Department of Respiratory Medicine, Beijing Children's Hospital, National Center for Children's Health and Capital Medical University, Xicheng District, Beijing, People's Republic of China.
Department of Nuclear Medicine, Beijing Friendship Hospital and Capital Medical University, Xicheng District, Beijing, People's Republic of China; and.
Pediatrics. 2020 Aug;146(2). doi: 10.1542/peds.2019-1970. Epub 2020 Jul 15.
Hereditary hemorrhagic telangiectasia (HHT) can be clinically diagnosed, but children often lack characteristic features. We report a family with homozygous growth differentiation factor 2 ()-related HHT diagnosed by genetic testing. A boy aged 5 years and 2 months presented with isolated hypoxemia. He was the product of a consanguineous marriage; his parents were second cousins. Physical examination revealed cyanosis of nail beds and clubbed fingers. Pulse oxygen saturation was 84% to 89%. Lung function, contrast-enhanced lung computed tomography, and noncontrast echocardiography were normal. A pulmonary perfusion scan revealed radioactivity in the brain and bilateral kidney, suggesting the existence of a intrapulmonary shunt. Whole-exome sequencing revealed a homozygous variant [c.1060_1062delinsAG (p.Tyr354ArgfsTer15)] in , which was found to be inherited from his heterozygous parents. At the age of 8 years, he developed epistaxis, and an angiogram revealed diffuse pulmonary arteriovenous malformations. At the age of 9 years, he was treated with sirolimus, and his condition improved significantly. However, his now 7-year-old sister with the same homozygous variant currently has no symptoms. Physical examinations revealed 1 pinpoint-sized telangiectasia on the chest of his mother and a vascular lesion on the forehead of his sister. Additionally, the patient's father and great-uncle had a history of mild to moderate epistaxis. Mutation in is a rare cause of HHT. Ours is the first report of homozygous -related HHT; in addition, this variant has not been reported previously. In our report, we also confirm variable expressivity, even with the same pathogenic variant in -related HHT.
遗传性出血性毛细血管扩张症（HHT）可以临床诊断，但儿童常缺乏特征性表现。我们报告了一个通过基因检测诊断为纯合生长分化因子 2 （）相关 HHT 的家族。一名 5 岁零 2 个月的男孩以孤立性低氧血症就诊。他是近亲结婚的产物；其父母是表亲。体格检查显示指甲床和杵状指发绀。脉搏血氧饱和度为 84%至 89%。肺功能、对比增强肺部计算机断层扫描和非对比超声心动图正常。肺灌注扫描显示脑和双侧肾脏有放射性，提示存在肺内分流。外显子组测序显示 中存在纯合变异[c.1060_1062delinsAG（p.Tyr354ArgfsTer15）]，该变异来自其杂合父母。8 岁时，他出现鼻出血，血管造影显示弥漫性肺动静脉畸形。9 岁时，他接受了西罗莫司治疗，病情明显改善。然而，他现在 7 岁的同一位纯合变异的妹妹目前没有症状。体格检查发现他母亲的胸部有 1 个针尖大小的毛细血管扩张，他妹妹的额头上有血管病变。此外，患者的父亲和叔祖父有轻度至中度鼻出血的病史。 中的突变是 HHT 的罕见原因。我们的报告是首例纯合 -相关 HHT 的报告；此外，该变异尚未有报道。在我们的报告中，我们还证实了即使在 -相关 HHT 中存在相同的致病性变异，也存在可变表达性。
