A new prognostic index of severity of intellectual disabilities in Cornelia de Lange syndrome.

Cornelia de Lange syndrome is a well-known multiple congenital anomalies/intellectual disability syndrome with genetic heterogeneity and wide clinical variability, regarding the severity of both the intellectual disabilities and the physical features, not completely explained by the genotype-phenotype correlations known to date. The aim of the study was the identification of prognostic features, ascertainable precociously in the patient's life, of a better intellectual outcome and the development of a new prognostic index of severity of intellectual disability in CdLS patients. In 66 italian CdLS patients aged 8 years or more, we evaluated the association of the degree of intellectual disability with various clinical parameters ascertainable before 6 months of life and with the molecular data by the application of cumulative regression logistic model. Based on these results and on the previously known genotype-phenotype correlations, we selected seven parameters to be used in a multivariate cumulative regression logistic model to develop a prognostic index of severity of intellectual disability. The probability of a mild ID increases with the reducing final score less than two, the probability of a severe ID increases with the increasing final score more than three. This prognostic index allows to define, precociously in the life of a baby, the probability of a better or worse intellectual outcome in CdLS patients. © 2016 Wiley Periodicals, Inc.

Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.

Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood-brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m(2) decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood-brain barrier, might in the future improve the MPS II outcome.

Prognostic significance of left atrial size in patients with hypertrophic cardiomyopathy (from the Italian Registry for Hypertrophic Cardiomyopathy).

This study assessed left atrial (LA) dimension as a potential predictor of outcome in hypertrophic cardiomyopathy (HC). From the Italian Registry for Hypertrophic Cardiomyopathy, 1,491 patients (mean age 47 +/- 17 years; 61% men; 19% obstructive), followed for 9.4 +/- 7.4 years after the initial echocardiographic evaluation, constituted the study group. The mean LA transverse dimension was 43 +/- 9 mm and was larger in patients with severe symptoms (48 +/- 9 mm for New York Heart Association classes III and IV vs 42 +/- 9 mm for classes I and II, p <0.001), atrial fibrillation (47 +/- 9 vs 42 +/- 8 mm in sinus rhythm, p <0.001), and left ventricular outflow obstruction (46 +/- 9 mm for >or=30 mm Hg at rest vs 42 +/- 9 mm for <30 mm Hg at rest, p <0.001). On univariate analysis, each 5-mm increase in LA size was associated with a hazard ratio (HR) of 1.2 for all-cause mortality (p <0.0001). On multivariate analysis, a LA dimension >48 mm (the 75th percentile) had a HR of 1.9 for all-cause mortality (p = 0.008), 2.0 for cardiovascular death (p = 0.014), and 3.1 for death related to heart failure (p = 0.008) but was unassociated with sudden death (p = 0.81). Similar results were obtained after the exclusion of patients with atrial fibrillation (HR 1.7, p = 0.008) or outflow obstruction (HR 1.8, p = 0.003). The predictive power of LA dimension >48 mm was also validated in an independent HC cohort from the United States, with similar HRs (1.8 for all-cause mortality, p = 0.019). In conclusion, in a large cohort of patients with HC from a nationwide registry, a marked increase in LA dimension were predictive of long-term outcome, independent of co-existent atrial fibrillation or outflow obstruction. LA dimension is a novel and independent marker of prognosis in HC, particularly relevant to the identification of patients at risk for death related to heart failure.