RESUMO
In this retrospective single-center study, we evaluated whether/how pathogenic/likely pathogenic variants of three hereditary hemorrhagic telangiectasia (HHT)-associated genes (ENG, ACVRL1, and SMAD4) are associated with specific clinical presentations of HHT. We also characterized the morphological features of pulmonary arteriovenous malformations (AVMs) in patients with these variants. Pathogenic or likely pathogenic variants were detected in 64 patients. Using nonparametric statistical tests, we compared the type and prevalence of specific HHT diagnostic features associated with these three variants. Pathogenic variants in these genes resulted in gene-specific HHT clinical presentations. Epistaxis was present in 93%, 94%, and 100% of patients with ENG, ACVRL1, and SMAD4 variants, respectively (p = 0.79). Pulmonary AVMs were more common in patients with the ENG variant (p = 0.034) compared with other subgroups. ACVRL1 variant was associated with the lowest frequency of pulmonary AVMs (p = 0.034) but the highest frequency of hepatic AVMs (p = 0.015). Patients with the ACVRL1 variant did not have significantly more pancreatic AVMs compared with the other groups (p = 0.72). ENG, ACVRL1, and SMAD4 pathogenic or likely pathogenic variants are associated with gene-specific HHT presentations, which is consistent with results from other HHT centers.
Assuntos
Receptores de Activinas Tipo II/genética , Fístula Arteriovenosa/genética , Endoglina/genética , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/genética , Adulto , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/patologia , Feminino , Predisposição Genética para Doença , Fator 2 de Diferenciação de Crescimento/genética , Humanos , Masculino , Mutação/genética , Artéria Pulmonar/patologia , Veias Pulmonares/patologia , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/patologia , Proteína p120 Ativadora de GTPase/genéticaRESUMO
OBJECTIVES/HYPOTHESIS: Hereditary hemorrhagic telangiectasia (HHT) is a disease of abnormal angiogenesis, causing epistaxis in over 96% of patients. The Epistaxis Severity Score (ESS) was developed as a standardized measurement of nasal symptoms among HHT patients. The minimal important difference (MID) of a disease index estimates the smallest change that a patient and clinician would identify as important. This study aims to establish the MID of the ESS in a diverse population of HHT patients. STUDY DESIGN: Retrospective cross-sectional study in patients with a diagnosis of HHT using Curacao criteria or genetic testing. METHODS: The ESS questionnaire and Medical Outcomes Study 36-Item Short Form (SF-36) were administered to participants recruited through the HHT Foundation Web site. Demographics and relevant medical histories were collected from all participants. An anchor-based method using a change of 5 in the Physical Component Summary (PCS) of the SF-36 and a distributional method were used to estimate the MID. RESULTS: A total of 604 subjects were recruited between April and August 2008. All participants reported epistaxis. An increasing ESS in the study cohort showed a significant negative correlation to the PCS (r = -0.43, P < 0.001). The MID was determined to be 0.41 via the anchor-based approach and 1.01 via the distribution-based approach, giving a mean MID of 0.71. CONCLUSION: Using both the anchor-based and distribution-based approaches, the estimated MID for the ESS in HHT is 0.71. Further implications include key metrics to help guide treatment responses in clinical care and essential information to calculate power and sample size for future clinical trials. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1029-1032, 2016.