Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with unknown pathophysiology that is characterised by arteriovenous lesions and recurrent haemorrhage in virtually every organ. Linkage of HHT to markers on chromosome 9q has recently been reported. In this study we report confirmation of this localisation in three unrelated families of Dutch origin. A fourth unrelated HHT family, in which considerably fewer pulmonary arteriovenous malformations (PAVM) were present, yielded evidence for non-linkage to this region. We conclude that HHT is a genetically heterogeneous disorder and our results indicate that the presence of PAVM may be more common in patients with a chromosome 9 linked form of HHT than in patients with the non-linked form. (J Med Genet 1994;31:933-936) Hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Rendu-Weber disease, is a rare disorder characterised by arteriovenous communications which may develop in virtually every organ.' These lesions mostly appear as easily bleeding telangiectases in the skin and mucosa, but may also give rise to larger arteriovenous malformations, for example, in the lung or in the brain. Clinical manifestations depend on the location and size of the vascular anomaly: epistaxis is frequently present, intestinal bleeding can occur, dyspnoea and cyanosis can arise from arteriovenous malformations in the pulmonary circulation, and bleeding of cerebral lesions may cause serious complications.'2 Since therapy can prevent a number of complications, case finding is useful.The first patient with HHT was described by Babington3 in 1865; Rendu4 suggested a hereditary trait as the cause for familial epistaxis and telangiectasia, which was confirmed by Osler5 and Weber.6 The prevalence of HHT ranges between 1 to 2 per 100 000 and 1 per 10 000 with almost complete penetrance by the age of 40 years.79 The mode of inheritance is autosomal dominant. The disease occurs in all races, and is equally frequent in both sexes.710One homozygous child has been described who died of bleeding and hypoxaemia soon after birth." Several earlier linkage studies led to inconclusive results owing to the low informativeness of the markers used."1-'5In order to perform a systematic genome and family members participating in a family screening study (manuscript in preparation). All were investigated for the presence of mucocutaneous telangiectasia, including inspection of the nasal mucosa. All affected persons were screened for pulmonary arteriovenous malformations (PAVM) by chest radiography and measurement of arterial oxygenation. Intravenous digital subtraction angiography (iv-DSA) of the pulmonary circulation was performed in patients with abnormalities on either chest radiography or in arterial oxygenation. Also, iv-DSA of the cerebral circulation was done in all affected persons to screen for cerebral arteriovenous malformations (CAVM).
(<10%).In order to make multipoint analysis manageable, the five most relevant markers were recoded to no more t...
