Hereditary Haemorrhagic Telangiectasia in Denmark. Surveillance - manifestations of the disease
Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is an autosomal dominantly inherited disease, with high penetrance, extremely variable age-dependent expression and very heterogeneous phenotypic presentations. Around 800 Danes are affected. HHT is characterized by the presence of multiple telangiectatic lesions in the mucosa and the skin and development of arteriovenous lesions. The various sorts of vascular malformations may cause ?life-threatening symptoms, which may be difficult to treat. Evaluation of the patients are centralised at the HHT-center at Odense University Hospital (OUH).
As HHT is a rare disease with very variable manifestations, there is a great risk of selection bias, as only the most severely affected patients are referred for treatment on a regular basis. The mildly affected cases are often only seen at the HHT center once, at the time of diagnosis.
However prognosis of disease is dependent on knowledge of both severe and mild manifestations. This may be difficult for doctors only seeing a few severe cases from time to time. Furthermore, some of the clinical manifestation may have a very abrupt and severe debut, as for example cerebral abscess and cerebral thrombosis. It is therefore important, when research projects are performed, to include patients with all levels off severity and follow the patients for a long period of time. This is why a database including all HHT patients seen at least once at the HHT center OUH is important.
This enables us to perform surveillance of development of disease severity, for example according to age of debut and according to genetic mutation. We will also be able to gather information on effect of different screening and treatment strategies.
Description of the cohort
The cohort is primarily bases on HHT patients from the former county of Fyn. All HHT patients and their 1 degree relatives (from the County of Fyn) were identified and evaluated for HHT in 1995. The HHT center OUH was established in 1998 and since that time, patients from all other parts of Denmark have been referred for evaluation of HHT manifestations, clinical and genetic diagnosis. Therefore, the HHT database is almost complete, concerning the County of Fyn. From other parts of Denmark there may be some referral bias. Presently we anticipate that around 50% of the Danish HHT patients are included in the database, but as all HHT patients in Denmark are referred for evaluation at the HHT-center, the number is growing. The HHT patients are followed during their life time.
Data and biological material
The data collected are clinical data concerning the various HHT manifestations and results of mutation analysis. Further information concerning familial relationships is collected.
Collaborating researchers and departments
Department of Oto-rhino-laryngologi, Odense University Hospital
- Professor and Consultant Anette Kjeldsen, PhD
OPEN Odense Patient data Explorative Network, Odense University Hospital
- Professor and Consultant Epidemiologist Anders Green, MD, DMSc, PhD
Publications associated with the project
National mutation study among Danish patients with Hereditary Haemorrhagic Telangiectasia. / Tørring PM, Brusgaard K, Ousager LB, Andersen PE, Kjeldsen AD. Clin Genet. 2013 Sep 3. [Epub ahead of print]
Cerebral abscesses among Danish patients with hereditary haemorrhagic telangiectasia. / Kjeldsen AD, Tørring PM, Nissen H, Andersen PE. Acta Neurol Scand. 2014 Mar ;129(3):192-7. 2013 Aug 20. [Epub ahead of print]
Clinical symptoms according to geno-type amongst patients with hereditary haemorrhagic telangiectasia. Kjeldsen AD, Moller TR, Brusgaard K, Vase P, Andersen PE. J Intern Med. 2005 Oct;258(4):349-55.
Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia. / Brusgaard K, Kjeldsen AD, Poulsen L, Moss H, Vase P, Rasmussen K, Kruse TA, Horder M. Clin Genet. 2004 Dec;66(6):556-61
Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT). / Kjeldsen AD, Oxhoj H, Andersen PE, Green A, Vase P. J Intern Med. 2000 Sep;248(3):255-62.
Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia. / Kjeldsen AD, Kjeldsen J. Am J Gastroenterol. 2000 Feb;95(2):415-8.
Hereditary haemorrhagic telangiectasia: a population-based study of prevalence and mortality in Danish patients.
/ Kjeldsen AD, Vase P, Green A. J Intern Med. 1999 Jan;245(1):31-9.
Pulmonary arteriovenous malformations: a radiological and clinical investigation of 136 patients with long-term follow-up. Andersen PE, Tørring PM, Duvnjak S, Gerke O, Nissen H, Kjeldsen AD. Clin Radiol. 2018 Nov;73(11):951-957. doi: 10.1016/j.crad.2018.07.096. Epub 2018 Aug 4.
Prevalence of hereditary hemorrhagic telangiectasia in patients operated for cerebral abscess: a retrospective cohort analysis. Larsen L, Marker CR, Kjeldsen AD, Poulsen FR. Eur J Clin Microbiol Infect Dis. 2017 Oct;36(10):1975-1980. doi: 10.1007/s10096-017-3023-7. Epub 2017 Jun 3.
JP-HHT phenotype in Danish patients with SMAD4 mutations. Jelsig AM, Tørring PM, Kjeldsen AD, Qvist N, Bojesen A, Jensen UB, Andersen MK, Gerdes AM, Brusgaard K, Ousager LB. Clin Genet. 2016 Jul;90(1):55-62. doi: 10.1111/cge.12693. Epub 2015 Dec 21.
20-year follow-up study of Danish HHT patients-survival and causes of death. Kjeldsen A, Aagaard KS, Tørring PM, Möller S, Green A. Orphanet J Rare Dis. 2016 Nov 22;11(1):157.