Beyond epistaxis: cascade screening and presymptomatic treatment of hereditary hemorrhagic telangiectasia

鼻出血之外:遗传性出血性毛细血管扩张症的级联筛查和症状前治疗

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Abstract

BACKGROUND: Hereditary Hemorrhagic Telangiectasia is an autosomal dominant vascular disorder with clinical features of recurrent epistaxis, mucocutaneous telangiectasias, or visceral arteriovenous malformations, yet its early signs may be overlooked in children. CASE PRESENTATION: We report a family in which a fifteen-year-old boy and his mother presented for genetic evaluation of recurrent epistaxis, after his previously well seven-year-old sister demised suddenly from likely spontaneous atraumatic intracranial hemorrhage (diagnosed clinically without confirmatory post-mortem imaging), following a brief history of headache and vomiting. The mother had a background of infrequent nosebleeds and a family history of recurrent epistaxis in multiple maternal relatives. Genetic testing identified heterozygosity for NM_001114753.3(ENG): c.1134G > A (p.Ala378=), a ClinVar classified pathogenic variant, confirming the diagnosis of hereditary hemorrhagic telangiectasia. Cascade testing for her two surviving children was done. Her fifteen-year-old son tested positive and was found on subsequent screening to have intracranial vascular malformations which were treated presymptomatically with gamma knife surgery. Her other son tested negative. CONCLUSION: This case emphasizes the importance of prompt recognition of hereditary hemorrhagic telangiectasia in children presenting with recurrent epistaxis and highlights the need for thorough family history. Pediatricians play a crucial role in early diagnosis and referral for genetic testing with subsequent surveillance imaging. Early identification may possibly reduce the risk of unfavorable outcomes such as intracranial hemorrhage. This case emphasizes the need for heightened awareness of hereditary hemorrhagic telangiectasia in pediatric practice and supports the value of integrating genetic cascade testing and organ-specific screening in at-risk children, even before symptoms appear.

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