Giordano P, Nigro A, Lenato G M, Guanti G, Suppressa P, Lastella P, DE Mattia D, Sabbà C
Pediatrics Unit, Medicine and Public Health University of Bari, Bari, Italy.
J Thromb Haemost. 2006 Jun;4(6):1237-45. doi: 10.1111/j.1538-7836.2006.01934.x.
Rendu-Osler-Weber syndrome, or hereditary hemorrhagic telangiectasia (HHT), is an autosomal dominant vascular disorder. The syndrome is characterized by telangiectases and arteriovenous malformations (AVMs) affecting skin, mucosae and internal organs. AVMs often remain clinically silent until provoking sudden serious complications, responsible for important morbidity and mortality which can occur both in adulthood and in children. The incidence of AVMs in HHT pediatric populations is unknown.
To describe the screening protocol performed in the first genotypically confirmed HHT pediatric population and to estimate the incidence of occult brain, lung and liver AVMs and the different disease phenotypes.
Molecular analysis was performed on 35 children, both symptomatic and asymptomatic, who were family members of probands with a previously identified mutation. Clinical-instrumental examination was performed on the mutation positive cases. Nasal telangiectases were investigated by anterior rhinoscopy. Contrast echocardiography and high resolution thoracic multislice computed tomography (CT) were performed to detect pulmonary arteriovenous malformations (PAVMs), and echo-color Doppler, and abdominal CT to detect hepatic arteriovenous malformations (HAVMs). Brain magnetic resonance imaging was utilized to detect cerebral angiopathic involvement.
Molecular analysis demonstrated the mutation-carrier status in 22/35 children. Nineteen children, 12 of whom had epistaxis, positive to molecular testing underwent clinical evaluation. Nasal teleangiectases were found in 68%, mucocutaneous telangiectases (fingers, lips and oral cavity) in 79%, PAVMs in 53%, HAVMs in 47% and cerebral anteriovenous malformations and/or cerebral ischemic changes secondary to PAVMs in 12%.
We evidenced a high incidence of HHT children with occult visceral lesions suggesting that a diagnostic screening may be indicated to appropriately treat brain and lung malformations.
遗传性出血性毛细血管扩张症（HHT），又称朗杜-奥斯勒-韦伯综合征，是一种常染色体显性血管疾病。该综合征的特征是毛细血管扩张和动静脉畸形（AVM），累及皮肤、黏膜和内脏器官。AVM在临床上通常无症状，直到引发突然的严重并发症，导致成人和儿童出现重要的发病率和死亡率。HHT儿童群体中AVM的发病率尚不清楚。
描述在首个基因确诊的HHT儿童群体中执行的筛查方案，并估计隐匿性脑、肺和肝AVM的发病率以及不同的疾病表型。
对35名有症状和无症状的儿童进行分子分析，这些儿童是先前已确定突变的先证者的家庭成员。对突变阳性病例进行临床仪器检查。通过前鼻镜检查鼻毛细血管扩张。进行对比超声心动图和高分辨率胸部多层计算机断层扫描（CT）以检测肺动静脉畸形（PAVM），进行超声彩色多普勒检查和腹部CT以检测肝动静脉畸形（HAVM）。利用脑磁共振成像检测脑血管病变。
分子分析显示22/35名儿童为突变携带者。19名分子检测呈阳性的儿童接受了临床评估，其中12名有鼻出血症状。68%的儿童发现有鼻毛细血管扩张，79%的儿童有皮肤黏膜毛细血管扩张（手指、嘴唇和口腔），53%的儿童有PAVM，47%的儿童有HAVM，12%的儿童有脑动静脉畸形和/或继发于PAVM的脑缺血改变。
我们证明HHT儿童隐匿性内脏病变的发病率很高，这表明可能需要进行诊断性筛查以适当治疗脑和肺畸形。
