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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2016

Open Access 01-12-2016 | Research

Life expectancy of parents with Hereditary Haemorrhagic Telangiectasia

Authors: E. M. de Gussem, C. P. Edwards, A. E. Hosman, C. J. J. Westermann, R. J. Snijder, M. E. Faughnan, J. J. Mager

Published in: Orphanet Journal of Rare Diseases | Issue 1/2016

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Abstract

Background

Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disease associated with epistaxis, arteriovenous malformations and telangiectasias. Disease complications may result in premature death.

Method

We investigated life-expectancies of parents of HHT patients compared with their non-HHT partners using self- or telephone-administered questionnaires sent to their children. Patients were extracted from the databases of 2 participating HHT Centres: the Toronto HHT Database (Toronto, Canada) and the St. Antonius Hospital HHT Database (Nieuwegein, The Netherlands).

Results

Two hundred twenty five/407 (55 %) of respondents were included creating HHT- (n = 225) and control groups (n = 225) of equal size. Two hundred thirteen/225 (95 %) of the HHT group had not been screened for organ involvement of the disease prior to death. The life expectancy in parents with HHT was slightly lower compared to parents without (median age at death 73.3 years in patients versus 76.6 years in controls, p0.018). Parents with ACVRL 1 mutations had normal life expectancies, whereas parents with Endoglin mutations died 7.1 years earlier than controls (p = 0.024). Women with Endoglin mutations lived a median of 9.3 years shorter than those without (p = 0.04). Seven/123 (5 %) of deaths were HHT related with a median age at death of 61.5 years (IQ range 54.4–67.7 years).

