Iranian Journal of Pediatrics
Volume:23 Issue: 4, Aug 2013

Genetic disorders are traditionally categorized into three main groups: single-gene, chromosomal, and multifactorial disorders. Single gene or Mendelian disorders result from errors in DNA sequence of a gene and include autosomal dominant (AD), autosomal recessive (AR), X-linked recessive (XR), X-linked dominant and Y-linked (holandric) disorders. Chromosomal disorders are due to chromosomal aberrations including numerical and structural damages. Molecular and cytogenetic techniques have been applied to identify genetic mutations leading to diseases. Accurate diagnosis of diseases is essential for appropriate treatment of patients, genetic counseling and prevention strategies. Characteristic features of patterns of inheritance are briefly reviewed and a short description of chromosomal disorders is also presented. In addition, applications of cytogenetic and molecular techniques and different types of mutations are discussed for genetic diagnosis of the pediatric genetic diseases. The purpose is to make pediatricians familiar with the applications of cytogenetic and molecular techniques and tools used for genetic diagnosis.

Febrile seizure (FS) as the most common form of seizures in childhood, affects 2-5% of all children across the world. The present study reviews available reports on FS recurrence frequency and evaluates its associated risk factors in Iran. We searched the Persian database such as: SID, MagIran, Medlip, Irandoc, Iranmedex as well as English databases PubMed, ISI, and Scopus. Random effects models were used to calculate 95% confidence intervals. Meta regression was introduced to explore the heterogeneity between studies. The overall FS recurrence rate was 20.9% [95% confidence interval (CI): 12.3-29.5%]. The frequency of FS simple and complex types was 69.3% (95% CI: 59.5-79.0) and 25.3% (95% CI: 19.6-31.0), respectively. A positive familial history of 28.8% (95% CI: 19.3-38.4%) was observed for childhood FS including 36.2% (95% CI: 27.3-39.6%) for the simple and 29.4% (95% CI: 23.1-33.5%) for the complex type. The heterogeneity of recurrent FS was significantly affected by sample size (P=0.026). Almost one-third of FS children had a positive familial history. The increased risk of recurrence in patients with symptomatic seizures needs to be fully considered by parents, physicians, nurses and health policy makers.

Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance (IR) and the metabolic syndrome by a number of researchers in various populations. However, controversies are present among different studies, which might be due to the differences between various ethnic, age, and sex groups. This study aimed to determine whether RBP4 can be assumed as a marker of IR and the metabolic syndrome in the Iranian obese children. In the present longitudinal cross-sectional study, 100 5-17 years old obese children were recruited from January 1, 2011 to February 1, 2012. The patients’ information including the demographic variables, health status and behavior, and daily physical activity were collected. Moreover, serum RBP4 was measured and correlated with the homeostasis model assessment of IR index (HOMA-IR), components of the metabolic syndrome, and lipoprotein metabolism. The results revealed a positively significant correlation between RBP4 and the HOMA-IR index (P=0.02). Partial Spearman test also revealed a significant correlation between RBP4 plasma concentrations and the components of the metabolic syndrome, including waist circumference, systolic (but not diastolic) blood-pressure, and fasting blood sugar (P<0.05). However, no significant correlation was observed between RBP4 and HDL (P=0.3) as well as triglycerides concentration (P=0.1). Moreover, plasma RBP4 level gradually increased with the increasing number of the metabolic syndrome components. Regarding the results of the present study and previous investigations, RBP4 seems to be a suggestible predictive marker for both insulin resistance and metabolic syndrome in Iranian obese children; however, further studies are needed to be conducted among different ethnicities and age groups in order to determine the predictive value of this correlation.

