致家族性鼻出血的HHT患者误诊误治情况及基因诊断研究

发布时间：2018-03-29 22:36

  本文选题：鼻出血　切入点：毛细血管扩张　出处：《中国人民解放军医学院》2016年硕士论文

【摘要】：鼻出血是耳鼻咽喉头颈外科常见急症,而家族性、自发性、反复大量鼻出血是遗传性出血性毛细血管扩张症(Hereditary hemorrhagic telangiectasia, HHT)最常见的临床表现。鼻出血严重程度随年龄增大而逐渐加重,患者常因严重贫血而需要反复输血才能维持生命。HHT是一种以血管发育畸形为特征的常染色体显性遗传病,患病率约为1/5000,无性别差异,但种族差异明显,约90%的患者未被正确诊断。HHT主要表现为反复发生的自发性鼻出血、胃肠道出血、皮肤黏膜毛细血管扩张以及内脏动静脉畸形。以往该病的诊断主要依靠临床诊断,而目前基因诊断为该病早期诊断和确诊提供了可能性。由于HHT临床少见,涉及耳鼻喉科、血液科、皮肤科、消化科、神经内科、呼吸内科、妇产科等多个科室,多数接诊医生对该病认识不足,极易造成漏诊和误诊。目的：分析HHT误诊误治情况,提高诊治水平。应用基因检测方法,提高HHT客观诊断水平,并早期确诊HHT家系中无症状儿童及成年人。方法：收集自2014年3月至2016年3月就诊于解放军总医院耳鼻咽喉头颈外科门诊的HHT先证者,回顾性分析其临床表现、既往诊治经过、误诊误治情况,同时对HHT先证者及其亲属进行基因筛查,早期诊断或排除该病,并对其提供遗传咨询。结果：2014年3月至2016年3月我们课题组共确诊11例HHT先证者,其中男性6例,女性5例,平均年龄52.72岁(28-68岁),均主诉反复自发性鼻出血前来我院就诊,81.8%(9/11)为中重度鼻出血(ESS评分4分)；平均误诊时间26.18年(7-50年),多误诊为单纯鼻出血和贫血而行对症处理,02、03家系先证者误诊为造血系统疾病而行骨髓穿刺术,02家系先证者误诊为子宫内膜异位症而行子宫切除术,06家系先证者误诊为鼻甲血管瘤行鼻内镜下血管瘤切除术；2例需反复输血治疗,1例已行2次肺动静脉瘘栓塞术,欲行肺叶切除术,08家系兄弟姐妹5人均为HHT患者,2人罹患贫血性心脏病,其中1人已去世,其余HHT先证者目前无严重并发症发生10个HHT家系共筛查出致病突变基因8例,08家系拒绝行基因检测,10家系尚未检测到致病基因突变。临床确诊为HHT的患者突变基因检出率为88.9%(8/9),其中ENG基因突变2例(25%), ACVRL1基因突变6例(75%), SMAD4基因突变0例(0%), ENG/ACVRL1比值为0.3；检测到的ACVRL1基因突变类型主要为错义突变(5例,83%),ENG基因突变均为无义突变(2例,100%);新发现致病突变3例,2例为ACVRL1基因突变,1例为ENG基因突变,均影响蛋白质功能。通过基因检测,确诊HHT家系无症状儿童或成年人5例,排除2例。结论：HHT是一涉及多器官、多系统的全身性疾病,但患者多因鼻出血而就诊于耳鼻咽喉头颈外科,因此首诊医师针对反复自发性鼻出血患者应注意询问家族史并行皮肤黏膜体征检查,以早期明确诊断,从而进行多脏器筛查以早期治疗,预防致命性并发症的发生。同时,基因检测是针对该病最客观的诊断方法,对于临床确诊、临床疑诊患者,HHT家系中无症状未成年人均应行基因检测,以明确诊断或排除HHT。
[Abstract]:Epistaxis is a common emergency of Otolaryngology Head and neck surgery, and familial, spontaneous, is hereditary hemorrhagic telangiectasia with repeated hemorrhage (Hereditary hemorrhagic telangiectasia, a large number of nasal HHT) the most common clinical manifestations. Nasal bleeding severity gradually increased with the increase of age, patients often due to severe anemia and require repeated transfusion to maintain life is a kind of.HHT with vascular malformation characterized by autosomal dominant disease prevalence rate is about 1/5000, but no difference in sex, racial differences, about 90% of the patients were not correct diagnosis of.HHT mainly manifested as recurrent spontaneous bleeding of nasal mucosa, gastrointestinal bleeding, skin telangiectasia and visceral arteriovenous the deformity. The diagnosis mainly depends on clinical diagnosis, and the gene diagnosis for early diagnosis and diagnosis of the disease. The clinical HHT offers the possibility of less See, to the Department of ENT, Department of Hematology, Department of Dermatology, Department of Gastroenterology, respiratory medicine, neurology, obstetrics and gynecology department and other departments, the majority of doctors lack of awareness of the disease, easily lead to misdiagnosis. Objective: to analyze HHT misdiagnosis, improve the level of diagnosis and treatment. Method are applied to detect gene, improve HHT objective diagnosis the level of asymptomatic children and adults, and early diagnosis of HHT pedigree. Methods: collected from March 2014 to March 2016 in PLA General Hospital of Otolaryngology Head and neck surgery outpatient HHT probands, retrospective analysis of the clinical manifestations, previous diagnosis and treatment after misdiagnosis, while HHT probands and their relatives genetic screening, early diagnosis or exclusion of the disease, and provide genetic counseling for them. Results: from March 2014 to March 2016 our group a total of 11 cases were diagnosed HHT probands, there were 6 males and 5 females, the average age of 52.7 2宀，

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