Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterised by vascular dysplasia complicated by visceral arteriovenous malformations (AVMs). To date, the diagnostic yield of screening procedures for pulmonary and cerebral AVMs in children with definite or potential HHT is not well defined. The aim of the present study was to prospectively evaluate the diagnostic yield of a screening protocol for pulmonary and cerebral AVMs in children with either a definite or potential HHT diagnosis.All children referred for evaluation for HHT between 1996 and 2008 were included in the present analysis. Screening tests for AVMs included chest computed tomography and brain magnetic resonance imaging.61 children with a definite clinical and/or genetic diagnosis of HHT were asymptomatic for visceral AVMs at their first baseline assessment (mean¡SD age 8.7¡4.7 yrs; range 0-17.0 yrs). Of these, 15 (25%) had pulmonary and/or cerebral AVMs diagnosed on initial screening tests. Pulmonary AVMs predominated in paediatric HHT patients (14 out of 15 patients) and were found in eight children aged ,10 yrs. 55 children had a potential HHT diagnosis as they fulfilled only one or two HHT clinical diagnostic criteria and did not have a confirmatory genetic diagnosis (age 10.9¡4.8 yrs; range 0-17.9 yrs). None of these children had pulmonary or cerebral AVMs on initial screening tests.The present data suggest that children with a definite HHT diagnosis have a high frequency of pulmonary AVMs even when clinically asymptomatic. In contrast, no AVMs were observed in children not fulfilling HHT diagnostic criteria. Genetic testing appears to be useful in defining an at-risk group for pulmonary AVMs in childhood.

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Background Approximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have associated morbidity. The modified Rankin Scale (mRS) may provide an approach to identifying HHT-brain VM patients with poor outcomes, and their predictors. We aimed to measure the relationship between mRS score and brain VM, brain VM number, as well as other aspects of HHT, at enrollment and during prospective follow-up. Methods 1637 HHT patients (342 with brain VMs) were recruited from 14 HHT centres of the Brain Vascular Malformation Consortium since 2010 and followed prospectively (mean = 3.4 years). We tested whether the presence of brain VM, other HHT organ involvement, and HHT mutation genotype were associated with worse mRS scores at baseline and during follow-up, using linear mixed models, adjusting for age, sex, and year of visit. Results Presence of brain VMs was not associated with worse mRS score at baseline and there was no significant worsening of mRS with prospective follow-up in these patients; 92% had baseline mRS of 0–2. HHT-related gastrointestinal (GI) bleeding was associated with worse mRS scores at baseline (0.37, 95% CI 0.26–0.47, p < 0.001), as were history of anemia (0.35, 95% CI 0.27–0.43, p < 0.001) and liver VMs (0.19, 95% CI 0.09–0.30, p < 0.001). Presence of pulmonary arteriovenous malformations (AVMs) was not associated with worse mRS scores at baseline. mRS score was not associated with either HHT genotype (Endoglin vs ACVRL1). Only GI bleeding was associated with a significantly worsening mRS during prospective follow-up (0.64, 95% CI 0.21–1.08, p = 0.004). Conclusion Most HHT-brain VM patients had good functional capacity (mRS scores 0–2) at baseline that did not change significantly over 3.4 mean years of follow-up, suggesting that mRS may not be useful for predicting or measuring outcomes in these patients. However, HHT patients with GI bleeding, anemia history or liver VMs had worse mRS scores, suggesting significant impact of these manifestations on functional capacity. Our study demonstrates the insensitivity of the mRS as an outcomes measure in HHT brain VM patients and reinforces the continued need to develop outcomes measures, and their predictors, in this group.