To evaluate early aggressive vs. conservative nutrition and their effects on ROP in < 32 weeks of gestation neonates. A prospective, randomized, clinical study was conducted in NICU with a total of 75 preterm infants. In the intervention group, infants were started on early aggressive nutrition immediately after birth, in the control group infants were started on conventional parenteral nutrition. Blood samples were obtained for IGF-I and IGFBP3 levels before commencement of the parental nutrition (PN) on the first postnatal day, and from week 1 to 6 every week. The retinas of all the infants were examined for ROP. Infants in the early aggressive group had a reduction in the risk of ROP of 5% (2 from 40); the number needed to treat averaged 3.7 (2.7 to 5.2). A total of 11 neonates in the conventional group were detected as having ROP (P< 0.05). Overall, IGF-I levels were higher in the aggressive PN versus the conventional PN. ROP development was higher in the CPN compared to the APN. IGF-I levels were lower in ROP developers compared with non-ROP in the APN group. There was no difference in IGF-I levels in ROP developers versus non-ROP in the CPN group. IGF-I levels were lower in the CPN group compared with the APN group in the third week in ROP developers. There was a correlation between ROP and IGF-I levels. Through ROC analysis, IGF-I was demonstrated as being a sensitive marker for ROP. IGF-I levels were higher in the aggressive PN group versus the conventional PN group. This may indicate that IGF-I levels simply being higher is not enough; rather, that being higher above a cutoff value may prevent ROP.

Patent ductus arteriosus (PDA) is one of the most congenital heart disease. Closure is recommended because of the risk of infective endocardis, congestive heart failure, pulmonary obstructive vascular disease, morbidity and mortality in the long term. The aim of this study was to assess the long term results of the transcatheter closure of PDA in infants using Amplatzer duct occlude (ADO). From May 2004 to September 2011, forty eight infants underwent transcatheter closure of patent ductus arteriosus. A lateral or left anterior view aortogram was made to locate PDA and to measure its size. Before release of ADO, repeat aortogram was performed to evaluate for residual shunt and to confirm the appropriate deployment of the ADO. Follow up evaluations were done with transthoracic echocardiography at discharge, 1 month, 6 month, 12 month and yearly therefore. The mean age of patients at procedure was 9.18+2.32 (range 3 to 12 month), mean weight was 6.73+1.16kg (range 4.5 to 10.1 kg), median diameter of PDA was 5 mm (range 3.0 to 9 mm) and median diameter of ADO was 4 mm (range 4 to 10mm). The average fluoroscopy and procedure time were 6.23+2.9 min (range 2.7 to 17min) and 48.68+9.62 min (range 28 to 69min). The devices were deployed successfully and occluded the PDA completely in 20 out of the 48 patients immediately after procedure. Twenty four patients had trivial or mild shunt and two patients had moderate residual shunt which disappeared within 24 hours and one patient with moderate shunt in 1 month respectively. One unrelated procedure death because of the aspiration pneumonia occurred 5 days after discharge. One patient (age 8 months) had mild LPA stenosis. The device emobolization occurred immediately after the procedure in one patient. The long term results suggested that transcatheter closure of PDA using Amplatzer duct occluder is a safe and effective treatment in infants under 1 year of age with minimal complications.

Constipation is a major debilitating problem in children. We aimed to assess the serum lead levels of 2-13 year-old children complaining from constipation who referred to our center in Guilan province, Northern Iran. This cross-sectional study was done on ninety 2-13 year-old children referring to 17th Shahrivar Hospital, complaining from constipation (case group) and 90 healthy children The demographic data as well as the children’s serum lead levels were evaluated and recorded. Data were analyzed using SPSS software. Chi-square test was used as applicable. Lead poisoning was significantly more frequent in the case group (37.8%) compared with the control group (8.9%). The frequency of lead poisoning in the case group compared with the control group, was significantly higher in children <7 years old (40.2% vs. 10%), boys (40.9% vs. 9.3%), girls (34.8% vs 8.3%), residents of old houses (43.1% vs. 9.7%), residents of new houses (28.1% vs. 8.5%), residents of low-traffic areas (26.8% vs. 5.3%), urban residents (40.5% vs. 9.9%), children whose fathers had low risk (33.3% vs. 10.9%) and high risk jobs (40.7% vs. 3.8%). The frequency of lead poisoning was higher in children suffering from constipation. No significant difference was found between the two groups with respect to their sex, age, father’s job, and living in urban or rural areas.

