Genome wide analysis in a discordant monozygotic twin with caudal appendage and multiple congenital anomalies.

Caudal appendage is a rare dysmorphic feature of which etiologic mechanisms are not well understood. Here we report monozygotic (MZ) twin brothers who are discordant for the caudal appendage and multiple congenital anomalies. Twins were the product of a 33 weeks of gestation, monochorionic-diamniotic pregnancy. On admission the proband had micrognathia, beaked nose, hypospadias, caudal appendage and juxtaductal aorta coarctation. At birth, he was small for gestational age and he had transient hypothyroidism which was detected in the newborn period. Karyotype analysis showed 46,XY. Monozygosity was shown by 15 microsatellite markers plus amelogenin (AmpFlSTR Identifiler PCR Amplification Kit, Applied Biosystems). Genome-wide copy number analysis of the twins by DNA-DNA hybridization of whole genomic DNA (NimbleGen Human CGH 385K WG-T v2.0 array) showed a significant difference at two neighboring probes with Log2 ratio: 0.72088 which are located on chromosome 3p12.3. Further analysis by high resolution of chromosome 3 array (Roche NimbleGen Human HG18 CHR3 FT Median Probe Spacing 475 bp) and quantitative PCR analysis did not confirm the deletion.

Syncope or seizure? The diagnostic value of synchronous tilt testing and video-EEG monitoring in children with transient loss of consciousness.

Syncope and seizure are frequently encountered problems in daily neurology practice, and they also share common findings such as transient loss of consciousness and atonia. Sometimes, it is difficult to make a differentiation between the two entities using only clinical findings. In this study, nineteen patients aged between 5 and 20 years who had recurrent transient loss of consciousness and occasional atonic events were examined with synchronous tilt testing and video-EEG recordings. Eleven patients were initially diagnosed with epilepsy, and they were given antiepileptic drugs. Eight patients displayed neurally mediated syncope during examination. Four of the eight patients had cardioinhibitory syncope type 2B. Three-fourths of the patients with syncope had been initially diagnosed with epilepsy and were prescribed antiepileptic drugs. One patient with cardioinhibitory syncope who had prolonged asystole and frequent attacks needed a cardiac pacemaker. Following implantation, she had no new attacks. Synchronous tilt testing and video-EEG recordings give more information than doing them separately, and they are helpful in the differential diagnosis of syncope and seizure.

Lack of association between TNFalpha gene polymorphism at position -308 and risk of acute rheumatic fever in Turkish patients.

OBJECTIVE: Acute rheumatic fever (ARF) is a multisystem inflammatory disease process that follows nasopharyngeal infection caused by group A streptococcus (GAS) (Streptococcus pyogenes). Recent studies have demonstrated that allelic variations at the tumour necrosis factor alpha (TNFalpha) locus are involved in the nature of rheumatic diseases such as juvenile idiopathic arthritis and rheumatic heart disease. Thus, TNFalpha polymorphisms at -308 in ARF patients might be useful in contributing to identification of the primary factors associated with pathogenesis of ARF. METHODS: We performed a case-control association study between the common G/A promoter polymorphism at position -308 in the TNFalpha gene and ARF in Turkish patients, investigating whether this locus acts as a risk factor or has a modifying effect. RESULTS AND CONCLUSION: Previous studies have reported that TNFalpha plays a major role in the pathogenesis of a number of autoimmune and inflammatory diseases. Moreover, significantly elevated TNFalpha levels were reported in patients with ARF. However, in our sample of patients with ARF (n = 66), no such association was found. No interactive effect was found between the TNFalpha polymorphism at position -308 and no association was detected with disease progression. These findings suggest that the role of TNFalpha in ARF may be in linkage disequilibrium with some other severity genes not yet genetically determined.

Inferior vena cava indices determine volume load in minimal lesion nephrotic syndrome.

