Aygün Dindar

Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome

Background: Desmosomes are cellular junctions important for intercellular adhesion and anchoring the intermediate filament (IF) cytoskeleton to the cell membrane. Desmoplakin (DSP) is the most abundant desmosomal protein with 2 isoforms produced by alternative splicing. Methods: We describe a patient with a recessively inherited arrhythmogenic dilated cardiomyopathy with left and right ventricular involvement, epidermolytic palmoplantar keratoderma, and woolly hair. The patient showed a severe heart phenotype with an early onset and rapid progression to heart failure at 4 years of age. Results: A homozygous nonsense mutation, R1267X, was found in exon 23 of the desmoplakin gene, which results in an isoform specific truncation of the larger DSPI isoform. The loss of most of the DSPI specific rod domain and C-terminal area was confirmed by Western blotting and immunofluorescence. We further showed that the truncated DSPI transcript is unstable, leading to a loss of DSPI. DSPI is reported to be an obligate constituent of desmosomes and the only isoform present in cardiac tissue. To address this, we reviewed the expression of DSP isoforms in the heart. Our data suggest that DSPI is the major cardiac isoform but we also show that specific compartments of the heart have detectable DSPII expression. Conclusions: This is the first description of a phenotype caused by a mutation affecting only one DSP isoform. Our findings emphasise the importance of desmoplakin and desmosomes in epidermal and cardiac function and additionally highlight the possibility that the different isoforms of desmoplakin may have distinct functional properties within the desmosome.

Surgical Treatment of Cardiac Echinococcosis: Report of Eight Cases

Abstract Cardiac involvement of hydatid disease is uncommon, and establishing a diagnosis is difficult because the presenting symptoms are variable. Between 1985 and 1997, eight patients ranging in age from 8 to 56 years underwent surgical excision of cardiac hydatid cysts, located in the interventricular septum in two, the right atrium in one, and the intrapericardium in five. There was one hospital death due to septic shock, but the other seven patients recovered uneventfully.

The utility of cardiac MRI in diagnosis of infective endocarditis: preliminary results

PURPOSE We aimed to evaluate the utility of cardiac magnetic resonance imaging (MRI) for the diagnosis of infective endocarditis (IE). METHODS Sixteen patients with a preliminary diagnosis of IE (10 women and six men; age range, 4-66 years) were referred for cardiac MRI. MRI sequences were as follows: echo-planar cine true fast imaging with steady-state precession (true-FISP), dark-blood fast spin echo T1-weighted imaging, T2-weighted imaging, dark-blood half-Fourier single shot turbo spin echo (HASTE), and early contrast-enhanced first-pass fast low-angle shot (FLASH). Delayed contrast-enhanced images were obtained using three-dimensional inversion recovery FLASH after 15±5 min. The MRI features were evaluated, including valvular pathologies on cine MRI and contrast enhancement on the walls of the cardiac chambers, major thoracic vasculature, and paravalvular tissue, attributable to endothelial extension of inflammation on contrast-enhanced images. RESULTS Fourteen valvular vegetations were detected in eleven patients on cardiac MRI. It was not possible to depict valvular vegetations in five patients. Vegetations were detected on the aortic valve (n=7), mitral valve (n=3), tricuspid and pulmonary valves (n=1). Delayed contrast enhancement attributable to extension of inflammation was observed on the aortic wall and aortic root (n=11), paravalvular tissue (n=4), mitral valve (n=2), walls of the cardiac chambers (n=6), interventricular septum (n=3), and wall of the pulmonary artery and superior mesenteric artery (n=1). CONCLUSION Valvular vegetation features of IE can be detected by MRI. Moreover, in the absence of vegetations, detection of delayed enhancement representing endothelial inflammation of the cardiovascular structures can contribute to the diagnosis and treatment planning of IE.

Congenital heart disease in children with Down's syndrome: Turkish experience of 13 years.

