Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

No abstract

No abstract

Dynamic computed tomographic (CT) findings of arteriovenous malformation (AVM) of the pancreas include strong enhancement or conglomeration of small hypervascular spots in the pancreas and early contrast filling of the portal vein during the arterial phase. We describe a case with pancreatic AVM in which we identified enlarged arterial feeders and draining veins as supportive findings of the diagnosis and ulceration into the pancreatic duct as a possible cause of gastrointestinal bleeding at contrast-enhanced CT.

No abstract

No abstract

Background Hypertrophic cardiomyopathy (HCM) is thought to be associated with microvascular dysfunction. Adenosine stress-perfusion cardiovascular magnetic resonance imaging (CMR) is a sensitive method for assessing microvascular perfusion abnormalities. We evaluated the prevalence and clinical characteristics of HCM patients with adenosine-induced perfusion defects on CMR. Methods Among 189 consecutive patients with HCM who underwent adenosine-stress perfusion CMR, 115 patients who had clinical, echocardiography, 24-h Holter monitoring and treadmill exercise test data were analyzed. We calculated myocardial perfusion ratio index from the intensity-over-time curve to quantify perfusion defects. The presence and extent of the stress-induced perfusion defect were compared with clinical characteristics, presence and extent of late gadolinium enhancement (LGE), left ventricular (LV) mass index and volume, presence of non-sustained ventricular tachycardia (NSVT) and results of treadmill exercise test. Results The mean age of enrolled patients was 51.8 ± 11.3 years. Most patients were asymptomatic except 25 subjects presented with New York Heart Association Class II dyspnea and 16 patients with atypical non-exertional chest discomfort. LGE was present in 103 (89.6%) subjects. Adenosine stress-induced perfusion defects were present in 48 (42%) subjects. None of the perfusion defects corresponded with a single or multiple coronary artery territories, showing a multiple patchy pattern in 24 (50.0%), a concentric subendocardial pattern in 20 subjects (41.7%), and as a single blot-like defect in the remaining 4 (8.3%). A perfusion defect was associated with NSVT, LV apical aneurysm, higher LV mass index, and higher LGE volume on univariate analysis. Multivariate analysis revealed female gender (P = 0.008), presence of apical aneurysm and NSVT (P = 0.036 and 0.047, respectively), and LV mass index (P = 0.022) to be independently associated with adenosine stress-induced perfusion defects. Conclusions In patients with HCM, adenosine-stress perfusion defects on CMR are present in more than 40% of subjects. This perfusion defect is associated with NSVT, higher LV mass index, and apical aneurysms. The prognostic value of this finding needs further elucidation.

Aims We investigated the prognostic role of left ventricular global longitudinal strain (LV-GLS) and its incremental value to established risk models for predicting sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). Methods and results LV-GLS was measured with vendor-independent software at a core laboratory in a cohort of 835 patients with HCM (aged 56.3 ± 12.2 years) followed-up for a median of 6.4 years. The primary endpoint was SCD events, including appropriate defibrillator therapy, within 5 years after the initial evaluation. The secondary endpoint was a composite of SCD events, heart failure admission, heart transplantation, and all-cause mortality. Twenty (2.4%) and 85 (10.2%) patients experienced the primary and secondary endpoints, respectively. Lower absolute LV-GLS quartiles, especially those worse than the median (−15.0%), were associated with progressively higher SCD event rates (P = 0.004). LV-GLS was associated with an increased risk for the primary endpoint, independent of the LV ejection fraction, apical aneurysm, and 2014 European Society of Cardiology (ESC) risk score [adjusted hazard ratio (aHR) 1.14, 95% confidence interval (CI) 1.02–1.28] or 2011 American College of Cardiology/American Heart Association (ACC/AHA) risk factors (aHR 1.18, 95% CI 1.05–1.32). LV-GLS was also associated with a higher risk for the composite secondary endpoint (aHR 1.06, 95% CI 1.01–1.12). The addition of LV-GLS enhanced the performance of the ESC risk score (C-statistic 0.756 vs. 0.842, P = 0.007) and the 2011 ACC/AHA risk factor strategy (C-statistic 0.743 vs. 0.814, P = 0.007) for predicting SCD. Conclusion LV-GLS is an important prognosticator in patients with HCM and provides additional information to established risk stratification strategies for predicting SCD.