Chudley-McCullough Syndrome: Variable Clinical Picture in Twins with a Novel GPSM2 Mutation.

Chudley-McCullough syndrome (CMS) is a rare autosomal recessive disorder characterized by sensorineural deafness, agenesis of the corpus callosum, frontal polymicrogyria, interhemispheric cyst, and ventricular enlargement. CMS is caused by mutations in the GPSM2 gene, but until now no more than eight different mutations are on record. We describe two dizygotic twins with a novel homozygous loss-of-function mutation (c.1093C > T; p.Arg365*). While one child developed hydrocephalus-prompting shunt implantation immediately after birth, the other sibling did not. The combination of sensorineural hearing loss and partial agenesis of the corpus callosum is a highly recognizable clinico-radiological entity that should prompt mutational analysis of the GPSM2 gene.

Altered diastolic left atrial and ventricular performance in asymptomatic patients after repair of tetralogy of Fallot.

We evaluated the interaction of left atrial and ventricular diastolic performance in asymptomatic children and young adults after ToF-repair (n=25). Those young people, as well as 25 age matched healthy children and young adults were examined using non-invasive conventional echocardiography. Regional systolic and diastolic myocardial strain and strain rate in left atrium and ventricle were analysed using 2D-speckle-tracking (Vivid VII, EchoPacGE). We collected planimetric data about the left atrial and ventricular performance during systole (volumetric LVEF, LV-Tei-Index, MV-E/E'-Ratio) and diastole (LAEF, LVEDV, left atrial volume). Registration of right pulmonary-venous inflow-patterns during ventricular systole, diastole and active atrial contraction was used to support assessment of left atrial function. To verify the timing of left atrial contraction and possible electromechanical delay we measured several ECG-related time-intervals. Statistical analysis included Mann-Whitney-U-Test, Bonferroni-Holm-Test and two-tailed Spearman-Correlation. Systolic pulmonary-venous inflow in ToF-patients was not different compared to the controls. Early diastolic pulmonary-venous inflow was significantly higher in ToF-patients as well as the LV-Tei-Index. The MV-E/E'-ratio, which is closely related to LVEDP, was significantly higher in ToF-patients and correlated with the early diastolic pulmonary venous inflow parameters such as the maximum diastolic bloodflow speed. Diastolic left atrial and ventricular strain and strain rate in ToF-patients did not differ from those in the controls. During late diastole there was a significantly premature timing of maximum myocardial strain rate of the interatrial septum and time-ratio of P-wave origin to maximum reverse pulmonary-venous blood flow and the duration of one heart action. Furthermore the maximum late diastolic reverse pulmonary-venous blood flow was significantly higher in ToF-patients. Those observations indicate a premature active left atrial contraction in late diastole in ToF-patients compared to the controls. In asymptomatic young patients after ToF-repair earlier and increased left atrial contraction was found, which may indicate adaptive compensatory mechanisms to overcome latent and asymptomatic altered systolic and diastolic left ventricular performance. Extensive assessment of left atrial parameters including the pulmonary veins should be considered in terms of an entire evaluation of left heart function in patients after ToF-repair.

Growth differentiation factor 15--an early marker of abnormal function of the Fontan circuit in patients with univentricular hearts.

BACKGROUND: In patients after the Fontan procedure, assessment of ventricular function is difficult and amino-terminal pro-B-type natriuretic peptide levels failed to be directly related to echocardiographic measures of systolic ventricular function. The aim of the study was to evaluate growth differentiation factor 15 (GDF-15), a marker of various stress pathways in the heart and extracardiac tissues. METHODS: Plasma GDF-15 levels were measured in 38 consecutive patients after the Fontan procedure and compared to clinical, echocardiographic, and laboratory data; liver tissue stiffness; and venous hepatic flow velocities. RESULTS: Mean GDF-15 levels were 987.2±440.5 pg/mL in patients with an ejection fraction (EF)<50% as compared to 520.2±143.1 pg/mL in those with an EF≥50% (P<.001). Growth differentiation factor 15 levels were significantly related to the EF of the single ventricle (r=-0.66, P<.001), New York Heart Association functional class (r=0.43, P=.008), and γGT levels (r=0.50, P=.002) but weakly to liver tissue stiffness. According to receiver operating characteristic curve analysis, an EF<50% was best predicted by GDF-15 levels (area under the curve [AUC] 0.90, P<.001), peak venous hepatic flow at deep inspiration (AUC 0.89, P=.002), and age at Fontan operation (AUC 0.86, P=.001). Growth differentiation factor 15 and age at Fontan operation proved to be independent predictors in the multivariate analysis. The optimal cutoff of GDF-15 for the prediction of an EF<50% was calculated to be 613 pg/mL with a sensitivity of 90.0% and specificity of 85.7%. CONCLUSIONS: Growth differentiation factor 15 might be helpful in detecting early abnormal function of the Fontan circuit in patients with univentricular hearts. In patients with GDF-15 levels exceeding 613 pg/mL, further cardiac evaluation should be considered because impaired systolic function of the single ventricle may be present.