title: Genotype-phenotype relationship for localization and age distribution of telangiectases in hereditary hemorrhagic telangiectasia.
abstract: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by arteriovenous malformations (AVMs) ranging from telangiectases to larger AVMs. Mutations in two genes cause HHT; ENG (HHT1) and ACVRL1 (HHT2). Although the hallmark for clinical diagnosis is the presence of telangiectases, there are few publications reporting the relative distribution and frequency of these features between HHT1 and HHT2. Here, the results of such analysis of telangiectases in 268 patients with HHT1 and 130 patients with HHT2 are described. Localization of the telangiectases is reported, and patients were clustered by age to estimate the site prevalence for different age categories. We show that telangiectases of the nasal mucosa are present at a higher prevalence and start to appear earlier in life than those of the oral mucosa or dermal sites in patients with either HHT1 or HHT2. Oral and nasal mucosal telangiectases are present earlier in life in patients with HHT1 compared to patients with HHT2, whereas dermal lesions are more frequent and appear earlier in life in patients with HHT2. In patients with either HHT1 or HHT2, the number of sites affected increases with age. In patients with HHT1, more women than men had skin telangiectases, particularly on the face. These results confirm that the frequency of AVMs differ between patients with HHT1 and HHT2, and that these differences can be detected on physical examination.
authors.affiliation: DBG-Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. t.g.w.letteboer@umcutrecht.nl
authors.forename: Tom G W
authors.initials: TG
authors.lastname: Letteboer
authors.forename: Hans-Jurgen
authors.initials: HJ
authors.lastname: Mager
authors.forename: Repke J
authors.initials: RJ
authors.lastname: Snijder
authors.forename: Dick
authors.initials: D
authors.lastname: Lindhout
authors.forename: Hans-Kristian
authors.initials: HK
authors.lastname: Ploos van Amstel
authors.forename: Pieter
authors.initials: P
authors.lastname: Zanen
authors.forename: Kees J J
authors.initials: KJ
authors.lastname: Westermann
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D000071063:Endoglin; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000098:blood supply / Q000473:pathology; D009297:Nasal Mucosa / Q000098:blood supply / Q000473:pathology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics; D012737:Sex Factors; D012867:Skin / Q000098:blood supply / Q000473:pathology; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000145:classification / Q000235:genetics* / Q000473:pathology*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II