The pathogenesis of edema in nephrotic syndrome has not been entirely understood. We investigated the value of the echographic parameters [inferior vena cava index (IVCI), inferior vena cava collapsibility index (IVCCI), and left atrium diameter (LAD)] to determine the volume load in children with minimal lesion nephrotic syndrome (MLNS). Twelve children with MLNS (seven boys, five girls) were included in this study. The patients were classified into three different stages (stage A: edematous; stage B: 50% decrease in weight gain; stage C: edema free) following measurement of their ideal weights. The ideal weight of patients in stage A was increased 13 +/- 7%. Serum total protein, albumin and urine sodium levels were found to be low in these patients. Plasma renin activity (PRA) and serum aldosterone levels in stage A were significantly different from those of the control group (P<0.05). PRA and serum aldosterone levels were not different from those of the control group in stage B (P>0.05). However, the increase in PRA was significant in stage C. Although a significant weight decrease was found in stages B and C, it had no effect on IVCI, LAD, and cardiothoracic index. We consider IVCI, IVCCI, and LAD measurements by echocardiography (ECHO) to be easy and reliable clinical methods for assessing the intravascular volume load in patients with MLNS.

Influence of feeding regimens on non-invasive inferior vena cava and hepatic vein velocity measurements in infants.

UNLABELLED: The aim of this study was to investigate the effects of feeding type and osmotic load on intravascular volume status. Ninety term, healthy infants 2 mo of age were included in the study. The breastfed and formula-fed groups each consisted of 45 infants. Echocardiographic examination was performed before and after feeding. The collapse index of the inferior vena cava (IVCIC) and right atrial pressure (RAP) were calculated. No statistically significant differences were found between before- and after-feeding values of IVCIC, RAP and hepatic vein velocities in breastfed infants. In the formula-fed group, after-feeding values of IVCIC were significantly lower and RAP, hepatic vein systolic and diastolic velocities were significantly higher compared to the before-feeding values. Most of the mothers (78%) were unsuccessful at preparing the formula at appropriate concentrations. No statistically significant differences were found between the before-and after-feeding values of IVCIC, RAP and hepatic vein velocities in infants being fed appropriately prepared formula. The after-feeding values of hepatic vein velocities were higher than those of before-feeding values; after-feeding values of IVCIC were lower than before-feeding values in infants being fed highly concentrated formula. CONCLUSION: The values of inferior vena cava indices and hepatic vein velocities were not effected by feeding in infants receiving appropriately concentrated formula, like those of infants receiving breast milk. However, feeding with highly concentrated formula may cause intravascular volume expansion.

Doppler echocardiography in adenotonsillar hypertrophy.

OBJECTIVE: Adenotonsillar hypertrophy causing upper airway obstruction may lead to the pulmonary hypertension and cor pulmonale. This study aimed to clarify the diagnostic methods of this complication, besides polysomnography, to find another objective criterion for surgical intervention and to demonstrate the curative effect of adenotonsillectomy on this complication using this objective criterion. METHODS: We studied the outcomes of 17 children with pulmonary hypertension secondary to the adenotonsillar hypertrophy. Pulmonary arterial pressure measurement was performed noninvasively by Doppler echocardiography. RESULTS: Mean preoperative pulmonary arterial pressure was 29.12+/-4.41 mmHg and decreased dramatically after relief of upper airway obstruction by adenoidectomy and/or tonsillectomy to the normal level of 12.06+/-3.09 mmHg. These results were analyzed by equal variances t-test and found very significant (P<0.01). Regarding the symptoms of upper respiratory obstruction, symptom scores of these children decreased very significantly and were analyzed by equal variances t-test (P<0. 01) in the postoperative period. For all the symptoms individually (snoring, mouth-breathing during sleep and daytime, hyponasal voice, restless sleeping, daytime somnolence, enuresis nocturna), comparing percentages of preoperative and postoperative symptoms by unequal variances t-test, we obtained very significant decrease (P<0.01). CONCLUSIONS: This study illustrates that Doppler echocardiography is a safe, practical and noninvasive-method in diagnosing cardiovascular disturbances--one of the complications of adenotonsillar hypertrophy and especially for measuring the pulmonary arterial pressure. All the symptoms and disorders due to the adenotonsillar hypertrophy may be reversible by performing early adeno- and/or tonsillectomy.

A case of Lafora's disease associated with cardiac arrhythmia.

Progressive myoclonic epilepsies are rare, genetically transmitted diseases characterized by epileptic seizures, myoclonus, and progressive neurologic deterioration. Unverricht-Lundborg disease, Lafora's disease, neuronal ceroid lipofuscinosis, mitochondrial disorders, and sialidosis are included in this group. Lafora's disease is a progressive disorder of the central nervous system with onset in the late first or second decade of life and is inherited in an autosomal-recessive pattern. The first clinical manifestation is generalized tonic-clonic seizures, myoclonus, or both, usually seen between the ages of 11 and 18 years. The other clinical manifestations are progressive dementia and limb ataxia. Diagnosis is based on showing the typical inclusions in the brain, liver, skin, or muscle tissue specimens. The case of a 6-year-old male patient, who was admitted with the clinical findings of third-degree atrioventricular block and dementia and eventually diagnosed with Lafora's disease, is presented.

