Beyond Epistaxis: Cascade Screening and Presymptomatic Treatment of Hereditary Hemorrhagic Telangiectasia

Background Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder that may present with recurrent epistaxis, mucocutaneous telangiectasias, or visceral arteriovenous malformations (AVMs), 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, following a brief history of headache and vomiting. She had a background of infrequent nosebleeds and a family history of recurrent epistaxis in multiple maternal relatives. Genetic testing in the mother diagnosed HHT (heterozygous for NM_001114753(ENG):c.1134G>A (p.Ala378=) , an established pathogenic variant). Cascade testing for her two surviving children was done. The fifteen-year-old boy tested positive and was found on subsequent screening to have intracranial vascular malformations which were treated pre-symptomatically with gamma knife surgery. Another son tested negative. Conclusion This case emphasizes the prompt recognition of HHT 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 can prevent catastrophic outcomes such as intracranial hemorrhage. This case emphasizes the need for heightened awareness of HHT in pediatric practice and supports the value of integrating genetic cascade testing and organ-specific screening in at-risk children, even before symptoms appear.