Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

A D Kjeldsen, T R Møller, K Brusgaard, P Vase, P E Andersen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

DESIGN: Prospective clinical examination with genetic evaluation and follow-up.

SETTING: 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.

CONCLUSION: 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.

OriginalsprogEngelsk
TidsskriftJournal of Internal Medicine
Vol/bind258
Udgave nummer4
Sider (fra-til)349-355
ISSN0954-6820
DOI
StatusUdgivet - 2005

Fingeraftryk

Epistaxis
Lung
Chromosomes, Human, Pair 12
Mutation
Observation
Population

Citer dette

@article{07fd2790de9b11db9628000ea68e967b,
title = "Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia",
abstract = "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.DESIGN: Prospective clinical examination with genetic evaluation and follow-up.SETTING: 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.CONCLUSION: 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.",
keywords = "Activin Receptors, Type I, Activin Receptors, Type II, Adolescent, Adult, Aged, Antigens, CD, Arteriovenous Malformations, Chi-Square Distribution, DNA Mutational Analysis, Epistaxis, Female, Gastrointestinal Hemorrhage, Genotype, Humans, Male, Middle Aged, Point Mutation, Prevalence, Pulmonary Artery, Pulmonary Veins, Receptors, Cell Surface, Survival Rate, Telangiectasia, Hereditary Hemorrhagic, Vascular Cell Adhesion Molecule-1",
author = "Kjeldsen, {A D} and M{\o}ller, {T R} and K Brusgaard and P Vase and Andersen, {P E}",
year = "2005",
doi = "10.1111/j.1365-2796.2005.01555.x",
language = "English",
volume = "258",
pages = "349--355",
journal = "Journal of Internal Medicine",
issn = "0954-6820",
publisher = "Wiley-Blackwell",
number = "4",

}

Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia. / Kjeldsen, A D; Møller, T R; Brusgaard, K; Vase, P; Andersen, P E.

I: Journal of Internal Medicine, Bind 258, Nr. 4, 2005, s. 349-355.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

AU - Kjeldsen, A D

AU - Møller, T R

AU - Brusgaard, K

AU - Vase, P

AU - Andersen, P E

PY - 2005

Y1 - 2005

N2 - 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.DESIGN: Prospective clinical examination with genetic evaluation and follow-up.SETTING: 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.CONCLUSION: 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.

AB - 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.DESIGN: Prospective clinical examination with genetic evaluation and follow-up.SETTING: 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.CONCLUSION: 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.

KW - Activin Receptors, Type I

KW - Activin Receptors, Type II

KW - Adolescent

KW - Adult

KW - Aged

KW - Antigens, CD

KW - Arteriovenous Malformations

KW - Chi-Square Distribution

KW - DNA Mutational Analysis

KW - Epistaxis

KW - Female

KW - Gastrointestinal Hemorrhage

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Point Mutation

KW - Prevalence

KW - Pulmonary Artery

KW - Pulmonary Veins

KW - Receptors, Cell Surface

KW - Survival Rate

KW - Telangiectasia, Hereditary Hemorrhagic

KW - Vascular Cell Adhesion Molecule-1

U2 - 10.1111/j.1365-2796.2005.01555.x

DO - 10.1111/j.1365-2796.2005.01555.x

M3 - Journal article

C2 - 16164574

VL - 258

SP - 349

EP - 355

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0954-6820

IS - 4

ER -