Background — Down’s syndrome (DS) is the most common chromosomal abnormality due to a trisomy of chromosome 21 commonly associated with congenital heart defects (CHDs). This study aimed to evaluate the frequency and types of CHD patterns in Turkish children with DS. Method — The data relate to paediatric patients with DS who underwent cardiologic screening between 1994 and 2007 and were reviewed in our Paediatric Cardiology unit. Results — Four hundred and twenty-one out of the 1042 paediatric patients with DS studied over a 13-year period had associated CHD. Of these, 320 (77.6%) had a single cardiac lesion, while the remaining 92 patients (22.4%) had multiple defects. The most common single defect was an atrioventricular septal defect (AVSD) found in 141 patients (34.2%), followed by 69 patients (16.7%) showing secundum type atrial septal defect, and ventricular septal defect in 68 patients (16.5%). AVSDs were the leading type, isolated or combined with other cardiac anomalies with an overall occurrence of 19.8% of paediatric patients with DS, and 49.2% of paediatric patients with both DS and CHD. Conclusion — This is the first study concerning the frequency and type of CHD observed in Turkish children with DS.The high frequency of AVSD in Turkish children with DS implied that early screening for CHDs by echocardiography is crucial. The correction of AVSDs in paediatric patients with DS should be performed in the first 6 months of life to avoid irreversible haemodynamic consequences of the defect.

Therapeutic combination of sildenafil and iloprost in a preterm neonate with pulmonary hypertension.

While new pharmacological approaches have been demonstrated to effectively manage PH in adults, few reports have addressed PH treatment in neonates and infants. This case report describes the successful management of severe PH secondary to bronchopulmonary dysplasia, respiratory syncytial virus infection, and hypoxia in a preterm 4‐month‐old with the long‐term use of orally administered sildenafil and inhaled iloprost. Pediatr. Pulmonol. 2011; 46:617–620.

Permanent cardiac pacing in a 2.5 month-old infant with severe cyanotic breath-holding spells and prolonged asystole.

We report the case of a 2.5 month-old infant with cyanotic breath-holding spells, loss of consciousness and seizures. Prolonged asystole up to 70 s despite cardiopulmonary resuscitation was documented by 24 hour Holter monitoring. An epicardial pacemaker was implanted followed by no further loss of consciousness and seizures during spells in a six month follow-up period.

An evaluation of children with Kawasaki disease in Istanbul: a retrospective follow-up study.

BACKGROUND: Kawasaki disease (KD) is an acute, self‐limiting vasculitis of unknown etiology. The incidence of KD is increasing world wide. However, the epidemiological data for KD in Turkey has not been well described. OBJECTIVE: To describe the demographic, clinical, and laboratory features of children with KD who were diagnosed and managed in the American Hospital, Istanbul, Turkey. METHOD: Patients with KD were retrospectively identified from the hospital discharge records between 2002 and 2010. Atypical cases of KD were excluded. A standardized form was used to collect demographic data, clinical information, echocardiography and laboratory results. RESULTS: Thirty‐five patients with KD, with a mean age of 2.5±1.9 years, were identified. Eighty‐five point seven per cent of patients were under 5 years of age. A seasonal pattern favouring the winter months was noticed. In addition to fever and bilateral conjunctival injection, changes in the oral cavity and lips were the most commonly detected clinical signs in our cases. Coronary artery abnormalities were detected in nine patients. The majority of our patients had started treatment with intravenous immunoglobulin in the first 10 days of the onset of fever, and only one patient required systemic steroids for intravenous immunoglobulin‐resistant KD. The coronary artery abnormalities resolved in all nine patients within 8 months. CONCLUSION: This study is the most comprehensive series of children from Turkey with KD included in Medline. As adult‐onset ischemic heart disease may be due to KD in childhood, further prospective clinical investigations are needed to understand the epidemiology, management and long‐term follow‐up of the disease.

