Clinical analysis of seven cases of pulmonary hypertension in children with gene mutation
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摘要: 收集2014年1月-2018年3月就诊我院，右心导管确诊肺动脉高压，基因检测阳性的患儿共7例，分析其临床特点及预后转归。不明原因儿童肺动脉高压基因阳性发病率为32%，其中BMPR2突变3例，ACVRL1突变2例，FLNA突变1例，NOTCH3突变1例，KMT2D突变1例。男女比例为1∶6，初诊年龄8个月~15岁，随访时间9~31个月。所有患儿均有活动耐量下降，随访中1例因大咯血死亡，2例因心力衰竭死亡，2例出现心力衰竭加重在调整治疗后病情平稳，2例病情平稳。Abstract: A total of 7 children with pulmonary hypertension diagnosed by right cardiac catheterization and positive gene test were collected from January 2014 to March 2018. Their clinical characteristics and prognosis were analyzed. Incidence of gene mutation was 32%. Of which three were BMPR2 mutation, two were ACVRL1 mutation, one was FLNA mutation, one was NOTCH3 mutation, and one was KMT2D mutation. The ratio of male to female was 1∶6. The first diagnosis age was 8 months to 15 years old, and the follow-up time was 9 to 31 months. All the children had decreased activity tolerance. In the follow-up, 1 case died of massive hemoptysis, 2 cases died of heart failure, 2 cases developed heart failure aggravation, and 2 cases were stable.
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Key words:
- children /
- pulmonary arterial hypertension /
- gene mutation /
- gene detection
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表 1 7例基因突变PAH患儿一般情况
Table 1. General data
例序 性别 年龄 基因及突变类型 NT-proBNP/(pg·mL-1) 症状 NYHA心功能 合并CHD 靶向药物 随访时间/月 随访结果 1 女 9岁 BMPR2、错义突变 710 活动耐量下降 Ⅱ 无 波生坦他达拉非 31 病情反复 2 男 15岁 ACVRL1、错义突变 1192 活动耐量下降、咯血 Ⅲ 无 波生坦西地拉非 9 死亡 3 女 8个月 FLNA、剪切突变 15 000 活动耐量下降、反复呼吸道感染 Ⅳ PDA(2 mm)ASD(5 mm) 波生坦 20 死亡 4 女 3岁 BMPR2、错义突变ACVRL1、错义突变 8000 活动耐量下降 Ⅳ 无 波生坦 12 死亡 5 女 9岁 NOTCH3、错义突变 430 活动耐量下降 Ⅱ PFO 波生坦他达拉非 16 平稳 6 女 3.5岁 KMT2D、移码突变 1200 活动耐量下降 Ⅳ ASD(5 mm)VSD(3 mm) 波生坦西地拉非瑞莫杜林 21 病情反复 7 女 10岁 BMPR2、移码突变 410 活动耐量下降 Ⅱ 无 波生坦他达拉非 10 平稳 注：CHD为先天性心脏病。 
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表 2 7例基因突变PAH患儿心脏超声数据
Table 2. Echocardiographic data
mm 例序 右房内径 左房内径 右室内径 左室内径 肺动脉内径 主动脉内径 1 32 22 35 32 29 19 2 80 31 70 35 39 23 3 36 19 35 25 24 16 4 23 19 29 25 24 17 5 29 22 34 30 21 17 6 24 19 29 24 23 17 7 30 23 35 30 21 18
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表 3 7例基因突变PAH患儿右心导管数据
Table 3. Data of right heart catheterization
例序 MPAP/mmHg DAP/mmHg PVR/(WOOD·U) PVRI/(WOODU·m-2) CO/(L·min-1) CI/(L·min-2) 1 60 62 11.4 15.1 3.77 2.86 2 71 73 18.1 35 6.31 3.26 3 第一次
第二次2467 7056 1741.9 5.419 1.131.85 3.64.07 4 69 66 55.7 24.8 1.37 1.46 5 90 95 43.1 41.4 6.61 6.88 6 68 67 - - - - 7 46 75 - - - - 注：DAP为降主动脉压；PVRI为肺血管阻力指数；CO为心输出量。
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表 4 7例基因突变PAH患儿随访数据
Table 4. Follow-up data
随访项目 例1 例2 例3 例4 例5 例6 例7 NT-proBNP/(pg·mL-1) 基线 710 1192 15 000 8 000 430 1 200 410 随访 41.2 ＞35 000 ＞35 000 ＞35 000 - 443.7 151.3 NYHA心功能 基线 Ⅱ Ⅲ Ⅳ Ⅳ Ⅱ Ⅳ Ⅱ 随访 Ⅱ Ⅳ Ⅳ Ⅳ Ⅱ Ⅲ Ⅱ RV/LV 基线 1.1 2 1.4 1.2 1.1 1.2 1.2 随访 1.1 2.2 1.6 1.4 0.8 1.1 1.3 结局 存活 死亡 死亡 死亡 存活 存活 存活 注：RV/LV为右室舒张末内径/左室舒张末内径。
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