ORIGINAL ARTICLE

Visceral manifestations in hereditary haemorrhagic telangiectasia type 2

S A Abdalla¹, U W Geisthoff², D Bonneau³, H Plauchu⁴, J McDonald⁵, S Kennedy⁶, M E Faughnan⁷, M Letarte¹

¹ Cancer Research Program, The Hospital for Sick Children, and Department of Immunology, University of Toronto, Toronto, Canada
² Univ-HNO-Klinik, Kirrberger Strasse, D-66421 Homburg/Saar, Germany
³ Service de Génétique Médicale, Centre Hospitalier Universitaire d’Angers, 49100 Angers, France
⁴ Réseau Français Rendu Osler (INSERM-AFM-MR), Université Claude Bernard Lyon 1, Unité de Génétique Clinique (HCL), Hôpital Hôtel Dieu, 69288 Lyon, France
⁵ HHT Clinic, Department of Radiology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA
⁶ Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada
⁷ Division of Respiratory Medicine, Department of Medicine, St Michael’s Hospital, University of Toronto, Toronto, Canada

Correspondence to:
Correspondence to:
Dr S A Abdalla, Cancer Research Program, The Hospital for Sick Children, 555 University Avenue, Toronto M5G 1X8, Canada;
mablab{at}sickkids.ca

Hereditary haemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterised by epistaxis, telangiectases, and visceral manifestations. The two known disease types, HHT1 and HHT2, are caused by mutations in the endoglin (ENG) and ALK-1 genes, respectively. A higher frequency of pulmonary arteriovenous malformations (AVMs) has been reported for HHT1 while HHT2 is thought to be associated with a lower penetrance and milder disease manifestations. In this study, we present 10 families with an ALK-1 genotype. Visceral manifestations were detected in 24 (26%) of the 93 HHT2 patients from nine of the families and included gastrointestinal bleeding (14%), intrahepatic shunts (6%), and AVMs in the lung (4%) and brain (3%). Gastrointestinal bleeding, the most frequent visceral manifestation, was reported in six of the 10 families, mostly in patients over the age of 50. These patients also had frequent epistaxis and suffered from anaemia, often requiring blood transfusions. The identification of ALK-1 mutations in subjects with a suspected diagnosis and without clinical signs of HHT argue in favour of a molecular diagnosis. We also analysed the data published on 44 families with HHT2 and conclude that visceral manifestations occur in 26 of these families and affect 30% of HHT2 patients. This is considered an underestimate given incomplete and variable screening for lung, brain, and/or liver involvement in different clinical centres. These findings, however, stress the need for an early diagnosis of HHT that can be useful for the early control of associated visceral involvement.

Keywords: vascular disorder; TGF-ß receptors; arteriovenous; visceral manifestations

Abbreviations: HHT, hereditary haemorrhagic telangiectasia; CT, computed tomography; CE, contrast echocardiography; MRI, magnetic resonance imaging; MRA, magnetic resonance angiography; AVM, arteriovenous malformation

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