetic disorder of angiogenesis. Many ethnicities are affected though generally the disease is believed to be most common in the Caucasian population (1). Originally incidence of HHT was estimated at 1-2 per 100,000; however, more recent epidemiological studies have been performed indicating that the disease is more common with an incidence closer to 1-2 per 10,000. These numbers vary significantly over different geographical areas. For example, studies in the Akita region of Japan record HHT incidence at 1 in 5000-8000 which is comparable to the numbers reported from Fyn County Denmark, and also to some reported studies from American and European populations (2, 3). In contrast, incidence has been reported to be as high as 1:2351 in the Haut Jura region of France (4, 5), and 1 in 1331 in the Afro-Caribbean population of the Netherlands Antilles (6, 7). The mode of disease transmission is autosomal dominant, affecting both genders equally. Penetrance has been estimated at 97% to 100% and is age dependent with clinical manifestations appearing progressively over the patients lifetime. Nearly 100% of patients will display the disease phenotype prior to 40 years of age (8, 9). In addition, 20% of the patients have a negative family history illustrating the contribution of spontaneous mutations, variability in individual clinical manifestations, and insufficient screening of the family members (1).

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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