Seven cases of hereditary haemorrhagic telangiectasia-like hepatic vascular abnormalities associated with <i>EPHB4</i> pathogenic variants.

Abstract

<i>EPHB4</i> loss of function is associated with type 2 capillary malformation-arteriovenous malformation syndrome, an autosomal dominant vascular disorder. The phenotype partially overlaps with hereditary haemorrhagic telangiectasia (HHT) due to epistaxis, telangiectases and cerebral arteriovenous malformations, but a similar liver involvement has never been described. Members of the French HHT network reported their cases of <i>EPHB4</i> mutation identified after an initial suspicion of HHT. Clinical, radiological and genetic characteristics were analysed. Among 21 patients with <i>EPHB4</i>, 15 had a liver imaging, including 7 with HHT-like abnormalities (2 female patients and 5 male patients, ages 43-69 years). Atypical epistaxis and telangiectases were noted in two cases each. They were significantly older than the eight patients with normal imaging (median: 51 vs 20 years, p<0.0006).The main hepatic artery was dilated in all the cases (diameter: 8-11 mm). Six patients had hepatic telangiectases. All kind of shunts were described (arteriosystemic: five patients, arterioportal: two patients, portosystemic: three patients). The overall liver appearance was considered as typical of HHT in six cases.Six <i>EPHB4</i> variants were classified as pathogenic and one as likely pathogenic, with no specific hot spot. <i>EPHB4</i> loss-of-function variants can be associated with HHT-like hepatic abnormalities and should be tested for atypical HHT presentations.