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. 2020 Jul;22(7):1201-1205.
doi: 10.1038/s41436-020-0775-8. Epub 2020 Apr 17.

Curaçao diagnostic criteria for hereditary hemorrhagic telangiectasia is highly predictive of a pathogenic variant in ENG or ACVRL1 (HHT1 and HHT2)

Jamie McDonald  1   2 , Pinar Bayrak-Toydemir  3   4 , Desiree DeMille  4 , Whitney Wooderchak-Donahue  3   4 , Kevin Whitehead  5   6   7
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Free article

Curaçao diagnostic criteria for hereditary hemorrhagic telangiectasia is highly predictive of a pathogenic variant in ENG or ACVRL1 (HHT1 and HHT2)

Jamie McDonald et al. Genet Med. 2020 Jul.
Free article

Abstract

Purpose: Determine the variant detection rate for ENG, ACVRL1, and SMAD4 in individuals who meet consensus (Curaçao) criteria for the clinical diagnosis of hereditary hemorrhagic telangiectasia.

Methods: Review of HHT center database for individuals with three or more HHT diagnostic criteria, in whom molecular genetic analysis for ENG, ACVRL1, and SMAD4 had been performed.

Results: A variant known or suspected to be causal was detected in ENG in 67/152 (44.1%; 95% confidence interval [CI], 36.0-52.4%), ACVRL1 in 79/152 (52.0%; 95% CI, 43.7-60.1%), and SMAD4 in 2/152 (1.3%; 95% CI, 0.2-4.7%) family probands with definite HHT. Only 4/152 (2.6%; 95% CI, 0.7-6.6%) family probands did not have a variant in one of these genes.

Conclusion: Previous reports of the variant detection rate for ENG and ACVRL1 in HHT patients have come from laboratories, which receive samples from clinicians with a wide range of expertise in recognizing clinical manifestations of HHT. These studies suggest a significantly lower detection rate (~75-85%) than we have found in patients who meet strictly applied consensus criteria (96.1%). Analysis of SMAD4 adds an additional detection rate of 1.3%. HHT as defined by the Curaçao criteria is highly predictive of a causative variant in either ENG or ACVRL1.

Keywords: ACVRL1; Curaçao criteria; ENG; HHT.

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References

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