Sadick Haneen, Sadick Maliha, Götte Karl, Naim Ramin, Riedel Frank, Bran Gregor, Hörmann Karl
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany,
Wien Klin Wochenschr. 2006 Mar;118(3-4):72-80. doi: 10.1007/s00508-006-0561-x.
Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal dominant disorder of the fibrovascular tissue. It is characterized by the classic triad of (muco-)cutaneous telangiectases, arteriovenous malformations with recurrent epistaxis and hemorrhages, and inheritance. A wide variety of clinical manifestations in HHT have been described. In more than 90% of the patients, nosebleeds are the first predominant symptom, therefore ENT physicians often play a key role as far as diagnosis and management of the disease are concerned. In spite of recent diagnostic and therapeutic progress, a cure for this often burdening and handicapping disease is still not available. Apart from affecting the nose, arteriovenous malformations (AVMs) may also affect the skin, lungs, brain, liver and gastrointestinal tract. The two known genes that are implicated in HHT are endoglin (ENG) located on chromosome 9q33-q34 and activin-receptor-like kinase (ALK1) located on chromosome 12q13. Mutations of ENG are observed in HHT type 1 with an incidence up to 40% for pulmonary AVMs, whereas mutations of ALK1 are observed in HHT type 2 with an incidence of only 14% for pulmonary AVMs, which clinically distinguishes these two types of mutation. The emphasis of this paper is mainly on the clinical manifestation, molecular genetics and diagnosis of HHT, taking account of current literature on HHT in order to better understand the complexity of the disease. Recent therapeutic options in the treatment of HHT have been omitted from this paper as they are subject of a following paper. HHT is more common than previously thought and shows a broad range of different clinical organ manifestations that can be sources of substantial morbidity and mortality, making HHT a continuing challenge for many sub-specialties where interdisciplinary diagnostic screening is mandatory in the management of the disease.
遗传性出血性毛细血管扩张症（HHT），也被称为伦杜 - 奥斯勒 - 韦伯病，是一种常染色体显性纤维血管组织疾病。其特征为典型的三联征：（黏膜）皮肤毛细血管扩张、伴有反复鼻出血和出血的动静脉畸形以及遗传。HHT 已被描述有多种临床表现。超过 90%的患者鼻出血是首要主要症状，因此就该疾病的诊断和管理而言，耳鼻喉科医生通常起着关键作用。尽管最近在诊断和治疗方面取得了进展，但对于这种常常带来负担和致残的疾病仍无治愈方法。除了影响鼻子外，动静脉畸形（AVM）还可能影响皮肤、肺、脑、肝脏和胃肠道。已知与 HHT 相关的两个基因是位于 9 号染色体 q33 - q34 区域的内皮素（ENG）和位于 12 号染色体 q13 区域的激活素受体样激酶（ALK1）。在 1 型 HHT 中观察到 ENG 突变，肺动静脉畸形的发生率高达 40%，而在 2 型 HHT 中观察到 ALK1 突变，肺动静脉畸形的发生率仅为 14%，这在临床上区分了这两种类型的突变。本文重点主要在于 HHT 的临床表现、分子遗传学和诊断，参考了当前关于 HHT 的文献，以便更好地理解该疾病的复杂性。本文未提及 HHT 近期的治疗选择，因为它们是后续一篇论文的主题。HHT 比之前认为的更为常见，并且表现出广泛的不同临床器官表现，这些表现可能是严重发病和死亡的根源，使得 HHT 对许多亚专业来说仍然是一个持续的挑战，在该疾病的管理中跨学科诊断筛查是必不可少的。
