Malan syndrome: Sotos-like overgrowth with de novo NFIX sequence variants and deletions in six new patients and a review of the literature

De novo monoallelic variants in NFIX cause two distinct syndromes. Whole gene deletions, nonsense variants and missense variants affecting the DNA-binding domain have been seen in association with a Sotos-like phenotype that we propose is referred to as Malan syndrome. Frameshift and splice-site variants thought to avoid nonsense-mediated RNA decay have been seen in Marshall–Smith syndrome. We report six additional patients with Malan syndrome and de novo NFIX deletions or sequence variants and review the 20 patients now reported. The phenotype is characterised by moderate postnatal overgrowth and macrocephaly. Median height and head circumference in childhood are 2.0 and 2.3 standard deviations (SD) above the mean, respectively. There is overlap of the facial phenotype with NSD1-positive Sotos syndrome in some cases including a prominent forehead, high anterior hairline, downslanting palpebral fissures and prominent chin. Neonatal feeding difficulties and/or hypotonia have been reported in 30% of patients. Developmental delay/learning disability have been reported in all cases and are typically moderate. Ocular phenotypes are common, including strabismus (65%), nystagmus (25% ) and optic disc pallor/hypoplasia (25%). Other recurrent features include pectus excavatum (40%) and scoliosis (25%). Eight reported patients have a deletion also encompassing CACNA1A, haploinsufficiency of which causes episodic ataxia type 2 or familial hemiplegic migraine. One previous case had episodic ataxia and one case we report has had cyclical vomiting responsive to pizotifen. In individuals with this contiguous gene deletion syndrome, awareness of possible later neurological manifestations is important, although their penetrance is not yet clear.     

The Research Board of the European Dialysis and Transplantation Nurses Association/European Renal Care Association (EDTNA/ERCA)

The Research Board (RB) of EDTNA/ERCA is a multidisciplinary group, established by the participation of renal care centres all around Europe. The RB also works with the association's Special Interest Groups (SIGs) on developing guidelines for implementing safe renal clinical practice. It is composed of six permanent members, with co-opted experts from specific fields. This article describes how the RB works and the projects implemented since 1996.     

Prediction of improvement of ventricular function after revascularization: 18F-fluorodeoxyglucose single-photon emission computed tomography vs low-dose dobutamine echocardiography

AIMS: To compare assessment of myocardial flow and glucose metabolismby single-photon emission computed tomography (SPECT) with low-dosedobutamine echocardiography in predicting improvement in regionaland global left ventricular function after coronary artery bypassgrafting. METHODS AND RESULTS: Thirty patients with regional wall motion abnormalities (meanejection fraction 32±19%) were studied with low-dosedobutamine echocardiography (5 and 10 µg . kg^–1.min^–1) and thallium-201/ ¹⁸F-fluorodeoxyglucose(FDG) SPECTprior to surgery. For comparative analysis, a 13-segment modelwas used. Postoperative improvement was predicted if the echocardiogramshowed that wall motion abnormalities were reversible duringthe dobutamine infusion and there was normal perfusion or relativelyincreased FDG uptake in perfusion defects (mismatch) in dyssynergicsegments on SPECT. After surgery, ventricular function was reassessed.An echocardiogram was taken at the 3 month follow-up with thepatient at rest. Regional wall motion had improved in 62/168(37%) revascularized segments. In predicting functional outcome,low-dose dobutamine echocardiography reached a sensitivity of89% and a specificity of 82%, with a positive predictive valueof 74% and a negative predictive value of 93%, whereas for thallium-201/FDGSPECT these values were 84%, 86%, 78% and 90%, respectively.In patients with more than two viable segments on either technique,the wall motion score index, a surrogate of global ventricularfunction, improved significantly. CONCLUSION: For the optimal prediction of functional out-come, combinedassessment of flow and FDG imaging is needed. Both thallium-201/FDGSPECT and low-dose dobutamine echocardiography appear comparableand similarly accurate in predicting improvement of left ventricularfunction after surgical revascularization.     

European study on epidemiology and the management of HCV in the haemodialysis population--Part 1: centre policy

Haemodialysis patients are known to be at risk of infection of Hepatitis C Virus (HCV) through nosocomial spread. This paper presents the first part of a study on epidemiology and management of HCV, in a haemodialysis population, conducted by the EDTNA/ERCA Research Board. Data on HCV management and infection control procedures was collected from 136 European centres using an electronic questionnaire. The study identifies a number of possible risk factors for transmission of the virus: failing to disinfect devices between patients, sharing of single-use vials to prepare drugs or infusions for different patients, inadequate sterilisation or cleaning of machines between dialysis sessions, unsatisfactory environmental cleaning and distance less than one metre between chairs.     

Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction

Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency.

Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses.

Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses.

Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.     

Comparison of effects on systolic and diastolic left ventricular function of nebivolol versus atenolol in patients with uncomplicated essential hypertension

This was a double-blind, randomized, prospective study comparing the effects of nebivolol and atenolol on systolic diastolic left ventricular function in patients with essential hypertension. A significant difference was seen in stroke volume between these 2 drugs. The blood pressure lowering effect of atenolol was strongly related to cardiac output and heart rate reduction. The blood pressure lowering effect of nebivolol was related to a reduction in peripheral resistance and an increase in stroke volume with preservation of cardiac output. This preservation of cardiac output, together with a reduced peripheral resistance, may be potentially important in treating heart failure.     

Studies on isolated rat adrenal cells. I. Continuous flow and batch incubation.

A procedure for the continuous flow incubation of isolated adrenal cells is described. In this way the advantages of continuous flow incubations of adrenal tissue are combined with those of isolated adrenal cells. Suspensions of isolated adrenal cells were prepared by a modification of the collagenase method. A sigmoid dose-response curve was obtained when these cells were incubated with ACTH in batch incubations. Under these conditions (in the presence of 1 mU ACTH/ml) the corticosterone production rate remained constant during at least 240 min. This production rate was linearly related to the number of cells. Pre-incubation of the cells during 3 h resulted in an increased response to ACTH. In continuous flow incubations without ACTH the corticosterone production was negligible. With 100 mu U ACTH/ml corticosterone production increased sharply after a short lag period. A maximum was reached after 60-75 min followed by a slow decrease. Cells pre-incubated in the continuous flow apparatus had a slightly diminished ACTH response without loss of affinity to ACTH. The continuous flow incubation of isolated adrenal cells offers new possibilities for the dynamic study of steroid biosynthesis in vitro. The method may also be valuable to study processes in a wide variety of other tissues.