The purpose of this study was to examine the relationship between fat patterning, age and body composition, among urban South African children in Pretoria, Central. Samples for the study comprised 1136 participants (548 boys and 588 girls) and 581 black and 555 white drawn from 12 primary schools in Pretoria Central. Anthropometrical measurements include stature, body mass and eight skinfolds: triceps, subscapular, biceps, supraspinal, abdomen, front thigh, iliac crest and medial calf. Principal components analysis technique was applied to examine the components loadings. An eigenvalue of >1.0 was retained for analysis. Pearson’s correlation coefficient was used to determine the relationship of fat patterning scores, age and body composition measures. Three principal components emerged. The first principal component was a size component (fatness), accounting for 62.3% variance. The second component (central-peripheral patterning) accounted for the total variance of 14.1%. The third component (lower trunk-upper extremity) of relative subcutaneous fat distribution, explained about 10.2% of the total residual variance. Overall, the three components account approximately for 87.0% of the total variance. The correlation coefficients indicating probabilities demonstrated that the overall body fatness (PC1), but not PC2 or PC3 was significantly correlated with body mass index (r=0.745, P<0.01), FM (r=0.672, P<0.01), fat-free mass (r=0.583, P<0.01), Percentage body fat (r=0.701, P<0.01) and children’s age (r=0.062, P<0.05). The central-peripheral and upper-lower body extremity fat patterning components are discernible among the sample of South African children in Pretoria. The results indicated that principal component 1, but not 2 and 3 was significantly correlated with body composition variables and age, suggesting that component 1 is truly an indicator of total body fatness and not fat patterning.

We examined the preventive effect of probiotic and antibiotics versus antibiotics alone, in children with recurrent urinary tract infections (RUTI) in a preliminary randomized clinical trial. Between March 2007 and April 2011, children with the history of RUTI and unilateral vesicoureteral reflux (VUR) were randomly assigned to receive concomitant probiotic and antibiotics (Lactobacillus acidophilus and bifidobacterium lactis, 107/ml, as 0.25 ml/kg three times a day regimen in addition to Nitrofurantoin, 1mg/kg daily (group I). In group II, all children received conventional prophylactic antibiotics alone (Nitrofurantoin, 1 mg/kg daily). Randomization was performed via using the random numerals table in a 1:1 manner with stratification by sex, age and grade of reflux. The urine examinations were done monthly and the incidence of UTI was evaluated in these two groups. Forty-one children (age: 8.3±3.1 years) in group I and 44 children (age: 8.0±3.0 years) in group II were compared. During the course of three years, 39% in group I and 50% of participants in group II experienced RUTIs (P=0.4). Incidences of UTI - febrile and afebrile - reduced in both groups without any significant differences after two years of prophylaxis. Also, incidence of afebrile UTIs did not significantly differ (0.51±1.30 and 0.81±1.41 respectively, P=0.3); however, the incidence of febrile UTIs in particular were lower in group I (0.00±0.00 versus 0.13±0.40, P=0.03) in the last year. The consumption of probiotic and antibiotics in children with RUTI is safe and more effective in reducing the incidence of febrile UTI in comparison to prophylactic antibiotics alone.

Vesicoureteral reflux (VUR) is an important disorder that could be diagnosed in antenatal or postnatal period. The natural history of VUR seems to be different between prenatal or postnatal forms of the disease. We compared the natural history and outcome of vesicoureteral reflux in infants less than one year old diagnosed prenatally or postnatally. All infants less than 12 months old with VUR were enrolled in two groups. Group 1 composed of patients with antenatal hydronephrosis and group2, infants with diagnosis of VUR because of UTI or other postnatal problems. We followed patients for an average of 33 months. Outcome was assessed by several factors: somatic growth, need for surgery, resolution, occurrence of UTI and scar formation. We studied 236 renal units in 152 patients (70 boys, 82girls), 67 patients in group 1 and 85 patients in group2. Occurrence of recurrent UTI was 10.6% with no significant difference between two groups. Reflux resolved in postnatal group more significantly than in the other group (73% vs 49%). Scar developed similarly in both groups (15% vs 25% of renal units). Surgery performed in 7 (8.2%) of postnatal and 4 (6%) of prenatal group with no significant differences between the two groups. VUR diagnosed prenatally has similar importance and outcome as postnatal diagnosed one. We suggest performing the same imaging and treatment procedures for prenatally and postnatally diagnosed VUR.