Conclusion

Our study showed that the life expectancy of largely unscreened HHT patients was lower than people without HHT. Female patients with Endoglin mutations were most strikingly at risk of premature death from complications. These results emphasize the importance of referring patients with HHT for screening of organ involvement and timely intervention to prevent complications.
Literature
1.
Kjeldsen AD, Vase P, Green A. Hereditary haemorrhagic telangiectasia: a population-based study of prevalence and mortality in Danish patients. J Intern Med. 1999;245(1):31–9.CrossRefPubMed
2.
Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000;91(1):66–7.CrossRefPubMed
3.
McDonald MT, Papenberg KA, Ghosh S, Glatfelter AA, Biesecker BB, Helmbold EA, Markel DS, Zolotor A, McKinnon WC, Vanderstoep JL. A disease locus for hereditary haemorrhagic telangiectasia maps to chromosome 9q33-34. Nat Genet. 1994;6(2):197–204.CrossRefPubMed
4.
Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996;13(2):189–95.CrossRefPubMed
5.
Krings T, Kim H, Power S, Nelson J, Faughnan ME, Young WL, terBrugge KG, Brain Vascular Malformation Consortium HHT Investigator Group. Neurovascular manifestations in hereditary hemorrhagic telangiectasia: imaging features and genotype-phenotype correlations. AJNR Am J Neuroradiol. 2015;36(5):863–70.CrossRefPubMed
6.
Memeo M, Stabile Ianora AA, Scardapane A, Buonamico P, Sabba C, Angelelli G. Hepatic involvement in hereditary hemorrhagic telangiectasia: CT findings. Abdom Imaging. 2004;29(2):211–20.CrossRefPubMed
7.
Guttmacher AE, Marchuk DA, White Jr RI. Hereditary hemorrhagic telangiectasia. N Engl J Med. 1995;333(14):918–24.CrossRefPubMed
8.
Woodall MN, McGettigan M, Figueroa R, Gossage JR, Alleyne Jr CH. Cerebral vascular malformations in hereditary hemorrhagic telangiectasia. J Neurosurg. 2014;120(1):87–92.CrossRefPubMed
9.
Dupuis-Girod S, Giraud S, Decullier E, Lesca G, Cottin V, Faure F, Merrot O, Saurin JC, Cordier JF, Plauchu H. Hemorrhagic hereditary telangiectasia (Rendu-Osler disease) and infectious diseases: an underestimated association. Clin Infect Dis. 2007;44(6):841–5.CrossRefPubMed
10.
Mathis S, Dupuis-Girod S, Plauchu H, Giroud M, Barroso B, Ly KH, Ingrand P, Gilbert B, Godeneche G, Neau JP. Cerebral abscesses in hereditary haemorrhagic telangiectasia: a clinical and microbiological evaluation. Clin Neurol Neurosurg. 2012;114(3):235–40.CrossRefPubMed
11.
Garcia-Tsao G, Korzenik JR, Young L, Henderson KJ, Jain D, Byrd B, Pollak JS, White RI Jr. Liver disease in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2000;343(13):931–6.CrossRefPubMed
12.
Proctor DD, Henderson KJ, Dziura JD, Longacre AV, White Jr RI. Enteroscopic evaluation of the gastrointestinal tract in symptomatic patients with hereditary hemorrhagic telangiectasia. J Clin Gastroenterol. 2005;39(2):115–9.PubMed
13.
Sabba C, Pasculli G, Suppressa P, D'Ovidio F, Lenato GM, Resta F, Assennato G, Guanti G. Life expectancy in patients with hereditary haemorrhagic telangiectasia. QJM. 2006;99(5):327–34.CrossRefPubMed
14.
Donaldson JW, McKeever TM, Hall IP, Hubbard RB, Fogarty AW. Complications and mortality in hereditary hemorrhagic telangiectasia: A population-based study. Neurology. 2015;84(18):1886–93.CrossRefPubMedPubMedCentral
15.
Velthuis S, Vorselaars VM, van Gent MW, Westermann CJ, Snijder RJ, Mager JJ, Post MC. Role of transthoracic contrast echocardiography in the clinical diagnosis of hereditary hemorrhagic telangiectasia. Chest. 2013;144(6):1876–82.CrossRefPubMed
16.
Letteboer TG, Mager JJ, Snijder RJ, Koeleman BP, Lindhout D, Ploos van Amstel JK, Westermann CJ. Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia. J Med Genet. 2006;43(4):371–7.CrossRefPubMedPubMedCentral
17.
Kjeldsen AD, Moller TR, Brusgaard K, Vase P, Andersen PE. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia. J Intern Med. 2005;258(4):349–55.CrossRefPubMed
18.
Bayrak-Toydemir P, McDonald J, Markewitz B, Lewin S, Miller F, Chou LS, Gedge F, Tang W, Coon H, Mao R. Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet A. 2006;140(5):463–70.CrossRefPubMed
19.
van Gent MW, Post MC, Snijder RJ, Westermann CJ, Plokker HW, Mager JJ. Real prevalence of pulmonary right-to-left shunt according to genotype in patients with hereditary hemorrhagic telangiectasia: a transthoracic contrast echocardiography study. Chest. 2010;138(4):833–9.CrossRefPubMed
20.
Kjeldsen AD, Torring PM, Nissen H, Andersen PE. Cerebral abscesses among Danish patients with hereditary haemorrhagic telangiectasia. Acta Neurol Scand. 2014;129(3):192–7.CrossRefPubMed
21.
Shovlin CL, Jackson JE, Bamford KB, Jenkins IH, Benjamin AR, Ramadan H, Kulinskaya E. Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia. Thorax. 2008;63(3):259–66.CrossRefPubMed
22.
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, HHT Foundation International - Guidelines Working Group:. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet. 2011;48(2):73–87.CrossRefPubMed
23.
de Gussem EM, Lausman AY, Beder AJ, Edwards CP, Blanker MH, Terbrugge KG, Mager JJ, Faughnan ME. Outcomes of pregnancy in women with hereditary hemorrhagic telangiectasia. Obstet Gynecol. 2014;123(3):514–20.CrossRefPubMed
24.
Shovlin CL, Sodhi V, McCarthy A, Lasjaunias P, Jackson JE, Sheppard MN. Estimates of maternal risks of pregnancy for women with hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): suggested approach for obstetric services. BJOG. 2008;115(9):1108–15.CrossRefPubMed
25.
Yeomans ER, Gilstrap 3rd LC. Physiologic changes in pregnancy and their impact on critical care. Crit Care Med. 2005;33(10 Suppl):S256–8.CrossRefPubMed
26.
Lapinsky SE, Kruczynski K, Slutsky AS. Critical care in the pregnant patient. Am J Respir Crit Care Med. 1995;152(2):427–55.CrossRefPubMed
27.
Giordano P, Lenato GM, Suppressa P, Lastella P, Dicuonzo F, Chiumarulo L, Sangerardi M, Piccarreta P, Valerio R, Scardapane A, Marano G, Resta N, Quaranta N, Sabba C. Hereditary hemorrhagic telangiectasia: arteriovenous malformations in children. J Pediatr. 2013;163(1):179–86. e1-3.CrossRefPubMed
28.
Grosse SD, Boulet SL, Grant AM, Hulihan MM, Faughnan ME. The use of US health insurance data for surveillance of rare disorders: hereditary hemorrhagic telangiectasia. Genet Med. 2014;16(1):33–9.CrossRefPubMedPubMedCentral
29.
Latino GA, Brown D, Glazier RH, Weyman JT, Faughnan ME. Targeting under-diagnosis in hereditary hemorrhagic telangiectasia: a model approach for rare diseases? Orphanet J Rare Dis. 2014;9:115.CrossRefPubMedPubMedCentral
Metadata
Title
Life expectancy of parents with Hereditary Haemorrhagic Telangiectasia
Authors
E. M. de Gussem
C. P. Edwards
A. E. Hosman
C. J. J. Westermann
R. J. Snijder
M. E. Faughnan
J. J. Mager
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2016
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-016-0427-x

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