Clin Exp Otorhinolaryngol.  2021 Nov;14(4):399-406. 10.21053/ceo.2020.02124.

Genetic Variants and Clinical Phenotypes in Korean Patients With Hereditary Hemorrhagic Telangiectasia

• Kim BG
• Jung Jh
• Kim MJ
• Moon EH
• Oh JH
• Park JW
• Cha HE
• Kim JH
• Kim YJ
• Chung JW
• Hahm KB
• Jin HR
• Jang YJ
• Kim SW
• Chung SK
• Kim DW
• Lee YJ
• Kim ST

• KMID: 2522431
• DOI: http://doi.org/10.21053/ceo.2020.02124

Abstract

Objectives
. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients.
Methods
. Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated.
Results
. In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms.
Conclusion
. Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Keyword

Hereditary Hemorrhagic Telangiectasia; ACVRL1; ENG; Genetic Screening

Figure

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  Fig. 1. Seventy-two family members of patients with definite or probable hereditary hemorrhagic telangiectasia (HHT) were genetically screened for pathogenic variants in known HHT genes (ENG and ACVRL1). Clinical and genetic analyses were performed of the genetic variant-positive and negative patients.

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  Fig. 2. Telangiectasia lesions (circles) were detected on the nasal mucosa (A, B), tongue (C), and lip (D) in an hereditary hemorrhagic telangiectasia (HHT) patient (family 16). Pulmonary arteriovenous malformation lesions (arrows) in lung computed tomography images in the same HHT patient (E, F).

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