Kjeldsen A D, Møller T R, Brusgaard K, Vase P, Andersen P E
Department of Otorhinolaryngology, Odense University Hospital, Odense, Denmark.
J Intern Med. 2005 Oct;258(4):349-55. doi: 10.1111/j.1365-2796.2005.01555.x.
Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically heterogeneous disorder involving at least two loci; HHT 1 mapping to chromosome 9 q 34.1 (ENG) and HHT 2 mapping to chromosome 12 q 31 (ALK-1).
To evaluate and describe the diversity of clinical manifestations in a Danish population of HHT patients with known HHT 1 or HHT 2 subtype.
Prospective clinical examination with genetic evaluation and follow-up.
Investigation centre was Odense University Hospital. All HHT patients in the County of Fyn were included.
HHT family members were invited to a clinical examination including registration of HHT manifestations, screening for PAVM and neurological evaluation. Blood tests were performed for analysis of disease-causing mutation, and clinical manifestations in the HHT subtypes were compared. The survival of the patients was studied in the follow-up period.
Included in the study were 73 HHT patients representing 18 families. In 14 of the families we identified a disease-causing mutation. Thirty-nine patients (from 10 families) had HHT1 and 16 HHT patients from four families had HHT2.
Amongst patients with HHT1 genotype the prevalence of PAVM was higher than amongst HHT patients with HHT2 genotype. HHT1 patients had experienced more severe GI bleeding than HHT2 patients. There was no significant difference in severity of epistaxis or age at debut. Finally the mortality over a 90-month observation period was not significantly increased.
遗传性出血性毛细血管扩张症（HHT）是一种常染色体显性遗传病，其临床表现多种多样，包括鼻出血、胃肠道出血、肺动静脉畸形（PAVM）和神经症状。HHT是一种基因异质性疾病，至少涉及两个基因座；HHT 1定位于9号染色体长臂34.1区（ENG），HHT 2定位于12号染色体长臂31区（ALK-1）。
评估并描述丹麦已知HHT 1或HHT 2亚型的HHT患者群体的临床表现多样性。
进行基因评估和随访的前瞻性临床检查。
调查中心为欧登塞大学医院。纳入了菲英岛郡的所有HHT患者。
邀请HHT家庭成员参加临床检查，包括记录HHT表现、筛查PAVM和进行神经学评估。进行血液检测以分析致病突变，并比较HHT各亚型的临床表现。在随访期研究患者的生存率。
本研究纳入了代表18个家庭的73例HHT患者。在其中14个家庭中我们鉴定出致病突变。39例患者（来自10个家庭）为HHT1型，16例来自4个家庭的HHT患者为HHT2型。
在HHT1基因型患者中，PAVM的患病率高于HHT2基因型的HHT患者。HHT1患者经历的胃肠道出血比HHT2患者更严重。鼻出血的严重程度或首发年龄无显著差异。最后，在90个月的观察期内死亡率没有显著增加。
