Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia.
BACKGROUND
Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically heterogeneous disorder involving at least two loci; HHT 1 mapping to chromosome 9 q 34.1 (ENG) and HHT 2 mapping to chromosome 12 q 31 (ALK-1).


OBJECTIVE
To evaluate and describe the diversity of clinical manifestations in a Danish population of HHT patients with known HHT 1 or HHT 2 subtype.


METHODS
Prospective clinical examination with genetic evaluation and follow-up.


METHODS
Investigation centre was Odense University Hospital. All HHT patients in the County of Fyn were included.


METHODS
HHT family members were invited to a clinical examination including registration of HHT manifestations, screening for PAVM and neurological evaluation. Blood tests were performed for analysis of disease-causing mutation, and clinical manifestations in the HHT subtypes were compared. The survival of the patients was studied in the follow-up period.


RESULTS
Included in the study were 73 HHT patients representing 18 families. In 14 of the families we identified a disease-causing mutation. Thirty-nine patients (from 10 families) had HHT1 and 16 HHT patients from four families had HHT2.


CONCLUSIONS
Amongst patients with HHT1 genotype the prevalence of PAVM was higher than amongst HHT patients with HHT2 genotype. HHT1 patients had experienced more severe GI bleeding than HHT2 patients. There was no significant difference in severity of epistaxis or age at debut. Finally the mortality over a 90-month observation period was not significantly increased.
Kjeldsen
A D
AD
Department of Otorhinolaryngology, Odense University Hospital, Odense, Denmark. jakjeldsen@dadlnet.dk
Møller
T R
TR
Brusgaard
K
K
Vase
P
P
Andersen
P E
PE
D030201:Activin Receptors, Type I / Q000235:genetics*; D030301:Activin Receptors, Type II; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001165:Arteriovenous Malformations / Q000150:complications / Q000235:genetics / Q000401:mortality; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D000071063:Endoglin; D004844:Epistaxis / Q000150:complications / Q000235:genetics / Q000401:mortality; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000150:complications / Q000235:genetics / Q000401:mortality; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D015995:Prevalence; D011651:Pulmonary Artery; D011667:Pulmonary Veins; D011956:Receptors, Cell Surface; D015996:Survival Rate; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000150:complications / Q000235:genetics* / Q000401:mortality; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; C425364:ACVRL1 protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II