Screening for pulmonary and cerebral arteriovenous malformations in children with hereditary haemorrhagic telangiectasia

Abstract

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.

Pulmonary Arteriovenous Malformations and Cerebral Abscess Recurrence in a Child With Hereditary Hemorrhagic Telangiectasia

“…24 Misdiagnosis in our patient likely took place due to the paucity of nosebleeds and mucocutaneous telangiectases, which are the best known HHT clinical signs, although their utility is limited in children. [3][4][5] Yet, both BA episodes might have been prevented in this patient, as HHT had initially been diagnosed in his maternal grandmother's sister. Our case further stresses the very high relevance to extend awareness of HHT to as many familiars as possible, whenever a patient is diagnosed with this disease, even in kindreds without previous history of visceral involvement, as BA is a serious complication that can also affect HHT children.…”

“…3 As the disease does not often reach full clinical expression in youngsters, the knowledge of the diseasecausing mutation in a given family permits to assess a firm HHT diagnosis also in asymptomatic or paucisymptomatic children who do not meet clinical criteria. [3][4][5] In pediatric age, pulmonary AVMs (PAVMs) occur in 30% to 45% of HHT patients, 25% to 40% of those will develop PAVMrelated symptoms. [4][5][6] Manifestations of PAVMs include hypoxemia features (dyspnea, cyanosis, and polycythemia), hemoptysis, as well as risk of developing neurological complications, such as stroke or cerebral abscess, by paradoxical embolization.…”

“…[3][4][5] In pediatric age, pulmonary AVMs (PAVMs) occur in 30% to 45% of HHT patients, 25% to 40% of those will develop PAVMrelated symptoms. [4][5][6] Manifestations of PAVMs include hypoxemia features (dyspnea, cyanosis, and polycythemia), hemoptysis, as well as risk of developing neurological complications, such as stroke or cerebral abscess, by paradoxical embolization. 7,8 Neurological complications can be associated with respiratory symptoms or, in some cases, occur as the first clinical manifestation of otherwise asymptomatic PAVMs.…”

Idiopathic pulmonary arteriovenous malformations: clinical and imaging characteristics

“…HHT is often unrecognised in children and young adults, as the clinical expression of HHT is agerelated [35]. For example, ,50% of children with HHT have epistaxis or telangiectasia [36] but ,90% of adults .50 yrs of age have recurrent epistaxis [35,37]. However, given that the mean age in our group of ''possible'' patients is .50 yrs, none had a family history of HHT and all (six out of six) had negative genetic testing for ENG and ACVRL1 mutation, it is unlikely that many of these patients have HHT.…”

Hereditary hemorrhagic teleangiectasia: the topical problems of diagnostics and surgical treatment

“…Частота поражения внутренних органов также увеличивается с возрастом, достигая максимума к 70 годам [4,6,24]. Часто висцеральные АВМ, осо бенно легочные, увеличиваются в размерах и кли нически проявляются во время беременности, осо бенно во II и III триместрах [25].…”