Andersen-Tawil syndrome: Overlapping clinical features with Noonan syndrome?

Andersen-Tawil syndrome (ATS) and Noonan syndrome (NS) are both autosomal dominantly inherited disorders that share anomalies in the same body systems, i.e. cardiovascular system, skeleton, growth, and face morphology. Here we report a patient meeting clinical diagnostic criteria for NS in whom no variant in one of the genes known to cause NS was found and a pathogenic variant in KCNJ2 (c.653G > C, p.(Arg218Pro)) was demonstrated. Because of manifestations typical for NS and previously not described in ATS (broad neck, low hairline and pectus excavatum), this may indicate there is a phenotypical overlap between ATS and NS, although we cannot exclude that the patient has an additional, hitherto undetected variant in another gene that explains the NS features. Further studies into a functional relation between KCNJ2 and the RAS/MAPK pathway are needed to determine this further.

Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial.

BACKGROUND: Folic acid is assumed to have favourable effects on vascular endothelium, directly as well as indirectly through its effect on homocysteine metabolism. However, the clinical value of folic acid in secondary prevention after acute myocardial infarction (MI) has never been tested. Thus, a randomised, open-label, multicentre trial was performed in order to study the effect of folic acid 5 mg o.d. when added to statin therapy on the incidence of recurrent major clinical events up to 1 year post-MI. METHODS: A total of 283 patients with a total cholesterol >6.5 mmol/l (251 mg/dl) (mean 7.3 mmol/l) were included. All patients received 40 fluvastatin. In 140 of the 283 patients, folic acid (5 mg o.d.) was instituted at discharge, and the remaining 143 patients served as controls. Other secondary prevention measures for both groups were advocated. The primary endpoint was a composite consisting of all vascular events, including death, recurrent MI, strokes, and unplanned invasive coronary interventions. RESULTS: At baseline, the two groups were well-matched for all clinical and demographic parameters. After 1 year of treatment, no difference was noticed in the primary endpoint between the two groups. These endpoints occurred in 43 patients (31%) in the folic acid group, as opposed to 45 patients (31%) in the control group. All separate cardiovascular events were also equally distributed between both groups. Total cholesterol levels decreased to a similar extent in the two groups (to 5.5 and 5.7 mmol/l, in folic acid and control groups, respectively). CONCLUSIONS: In this medium-size pilot study, folic acid did not demonstrate any beneficial additive effects on cardiovascular mortality or morbidity in post-MI patients with hypercholesterolemia who were treated with statin therapy. Larger trials, possibly targeting at selected populations, must be awaited before definitive conclusions regarding the potentially favourable effects of folic acid supplementation in secondary prevention can be drawn.

Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial.

AIMS: Residual ischaemia following acute myocardial infarction (AMI) is related to an adverse outcome, although the effect of early initiation of statin therapy is unknown. METHODS: A randomized, placebo-controlled, double-blind, parallel study was performed, which compared fluvastatin 80 mg daily with placebo in patients with an AMI and total cholesterol of <6.5 mmol.l(-1). Ischaemia was measured by ambulatory electrocardiographic (AECG) monitoring over 48-h at baseline, after 6 weeks and at 12 months. RESULTS: Five hundred and forty patients were included (83% male, age 61+/-11 years); 43% had an anterior AMI and 50% were treated with fibrinolytics in the acute phase. After 12 months, the total cholesterol (TC) level was reduced by 13% and LDL-C (low-density-lipoprotein cholesterol) by 21% (from 3.5 mmol.l(-1) to 2.7 mmol.l(-1)) in the fluvastatin treatment group. Both TC and LDL increased by 9% in the placebo group (P<0.001 between groups). At baseline, ischaemia on AECG was present in only 11% of patients, and absent in 77%; in the remaining 11%, recordings were technically inadequate. After 6 weeks, 32/48 (67%), and 12 months 35/46 (76%) of the patients with ischaemia on the baseline AECG, no longer showed signs of ischaemia. Nevertheless, ischaemia at baseline was predictive for the occurrence of any major clinical event (RR=2.35; 95% CI 1.39-3.2;P <0.001). Fluvastatin treatment did not affect ischaemia on AECG, nor the occurrence of any major clinical events as compared to placebo. Post-hoc analysis in patients with the most pronounced ischaemia at baseline showed a trend for a beneficial effect of fluvastatin on major clinical events (P=0.084). CONCLUSION: Residual ischaemia after AMI is observed less frequently in the present study, than in earlier studies, although it is predictive for future cardiovascular events. As a result, the present study was underpowered, and no effect of fluvastatin on AECG ischaemia, or major clinical events in the first year after AMI, could be detected. The present data do not confirm other reports which support widespread use of statin treatment early after AMI.