Misdiagnosis And Genetic Features Of Hereditary Hemorrhagic Telangiectasia

Epistaxis is the emergency of Otolaryngology, and familial recurrent spontaneous epistaxis is the most common clinical manifestation of hereditary hemorrhagic telangiectasia (HHT). Epistaxis severity gradually increased with age and HHT patients often depends on repeated blood transfusion treatment because of anemia.HHT is an autosomal dominant genetic disease characterized by vascular malformations with the prevalence is about 1/5000 in the world, and 90% of which are undiagnosed. There are no gender differences in prevalence, but there are significant differences in race. The common manifestations of HHT are recurrent spontaneous epistaxis, gastrointestinal bleeding, capillary dilation on skin and mucosa and visceral arteriovenous malformations. Previously, the diagnosis of HHT mainly depended on the clinical diagnosis, and at present, the genetic diagnosis provides the possibility for the early diagnosis. HHT is rare in clinic and the attending doctors of different departments lack of understanding of the disease, this easily lead to misdiagnosis.Objective:To analyze the misdiagnosis and to improve the clinical diagnosis of HHT. To improve the early diagnosis of asymptomatic children and adults in HHT family by using gene detection that is the objective detection method.Methods:This study included 11 probands of HHT from March 2014 to March 2016 in PLA General Hospital of Otolaryngology Head and neck surgery clinic. Retrospective analysis of clinical manifestations, past diagnosis and treatment, misdiagnosis and wrong treatment of these 11 cases. And meanwhile provide a genetic screening for the HHT probands and its relatives, with the purpose of early diagnosis or exclusion of the disease, and providing genetic counseling to the HHT patients.Results:In 11 HHT patients,6 males and 5 females, the average age of 52.72 years (28-68 years); all complained of recurrent spontaneous epistaxis, the average ESS score of 5.57 (1.09-9.49).81.8% (9/11) for moderate and severe nasal bleeding (ESS>4); the average time of misdiagnosis was 26.18 years (7-50 years), mostly misdiagnosed as nasal bleeding and anemia,02 and 03 proband were misdiagnosed as hematopoietic system disease who underwent bone marrow puncture,02 proband were misdiagnosed as endometriosis underwent uterus resection, and 06 proband were misdiagnosed as turbinate hemangioma underwent endoscopic resection of hemangioma,2 cases required recurrent blood transfusion,1 case were underwent pulmonary arteriovenous fistula embolization and will be required to undergo lobectomia pulmonalis. All of 5 HHT patients in 08 family are siblings,2 people in which suffering from anemia heart disease,1 of them have died. There are no serious complications at the rest of HHT patients.Ten HHT families were screened for mutation in 8 cases, and mutation detection rate was 88.9% among patients with clinically diagnosed HHT. Of which 6 cases were ACVRL1 gene mutations (75%),2 cases were ENG gene mutation (25%),3 cases were new mutations with 2 were ACVRLlgene and 1 was ENG gene mutation. The mutation type was mainly missense mutation (5 cases,83%) in ACVRL1 and nonsense mutation (2 case,100%) in ENG. By using genetic screening,5 cases who without any sympotoms of HHT were diagnosed, and 2 cases were excluded.Conclusions:HHT is a systemic disease involves multiple organs and systems, but patients always see a doctor in otorhinolaryngology head and neck surgery with the epistaxis, so the first doctor should pay much attention to family history, skin and mucous membrane’s capillary dilation to make a definite early diagnosis, thus multiple organ screening to early treatment, and prevent fatal complications occurred.At the same time, genetic testing is the objective method for HHT, especially for the clinical suspected patient. To confirm the diagnosis or exclusion of HHT, gene detection should be taken on asymptoms minors in HHT families.