Intelligent electronic stethoscopes and computer-aided auscultation systems have highlighted a new era in cardiac auscultation in children. Several collaborative multidisciplinary researches in this field are performed by physicians and computer specialists. Recently, a novel medical software device, Automated Auscultation Diagnosis Device (AADD), has been reported with intelligent diagnosing ability to differentiate cardiac murmur from breath sounds in children with normal and abnormal hearts due to congenital heart disease. The aim of this study is to determine efficiency, sensitivity and specificity of the diagnoses made by this AADD in children with and without cardiac disease. We performed a cross-sectional study to determine efficiency, sensitivity and specificity of diagnoses made by AADD. Our patient population was two groups of children with and without cardiac disease(563 patients and 50 normal). SPSS version 16 was used to calculate sensitivity, specificity and efficiency and descriptive analysis. Using cardiac sound recording in four conventional cardiac areas of auscultation (including aortic, pulmonary, tricuspid and mitral), AADD proved to have a ≥90 % sensitivity, specificity and efficiency for making the correct diagnosis in children with heart disease and 100% diagnostic accuracy in children with normal hearts either with or without innocent murmurs. Considering the high sensitivity, specificity and efficiency of AADD for making the correct diagnosis, application of this software is recommended for family physicians to enhance proper and timely patients’ referral to pediatric cardiologists in order to provide better diagnostic facilities for pediatric patients who live in deprived and underserved rural areas with lack access to pediatric cardiologists.

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by reduced serum level of IgG, IgA or IgM and recurrent bacterial infections. Class switch recombination (CSR) as a critical process in immunoglobulin production is defective in a group of CVID patients. Activation-induced cytidine deaminase (AID) protein is an important molecule involving CSR process. The aim of this study was to investigate the AID gene mRNA production in a group of CVID patients indicating possible role of this molecule in this disorder. Peripheral blood mononuclear cells (PBMC) of 29 CVID patients and 21 healthy controls were isolated and stimulated by CD40L and IL-4 to induce AID gene expression. After 5 days AID gene mRNA production was investigated by real time polymerase chain reaction. AID gene was expressed in all of the studied patients. However the mean density of extracted AID mRNA showed higher level in CVID patients (230.95±103.04 ng/ml) rather than controls (210.00±44.72 ng/ml; P=0.5). CVID cases with lower level of AID had decreased total level of IgE (P=0.04) and stimulated IgE production (P=0.02); while cases with increased level of AID presented higher level of IgA (P=0.04) and numbers of B cells (P=0.02) and autoimmune disease (P=0.02). Different levels of AID gene expression may have important roles in dysregulation of immune system and final clinical presentation in CVID patients. Therefore investigating the expression of AID gene can help in classifying CVID patients.

Apparent Life-Threatening Events (ALTEs) is an episode that is frightening to the observer and is characterized by some combination of apnea, color change, altered muscle tone, choking, and gagging. This study was designed to evaluate and follow up neonates who presented with clinical manifestation of an ALTE in a year. In this prospective observational study, all of the neonates with episode of ALTE who were admitted to the Children’s Medical Center (CMC) in Tehran, from June 15th 2010 to May 14th 2011 were enrolled in the study. Data from patients consisting of history, physical examinations, and paraclinical findings were recorded in a checklist and all followed up 3 to 6 months after discharge. During the study period 18 neonates were admitted due to ALTE episode(s) with mean age of 15±13 days. Nine (50%) neonates had previous attacks of ALTE. The most frequent complaint was cyanosis in 12 (67%) and apnea in 8 (44%) patients. In 10 (56%) the event lasted less than one minute, 13 (72%) were awake, 17 (95%) in supine position and 13 (72%) on their parent’s lap. Primary antagonistic impression on admission was sepsis in 11 (61%) and concomitant seizure in 5 (28%). The most common final diagnosis according to repeated physical examinations, result of paraclinical investigations and follow up was sepsis 4 (22%) and aspiration 9 (50%). ALTE recurred in none of the neonates during follow up. The rate of ALTE seems to be higher than in this study owing to high incidence of recurrent ALTE. Although most of these attacks regress spontaneously, more attention should be paid for the underlying diseases.

