畑 忠善

UNLABELLED: Most cases of pulmonary arteriovenous malformation (PAVM) are associated with hereditary hemorrhagic telangiectasia (HHT). HHT is typically caused by loss-of-function gene mutations in the genes ENG, ACVRL1, or SMAD4, all participating in transforming growth factor β (TGF-β) family signaling pathways. We describe the case of an 11-year-old Japanese girl with PAVM, with no known family history of HHT or similar disease. She was found to carry a novel nonsense variant in SMAD9 (SMAD9-p. T267*), which we speculate contributed to her disease, because SMAD9 also participates in TGF-β family signaling pathways. SMAD9 mutations have been linked with pulmonary arterial hypertension (PAH), and, hence, mutations in SMAD9-as for ENG, ACVRL1, and SMAD4-may predispose to both PAH and HHT(-characteristic) disease features. The PAVM in our patient spread diffusely inside the lower lobe of the left lung, and coil embolization was considered difficult. Therefore, after feasibility assessment by performing a balloon occlusion test during cardiac catheterization, left lower lobectomy was performed. The patient's dyspnea recovered well postoperatively, and two years later an increase in left lung volume was observed and disease symptoms had not recurred. Thus, if PAVM spreads diffusely in a certain lung area, surgical treatment can be a viable option. LEARNING OBJECTIVE: SMAD9 gene mutations have been linked to pulmonary arterial hypertension (PAH). However, their associations with hereditary hemorrhagic telangiectasia (HHT) or pulmonary arteriovenous malformation (PAVM), which usually is HHT-associated, have not been reported previously. Our PAVM patient carrying a SMAD9 variant suggests that mutations in this gene, like in others participating in TGF-β family signaling pathways (like ENG, ACVRL1, and SMAD4), predispose to both PAH and HHT(-characteristic) disease features. Diffuse PAVM confined to a lung area may be treated by lobectomy.

OBJECTIVES: The Gunma score is used to predict the severity of Kawasaki disease (KD), including coronary artery aneurysm (CAA) as a cardiac complication, in Japan. Additionally, the characteristic ratio of ventricular repolarization (T-peak to T-end interval to QT interval [Tp-e/QT]) on a surface electrocardiogram reflects myocardial inflammation. This study aimed to determine whether the Tp-e/QT can be used to predict CAA in children with KD. METHODS: We analyzed chest surface electrocardiograms of 112 children with KD before receiving intravenous immunoglobulin therapy using available software (QTD; Fukuda Denshi, Tokyo, Japan). RESULTS: The Tp-e/QT (lead V5) was positively correlated with the Gunma score (r=0.352, p<0.001). The Tp-e/QT was larger in patients with CAA (residual CAA at 1 month after onset) than in those without CAA (0.314±0.026 versus 0.253±0.044, p=0.003). A receiver operating characteristic curve analysis was performed to assess whether the Gunma score and Tp-e/QT could predict subsequent CAA. The area under the curve of the Gunma score was 0.719 with the cutoff set at 5 points. The area under the curve of the Tp-e/QT was 0.892 with a cutoff value of 0.299. The fit of the prediction models to the observed probability was tested by the Hosmer-Lemeshow test with calibration plots using Locally weighted scatterplot smoothing (LOESS) fit. The Gunma score (p=0.95) and Tp-e/QT (p=0.95) showed a good fit. CONCLUSIONS: The Tp-e/QT is a useful biomarker in predicting coronary aneurysm complications in KD.