G301(P) Diagnosing hereditary haemorrhagic telangiectasia in children: a service evaluation project

Background Hereditary haemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu syndrome, is an autosomal dominant disorder characterised by telangiectasia, epistaxis, and visceral arterio-venous malformations (AVMs). The value of Curacao diagnostic criteria may be limited in young children due to age-related penetrance of clinical features. Treatment of pulmonary and cerebral AVMs can improve long-term morbidity and mortality. Prophylactic antibiotics are recommended in specific circumstances. Aims To assess how many children receive a molecular diagnosis of HHT in our region. To review the utility of the Curacao criteria in children with molecularly confirmed HHT. Design A retrospective electronic case-note review of all patients assessed in a regional Clinical Genetics service between January 2012 and December 2017 was undertaken. Potential cases were identified by searching clinic letters for keywords (‘HHT’ or ‘telang*’) with matched review of molecular analysis. Results 23 children (age ≤16 years) were identified. Seven children (3 – 15 years) were referred with a clinical suspicion of HHT. Five of these children subsequently underwent genetic testing, with a molecular diagnosis of HHT confirmed in 2 (40%). The Curacao score for the 2 children with HHT was 3, compared to 2 in all those without a molecular diagnosis. Sixteen children (6 days – 16 years) were referred due to a parent having a molecular diagnosis of HHT. Of these, fifteen children underwent genetic testing, with the familial variant present in 8 (53%). The mean Curacao scores for children with and without a molecular diagnosis were 2.1 (1–3) and 1.3 (1–2) respectively (p=0.06). A further 13 children were identified to have a first degree relative with confirmed HHT. Half of these children would be expected to have a molecular diagnosis of HHT. Conclusion In total, 10 children had a confirmed molecular diagnosis of HHT. As others have reported, a low Curacao score is unreliable for excluding HHT in children. HHT should be considered in any child with AVMs, severe epistaxis or unexplained hypoxia. All children with a first degree relative with molecularly confirmed HHT should be offered genetic testing. Children with a molecular diagnosis or high clinical suspicion of HHT should be referred to a paediatrician with a special interest in HHT.