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The Stratified Population Screening of Hereditary Hemorrhagic Telangiectasia

  • Tamás MajorEmail author
  • Réka Gindele
  • Zsuzsanna Szabó
  • Zsuzsanna Kis
  • László Bora
  • Natália Jóni
  • Péter Bárdossy
  • Tamás Rácz
  • Zsuzsanna Bereczky
Short Communication
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Abstract

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular disease with a wordwide prevalence of 1:5000–1:10000. We introduce our algorithm for the stratified population screening of HHT. Probands are selected from the consecutive hospital database review for HHT (I7800) and recurrent epistaxis (R0400) and the review of patient records referred by family practicioners. A proportion of probands might be de novo diagnosed with HHT in the 10-year study period. The checkup of probands consists of physical examination, arteriovenous malformation exploration and and genetic testing (ACVRL1 and ENG sequence analysis). The family screening of HHT consists of physical examination and screening for the family-specific mutation of each at-risk individual, and furthermore, arteriovenous malformation exploration in individuals with suspected/definite HHT and/or carrying the mutation. Twenty-five definite HHT patients were explored: 7 of them by the I7800 review, 1 by the R0400 review, 3 were de novo diagnosed, and the remaining 14 were explored by the systematic family screening. Considering the 20 patients alive at the end of the study period and the unavailable 5 potential HHT patients and 12 at-risk family members, the HHT prevalence is estimated to be 1:6090–1:11267 in our study area, implying our algorithm’s effectivity in the stratified population screening of HHT.

Keywords

Hereditary hemorrhagic telangiectasia Prevalence Stratified screening ACVRL1 ENG Founder effect 

Notes

Acknowledgements

This study was funded by grants from the Hungarian National Research Fund (OTKA K116228) and by the Ministry of National Economy, Hungary (GINOP-2.3.2-15-2016-00039).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12253_2019_602_MOESM1_ESM.pptx (80 kb)
Online Resource 1 Pedigree charts of HHT families with ACVRL1 mutations. Probands are marked with arrows. Filled individuals are affected, either by carrying the mutation and/or having definite HHT. In the upper left index † = definite HHT, * = deceased or unavailable patient with epistaxis and/or telangiectases by hearsay. In the upper right index M = family-specific ACVRL1 mutation, w =  ACVRL1 wild type, u = patient unavailable for genetic screening. Individuals indicated with grey are living outside the study area (PPTX 80 kb)
12253_2019_602_MOESM2_ESM.pptx (105 kb)
Online Resource 2 Pedigree charts of HHT families with ENG mutations. Probands are marked with arrows. Filled individuals are affected, either by carrying the mutation and/or having definite HHT. In the upper left index † = definite HHT, * = deceased or unavailable patient with epistaxis and/or telangiectases by hearsay. In the upper right index M = family-specific ENG mutation, w = ENG wild type, u = patient unavailable for genetic screening. Individuals indicated with grey are living outside the study area (PPTX 105 kb)

References

  1. 1.
    Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H (2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-weber syndrome). Am J Med Genet 91:66–67CrossRefGoogle Scholar
  2. 2.
    Sharathkumar AA, Shapiro A (2008) Hereditary haemorrhagic telangiectasia. Haemophilia 14:1269–1280.  https://doi.org/10.1111/j.1365-2516.2008.01774.x CrossRefGoogle Scholar
  3. 3.
    University of Utah, Department of Pathology. HHT Mutation Database. http://arup.utah.edu/database/HHT/. Accessed December 3rd, 2018
  4. 4.
    Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, Proctor DD, Spears J, Brown DH, Buscarini E, Chesnutt MS, Cottin V, Ganguly A, Gossage JR, Guttmacher AE, Hyland RH, Kennedy SJ, Korzenik J, Mager JJ, Ozanne AP, Piccirillo JF, Picus D, Plauchu H, Porteous ME, Pyeritz RE, Ross DA, Sabba C, Swanson K, Terry P, Wallace MC, Westermann CJ, White RI, Young LH, Zarrabeitia R (2011) International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet 48:73–87.  https://doi.org/10.1136/jmg.2009.069013 CrossRefGoogle Scholar
  5. 5.
    Bayrak-Toydemir P, McDonald J, Markewitz B, Lewin S, Miller F, Chou LS, Gedge F, Tang W, Coon H, Mao R (2006) Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet 140:463–470.  https://doi.org/10.1002/ajmg.a.31101 CrossRefGoogle Scholar
  6. 6.
    Lesca G, Genin E, Blachier C, Olivieri C, Coulet F, Brunet G, Dupuis-Girod S, Buscarini E, Soubrier F, Calender A, Danesino C, Giraud S, Plauchu H (2008) Hereditary hemorrhagic telangiectasia: evidence for regional founder effects of ACVRL1 mutations in French and Italian patients. Eur J Hum Genet 16:742–749.  https://doi.org/10.1038/ejhg.2008.3 CrossRefGoogle Scholar
  7. 7.
    Brusgaard K, Kjeldsen AD, Poulsen L, Moss H, Vase P, Rasmussen K, Kruse TA, Hørder M (2004) Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet 66:556–561.  https://doi.org/10.1111/j.1399-0004.2004.00341.x CrossRefGoogle Scholar
  8. 8.
    Heimdal K, Dalhus B, Rodningen OK, Kroken M, Eiklid K, Dheyauldeen S, Røysland T, Andersen R, Kulseth MA (2015) Mutation analysis in Norwegian families with hereditary hemorrhagic telangiectasia: founder mutations in ACVRL1. Clin Genet 89:182–186.  https://doi.org/10.1111/cge.12612 CrossRefGoogle Scholar
  9. 9.
    Major T, Gindele R, Szabó Z, Alef T, Thiele B, Bora L, Kis Z, Bárdossy P, Rácz T, Havacs I, Bereczky Z (2016) Evidence for the founder effect of a novel ACVRL1 splice-site mutation in Hungarian hereditary hemorrhagic telangiectasia families. Clin Genet 90:466–467CrossRefGoogle Scholar
  10. 10.
    Torring PM, Brusgaard K, Ousager LB, Andersen PE, Kjeldsen AD (2014) National mutation study among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet 86:123–133.  https://doi.org/10.1111/cge.12269,  https://doi.org/10.1111/cge.12806

Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  • Tamás Major
    • 1
    • 2
    Email author
  • Réka Gindele
    • 3
  • Zsuzsanna Szabó
    • 3
  • Zsuzsanna Kis
    • 4
  • László Bora
    • 5
  • Natália Jóni
    • 6
  • Péter Bárdossy
    • 7
  • Tamás Rácz
    • 8
  • Zsuzsanna Bereczky
    • 3
  1. 1.Department of Otolaryngology and Head and Neck SurgeryB-A-Z County Central Hospital and University Teaching HospitalMiskolcHungary
  2. 2.Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház Fül-Orr-Gége és Fej-Nyak Sebészeti OsztályMiskolcHungary
  3. 3.Division of Clinical Laboratory Science, Department of Laboratory MedicineUniversity of DebrecenDebrecenHungary
  4. 4.Department of RadiologyFerenc Markhot County HospitalEgerHungary
  5. 5.Department of RadiologySzent Lázár County HospitalSalgótarjánHungary
  6. 6.Department of Internal MedicineFerenc Markhot County HospitalEgerHungary
  7. 7.Hungarian Heraldry and Genealogical SocietyBudapestHungary
  8. 8.Department of OtorhinolaryngologyFerenc Markhot County HospitalEgerHungary

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