The CHARGE association in a newborn infant.

CHARGE association is the nonrandom association of congenital anomalies, including choanal atresia, coloboma, heart defects, retardation of growth and development, genital hypoplasia and ear abnormalities. We report a male newborn infant with CHARGE association. Other congenital abnormalities include micrognathia, high-arched palate, facial asymmetry, broad nasal bridge, hypertelorism, asymmetric eye size, and left microphthalmia. On radiologic examination, hemivertebrae were detected on the thoracal vertebrae. Although both autosomal and recessive transmission have been reported, most cases of CHARGE association have been sporadic (karyotype analysis is generally reported to be normal as in our patient). Transmission and recurrence risk of this association are not known. The presence of choanal atresia and/or coloboma must alert the clinician to search for other abnormalities for diagnosis of CHARGE association.

Spondylocostal dysplasia and cardiac anomalies in one dizygotic twin.

A 13-day-old, preterm, male infant was referred for respiratory distress syndrome (RDS) and jaundice. His twin sister had died of RDS on the second day of life in another hospital. The patient had typical features of spondylocostal dysplasia. Ventricular septal defect (VSD) and patent ductus arteriosus (PDA) were also diagnosed by echocardiographic evaluation. Parental consanguinity was not reported. There were no other similar cases in the family, and his twin sister and five-year-old living sister were free of deformities. Therefore, autosomal-recessive transmission may be considered first; however, because the patient was the only affected individual in this family, second denovo autosomal-dominant mutation should also be considered. This is the first reported case of spondylocostal dysplasia with VSD and PDA to our knowledge.

The influence of feeding regimens on endogenous digoxin-like immunoreactive substance concentrations in infants.

The aim of this study was to investigate serum digoxin-like immunoreactive substance (DLIS) levels in 60 healthy term infants when they reached 1-6 months of age with regard to feeding regimen. Group I consisted of 30 infants fed exclusively on breast milk. Groups II and III each consisted of 15 infants fed on formula and cow's milk, and on formula and cow's milk supplemented by breast milk, respectively. Mean serum DLIS concentrations were 0.03 +/- 0.05, 0.18 +/- 0.09 and 0.15 +/- 0.09 ng/ml in groups I-III, respectively. The difference between the DLIS levels in groups II and III was not significant. Serum DLIS levels of infants in groups II and III, on the other hand, were significantly higher than in group I (p < 0.05). These findings were interpreted to suggest that artificial nutrients may cause volume expansion and an increase in endogenous DLIS levels. The latter response is possibly a protective mechanism to decrease volume expansion in groups II and III.

Lymphocyte subsets and plasma IL-1 alpha, IL-2, and TNF-alpha concentrations in acute rheumatic fever and chronic rheumatic heart disease.

The distribution of CD3+, CD4+, CD8+, CD19+, CD16+, and CD25+ lymphocyte populations in peripheral blood as well as the plasma concentrations of interleukin-1 alpha (IL-1 alpha), and IL-2 and tumor necrosis factor alpha (TNF-alpha) were investigated in 25 children with acute rheumatic fever (ARF) at the time of admission and after 3 months and in 15 children with chronic rheumatic heart disease (CRHD) and in 15 children with streptoccocal pharyngitis (SP) in order to determine changes in lymphocyte subsets and cytokine concentrations occurring during different stages of the disease. The percentages and absolute counts of CD4+, CD16+, CD25+ cells, the ration of CD4/CD8 and plasma concentrations of IL-1 alpha and IL-2 in patients with ARF were significantly higher at admission than 3 months later. These levels were also significantly higher than in patients with CRHD, SP, or normal controls. Production of IL-2 in ARF and CRHD patients directly correlated with the percentages of CD4+ and CD25+ cells. According to our results, the evidences of increased cellular immune response in ARF are increased percentages CD4+ and CD25+ cells, CD4/CD8 ratio, and increased plasma concentrations of IL-1 alpha and IL-2. Furthermore, activation of cellular immune response was not present throughout all stages of rheumatic heart disease and also in SP.