On the diagnosis of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic arteriopathy related to Notch3 mutations, is difficult to diagnosis. The goal of this study was to determine the value of clinical, immunohistochemical, and molecular techniques for the diagnosis of CADASIL. Clinical features and the immunohistochemical and molecular findings in 200 subjects with suspected CADASIL in whom 93 biopsies and 190 molecular studies are reported. Eighteen pathogenic mutations of the Notch3 gene, six of them previously unreported, were detected in 67 patients. The clinical features did not permit differentiation between CADASIL and CADASIL-like syndromes. The sensitivity and specificity of the skin biopsies was 97.7% and 56.5%, respectively, but increased to 100% and 81.5%, respectively, in cases with proven family history. In conclusion, a clinical diagnosis of CADASIL is difficult to determine and confirmatory techniques should be used judiciously

Prevalence, predictors, and outcomes of cardiorenal syndrome in children with dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry

BACKGROUND: The association of cardiorenal syndrome (CRS) with mortality in children with dilated cardiomyopathy (DCM) is unknown. METHODS: With a modified Schwartz formula, we estimated glomerular filtration rates (eGFR) for children ≥1 year old with DCM enrolled in the Pediatric Cardiomyopathy Registry at the time of DCM diagnosis and annually thereafter, and defined CRS as an eGFR <90 mL/min/1.73 m(2). Children with and without CRS were compared on survival and serum creatinine concentrations (SCr). The association between eGFR and echocardiographic measures was assessed with linear mixed-effects regression models. RESULTS: Of 285 eligible children with DCM diagnosed at ≥1 year of age, 93 were evaluable. CRS was identified in 57 (61.3%). Mean (SD) eGFR was 62.0 (22.6) mL/min/1.73 m(2) for children with CRS and 108.0 (14.0) for those without (P<0.001); median SCr concentrations were 0.9 and 0.5 mg/dL, respectively (P<0.001). The mortality hazard ratio of children with CRS vs. no CRS was 2.4 (95% CI: 0.8-7.4). eGFR was positively correlated with measures of left ventricular function and negatively correlated with age. CONCLUSIONS: CRS in children newly diagnosed with DCM may be associated with higher 5-year mortality. Children with DCM, especially those with impaired left ventricular function, should be monitored for renal disease