title: Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers.
abstract: BACKGROUND
  Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs), particularly in the brain (CAVMs), lungs (PAVMs), liver (HAVMs) and gastrointestinal tract (GI). The identification of a mutated ENG (HHT1) or ALK-1 (HHT2) gene now enables a genotype-phenotype correlation.
  
  
  OBJECTIVE
  To determine the incidence of visceral localizations and evaluate phenotypic differences between ENG and ALK1 mutation carriers.
  
  
  METHODS
  A total of 135 consecutive adult patients were subjected to mutational screening in ENG and ALK1 genes and instrumental tests to detect AVMs, such as chest-abdomen multislice computed tomography (MDCT), brain magnetic resonance imaging and magnetic resonance angiography (MRI/MRA), upper endoscopy, were offered to all patients, independent of presence of clinical symptoms. The 122 patients with identified mutations were enrolled in the study and genotype-phenotype correlations were established.
  
  
  RESULTS
  PAVMs and CAVMs were significantly more frequent in HHT1 (75% vs. 44%, P < 0.0005; 20% vs. 0%, P < 0.002, respectively) and HAVMs in HHT2 (60% vs. 84%, P < 0.01). No age difference was found for PAVMs whereas HAVMs were significantly higher in older patients in both HHT1 and HHT2. Neurological manifestations secondary to CAVMs/PAVMs were found only in HHT1 patients, whereas severe liver involvement was detected only in HHT2. Respiratory symptoms were mainly detected in HHT1.
  
  
  CONCLUSIONS
  Our study evidences a higher visceral involvement in HHT1 and HHT2 compared with previous reports. HHT1 is more frequently associated with congenital AVM malformations, such as CAVMs and PAVMs whereas HHT2 predominantly involves the liver. The ENG gene should be first targeted for mutational screening in the presence of large PAVM in patients < 45 years.
authors: Department of Internal Medicine and Public Health, University of Bari, Bari, Italy. c.sabba@dimimp.uniba.it
authors: C
authors: C
authors: Sabbà
authors: G
authors: G
authors: Pasculli
authors: G M
authors: GM
authors: Lenato
authors: P
authors: P
authors: Suppressa
authors: P
authors: P
authors: Lastella
authors: M
authors: M
authors: Memeo
authors: F
authors: F
authors: Dicuonzo
authors: G
authors: G
authors: Guant
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D001165:Arteriovenous Malformations / Q000235:genetics / Q000473:pathology; D000071063:Endoglin; D004844:Epistaxis / Q000235:genetics; D005260:Female; D041981:Gastrointestinal Tract / Q000098:blood supply; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics; D008099:Liver / Q000098:blood supply; D008168:Lung / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009928:Organ Specificity; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics*; 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