Volatile solvent abuse caused glomerulopathy and tubulopathy in street children

Substance misuse among street children is a significant problem in developing countries. Volatile substances are the most abused agents. According to case reports, chronic renal diseases are common among substance-abusing street children. In this study, we examined the renal findings of 42 volatile substance–abusing street children and compared them with results from 49 healthy children (control). The street children’s weight, height, and blood pressure were lower than the controls’ (P < 0.05). However, their blood alkaline phosphatase and creatinine phosphokinase levels were higher (P < 0.05), and total blood protein, creatinine, and phosphorus levels were lower than the controls’ (P < 0.05). Furthermore, the street children’s glomerular filtration rates were within normal limits (P < 0.05), their urinary N-acetyl-beta-glucosaminidase (NAG), β2-microglobulin, microalbumin, protein, calcium, phosphorus, sodium, potassium, and chloride excretions were higher, and tubular phosphate reabsorption were lower than the controls’ (P < 0.05). Volatile substances have been charged with causing distal tubular disease, but increased urinary protein, NAG, β2-microglobulin, microalbumin, and electrolyte excretions also result from glomerular, proximal, and distal tubular influences. We believe that increased volatile substance products in the renal parenchyma are responsible for glomerular and tubular damage. Volatile substance–abusing street children should be examined for glomerular and proximal tubular function and distal tubular acidosis.

Electrocardiographic markers for the early detection of cardiac disease in patients with beta-thalassemia major

OBJECTIVE To comparatively evaluate P-wave dispersion (PWD) in patients with beta-thalassemia major (TM) and healthy control subjects for the early prediction of arrhythmia risk. METHODS Eighty-one children with beta-TM, aged 4-19 years, and 74 healthy children (control group) underwent routine electrocardiography and transthoracic echocardiography for cardiac evaluation. PWD was calculated as the difference between the maximum and the minimum P-wave duration. RESULTS There was a statistically significant difference between study and control groups in peak early (E) mitral inflow velocity and E/late (A) velocity ratio. Maximum P-wave duration and PWD were found to be significantly higher in beta-TM patients than in control subjects. CONCLUSIONS Increased PWD in our beta-TM patients might be related to depression of intra-atrial conduction due to atrial dilatation and increased sympathetic activity. These patients should be closely followed up for risk of life-threatening arrhythmias.

Evaluation of coronary artery abnormalities in Williams syndrome patients using myocardial perfusion scintigraphy and CT angiography

BACKGROUND Sudden death risk in Williams syndrome (WS) patients has been shown to be 25-100 times higher than in the general population. This study aims to detect coronary artery anomalies and myocardial perfusion defects in WS patients using noninvasive diagnostic methods. METHODS This study features 38 patients diagnosed with WS. In addition to physical examination, electrocardiography, and echocardiography, computed tomography (CT) angiography and rest/dipyridamole stress technetium-99m sestamibi ((99m)Tc-sestamibi) single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) were performed. RESULTS Twenty-one (55%) patients were male; 17 (45%) were female. The average patient age was 12 ± 5 years (2.5-26 years); the average follow-up period was 7.2 ± 4.2 years (6 months-18 years). Cardiovascular abnormalities were found in 89% of patients, the most common one being supravalvar aortic stenosis (SVAS). CT angiography revealed coronary anomalies in 10 (26%) patients, the most common ones being ectasia of the left main coronary artery and proximal right coronary artery as well as myocardial bridging. SVAS was present in 80% of patients with coronary artery anomalies. (99m)Tc-sestamibi SPECT MPS revealed findings possibly consistent with myocardial ischemia in 29% of patients, and ischemia in 7 out of 10 patients (70%) with coronary anomalies shown on CT angiography (p = 0.03). CONCLUSIONS Coronary artery abnormalities are relatively common in WS patients and are often accompanied by SVAS. CT angiography and dipyridamole (99m)Tc-sestamibi SPECT MPS seem to be less invasive methods of detecting coronary artery anomalies and myocardial perfusion defects in WS patients.