To evaluate the effectiveness of a Cognitive-Behavioral therapy (CBT) for suicide prevention in decreasing suicidal ideation and hopelessness in a sample of depressed 12 to 18 year-old adolescents who had at least one previous suicidal attempt. In a clinical trial, 30 depressed adolescents who attempted suicide in the recent 3 months were selected using simple sampling method and divided randomly into intervention and wait-list control groups. Both groups received psychiatric interventions as routine. The intervention group received a 12 session (once a week) of CBT program according to the package developed by Stanley et al, including psychoeducational interventions and individual and family skills training modules. All of the patients were evaluated by Scale for Suicidal Ideation, Beck's hopelessness Inventory, and Beck's Depression Inventory before the intervention and after 12 weeks. There were significant differences between the two groups regarding the scores of the above mentioned scales after 12 weeks. Fifty-four to 77 percent decreases in the mean scores of the used scales were observed in the invention group. There were no significant changes in the scores of the control wait-list group. The differences between pre- and post-intervention scores in the intervention group were significant. CBT is an effective method in reducing suicidal ideation and hopelessness in the depressed adolescents with previous suicidal attempts.

Clostridium difficile is a gram-positive, anaerobic, spore-forming bacillus. Usually it does not cause disease unless a patient who is colonized with toxin-producing strains has been treated with antibiotics, particularly those that change the anaerobic flora of the large intestine. We investigated in a prospective study intestinal colonization of C. difficile and its toxins in children with malignancy that used different antibiotics and cytotoxic drugs. One hundred fifty-two patients were included in this prospective study. Stool samples were obtained within the first 48 hours after admission and cultured for C. difficile; cytopathic effect of C. difficile was detected on HELA cells, also ELISA test was performed for detection of toxins A and B. 25% of patients had positive culture for C. difficile; 36/38 (92%) revealed positive cytopathic effect on HELA cells. No significant relation was found between age, gender, history of antibiotic consumption and C. difficile positive culture and cytopathic effect on HELA cells. The only relation was seen between cotrimoxazol and cytopathic effect on HELA cells (P=0.03). Although the rate of C. difficile colonization (25.6%) and toxigenic strains (23.7%) in admitted children in hematologic ward is high, the rate of ELISA positive test for toxin A+B was not correspond with culture and HELA cell. With respect to sensitivity and specificity of ELISA test, possibility for existence of toxin C with cytopathic effect is high in this type of patients.

The objective of the study was to evaluate the effects of exogenous surfactant on respiratory indices in term infants with respiratory failure. Consecutive 18 mechanically ventilated term infants, who received a single dose of exogenous surfactant were retrospectively included into the study. The respiratory outcome of surfactant rescue therapy was evaluated by comparing respiratory indices before and six hours after surfactant administration. Median oxygenation index (OI), mean alveolar pressure (MAP) and fraction of inspired oxygen (FiO2) values were significantly decreased (P<0.001); median arterial oxygen partial pressure (PaO2), arterial oxygen saturation (SaO2) and PaO2/FiO2 values were significantly increased six hours after surfactant treatment (P<0.001). Rescue therapy with surfactant was found to be effective in the improvement of early respiratory indices in term infants with respiratory failure.

Alexander disease (AD) is a sporadic leukodystrophy that predominantly affects infants and children and usually results in death within ten years after onset. The infantile form comprises the most of affected individuals. It presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly and frontal bossing, seizures, pyramidal signs and ataxia. The diagnosis is based on magnetic resonance imaging (MRI) findings and confirmed by GFAP gene molecular testing. GFAP gene encodes glial fibrillary acidic protein, is the only gene in which mutation is currently known to cause AD which is inherited in autosomal dominant manner. In this article we report the first two Iranian cases of infantile AD and their clinical, brain MRI and molecular findings. We report two novel mutations too in the GFAP gene that are associated with infantile form of AD. GFAP gene mutations are a reliable marker for infantile AD diagnosed according to clinical and MRI defined criteria. A genotype-phenotype correlation had been discerned for the two most frequently reported GFAP gene mutations in infantile type of AD (R79 and R239), with the phenotype of the R79 mutations appearing much less severe than that of the R239 mutations. Our findings confirm this theory.

Peters Plus syndrome (MIM 261540) is a rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor abnormalities. Mutations in the B3GALTL gene encoding the β-1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. We report here a female patient with severe manifestations of Peters Plus syndrome including facial dysmorphism and bilateral corneal opacity associated with left renal pyelo-calicial dilatation and sexual ambiguity. Total sequencing of the B3GALTL gene revealed no mutation in the patient. To our knowledge, sexual ambiguity has not previously been reported in Peters Plus syndrome so far, and renal malformation is also apparently rare in the syndrome.