Neurointervention.  2019 Sep;14(2):91-98. 10.5469/neuroint.2019.00150.

Current Status of Clinical Diagnosis and Genetic Analysis of Hereditary Hemorrhagic Telangiectasia in South Korea: Multicenter Case Series and a Systematic Review

• Kim D
• Seo EJ
• Song YS
• Suh CH
• Kim JW
• Kim DJ
• Suh DC

• KMID: 2458488
• DOI: http://doi.org/10.5469/neuroint.2019.00150

Abstract

PURPOSE
Hereditary hemorrhagic telangiectasia (HHT), a rare genetic vascular disorder, has been rarely reported in South Korea. We investigated the current prevalence and presenting patterns of genetically confirmed HHT in South Korea.
MATERIALS AND METHODS
We defined HHT patients as those with proven mutations on known HHT-related genes (ENG, ACVRL1, SMAD4, and GDF2) or those fulfilling 3 or 4 of the Curaçao criteria. A computerized systematic search was performed in PubMed and KoreaMed using the following search term: ("hereditary hemorrhagic telangiectasia" AND "Korea") OR ("Osler-Weber-Rendu" AND "Korea"). We also collected government health insurance data. HHT genetic testing results were collected from three tertiary hospitals in which the genetic tests were performed. We integrated patient data by analyzing each case to obtain the prevalence and presenting pattern of HHT in South Korea.
RESULTS
We extracted 90 cases from 52 relevant articles from PubMed and KoreaMed. An additional 22 cases were identified from the three Korean tertiary hospitals after excluding seven cases that overlapped with those in the published articles. Finally, 112 HHT patients were identified (41 males and 71 females, aged 4-82 years [mean±standard deviation, 45.3±20.6 years]). The prevalence of HHT in South Korea is about 1 in 500,000, with an almost equal prevalence among men and women. Forty-nine patients underwent genetic testing, of whom 28 had HHT1 (ENG mutation) and 19 had HHT2 (ACVRL1 mutation); the other two patients were negative for ENG, ACVRL1, and SMAD4 mutations.
CONCLUSION
The prevalence of HHT is underestimated in Korea. The rate of phenotypic presentation seems to be similar to that found worldwide. Korean health insurance coverage is limited to representative genetic analysis to detect ENG and ACVRL1 mutations. Further genetic analyses to detect HHT3, HHT4, and other forms of HHT should be implemented.

Keyword

Telangiectasia, Hereditary hemorrhagic; Arteriovenous malformations; Arteriovenous fistula; Hemorrhage; Epistaxis

MeSH Terms

Arteriovenous Fistula
Arteriovenous Malformations
Diagnosis*
Epistaxis
Female
Genetic Testing
Hemorrhage
Humans
Insurance, Health
Korea*
Male
Prevalence
Telangiectasia, Hereditary Hemorrhagic*
Tertiary Care Centers

Figure

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  Fig. 1. Flow diagram of article search and case retrieval.

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  Fig. 2. A 60-year-old female with clinically confirmed human hereditary telangiectasia presented with repeated epistaxis that required embolization (A). Note mucocutaneous telangiectasias in hands (B) and tongue (C).

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  Fig. 3. A family tree of a 7-yearold boy (proband, arrow) who presented with multiple brain arteriovenous fistulae. Positive sign (+) indicates the presence of the ENG c.808C>T (p.Gln270Ter) hetero variant; negative sign (-) indicates its absence. DM, diabetes mellitus; AVF, arteriovenous fistula; AVM, arteriovenous malformation; ICH, intracranial hemorrhage.

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