Iranian Journal of Child Neurology (IJCN)
Volume:12 Issue: 1, Winter 2018

Inborn errors of metabolism are complex disorders with huge variety in clinical manifestations. Metabolic disorders have overlapping clinical pictures with other genetic disorders especially neurogenetic diseases. It causes hardship in diagnosis of metabolic and neurogenetic diseases in some occasions. There is growing rise for using whole exome sequencing in diagnosis of genetic disease during recent years result from decreasing its cost.
We reviewed articles by search in medline database to evaluate impact of whole exome sequencing in diagnosis of metabolic and neurogenetic diseases in clinic field.
Review declared whole exome sequencing is effective in recognizing metabolic and neurologic diseases especially in complex cases. Diagnostic yield of whole exome sequencing in identifying metabolic and neurogenetic disease has large variety, ranging from 16% to 68% that increase during recent years. It has ability to change patients’ management in 2-44% of cases depend on different studies. Whole exome sequencing can provide new information about new disease, new variants and phenotypes. Careful interpretation of data obtained by WES and evaluation of correlation between clinical manifestation and results is necessary for clinical application of this technology.
Whole exome sequencing is useful way for diagnosis of metabolic and neurogenetic diseases essentially in puzzling cases.

Posterior reversible encephalopathy syndrome (PRES) is characterized by typical radiologic findings in the posterior regions of the cerebral hemispheres and cerebellum. The symptoms include headache, nausea, vomiting, visual disturbances, focal neurologic deficits and seizures.
Method and We retrospectively examined 23 children with PRES. The most common precipitating factors were hypertension (78.2%) and medications, namely immunosuppressive and antineoplastic agents (60.8%). Manifestations included mental changes (100%), seizures (95.6%), headache (60.8%), and visual disturbances (21.7%) of mean 3.6 (range 1-10) day's duration. Cranial magnetic resonance imaging (MRI) showed bilateral occipital lesions in all patients, associated in 82.6% with less typical distribution of lesions in frontal, temporal or parietal lobes, cerebellum, corpus callosum, basal ganglia, thalamus, and brain stem. Of these findings, frontal involvement was predominant, observed in 56.5% of patients. Clinical recovery was followed by radiologic resolution in all patients.
PRES is often unsuspected by the clinician, thus radiologists may be the first to suggest this diagnosis on an MRI obtained for seizures or encephalopathy. Atypical MRI finding are seen quite often. Rapid diagnosis and treatment is required to avoid a devastating outcome.

Obesity is a medical condition that it may have a harmful effect on health, leading to increased illness and reduced life expectancy. This study is aimed to evaluate the relationship of psychiatry disorders in overweight and obese children and adolescents.
In this was case-control study, one hundred and sixty child and Adolescent were recruited. The sampling method of this study was non-probability and biased. Study instruments were SDQ, CDI, STAI, Peds QL. All questionnaires were self-administrating that was completed by subjects or their parents. Differences between groups were examined using t-test and chi-square tests as appropriate.
The results our study showed no significant different in scores of anxiety between two groups. But showed significant different in scores of depression, quality of life, and strength and difficult between two groups. Also there was no significant difference in gender effect on anxiety and Depression. However, in Quality of life test showed that emotional symptoms were more in girl than boys. In contrast, the conduct problems were more in boys than girls. Anxiety and Depression was more in adolescents than children
Concussion: Our study showed obesity has a negative effect on the anxiety, depression, and self-esteem of children and adolescents. It can be suggested that obesity might be a more important risk factor for depression, anxiety, and other psychiatry disorders. This study also emphasizes the importance of prevention of obesity.

Fragile X syndrome (FXS) is the most common cause of inherited mental retardation caused by expansion of a (CGG) repeat region up to 1000 repeat in 5' region of the FMR1 gene located in FRAXA locus Xq27.3. To better understand the mechanism involved in expansion of CGG region, the molecular characteristic of the flanking microsatellite markers in the region must be clarify in different populations. This study has aimed to examine the potential association between specific haplotype and the expanded AC-repeat region in cases and controls chromosomes.
Forty unrelated FXS males and 62 unrelated normal males originating from various regions of Iran were haplotyped by analyzing two CA-repeat markers, FRAXAC1 and DXS548.
Significant linkage disequilibrium was obtained between DXS548 and FRAXAC1 specific marker alleles and CGG repeat expansion among 40 fragile X cases compared to 62 normal controls. The frequencies of DXS548 and FRAXAC1 longer alleles in patients are significantly higher than that in control group. Two FRAXAC1 long alleles were only observed in cases, possibly due to concatenated mutations. The increase of heterozygosities in fragile X cases (DXS548 78.6%, FRAXAC1 64.6%) in comparison to the controls (DXS548 63.0%, FRAXAC1 47.0%) showed a multimodal distribution of fragile X associated alleles.
Haplotype analyses with DXS548 and FRAXAC1 markers represented that haplotype distribution in the normal controls and FXS patients were significantly different, representing a weak founder effect.

No drugs have been approved for pediatric migraine prophylaxis by the Food and Drug Administration up to now. The aim of the present research was to compare effectiveness and tolerability of melatonin and amitriptyline in pediatric migraine prevention.
In a parallel single-blinded randomized clinical trial, 5-15 year old children with diagnosis of migraine that preventive therapy was indicated in whom and were referred to Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd-Iran from June 2013 to January 2014, were randomly allocated to receive 1mg/kg amitriptyline or 0.3 mg/kg melatonin for three consecutive months.
Primary outcomes were frequency of good response (more than 50 % of reduction in monthly headache frequency) and efficacy in reduction of severity, duration and disability of headache. Secondary outcome was drugs clinical adverse events.
41 girls (51.3%) and 39 boys (48.7%) with mean age of 10.44±2.26 years were evaluated. Good response was seen in 82.5% of amitriptyline and 62%.5 of melatonin groups and amitriptyline was statistically significant more effective. (P= 0.04)
Severity, duration and Pediatric Migraine Disability Assessment score (PedMIDAS) of headache reduced with melatonin from 6.05±1.63 to 4.03±1.54 scores, from 2.06±1.18 to 1.41± 0.41 hours, and from 33.13±9.17 to 23.38±9.51 scores, respectively. Severity, duration and PedMIDAS of headache decreased with amitriptyline from 6.41±1.67to 2.25±1.21, from 2.55 ±1.85to 0.56±0.51h, and from 31.4±9.33 to 8.28 ± 3.75, respectively. (All p Amitriptyline and melatonin are effective and safe in pediatric migraine prophylaxis but amitriptyline can be considered as a more effective drug.

Parental pain catastrophizing is a construct which is recognized to have a significant impact on experience and report of pain in both children and parents. The main aim of the current research is to investigate the probable relationship of parental pain catastrophizing with the parent reports of children’s anxiety, depression and headache severity amongst Iranian parents of children with chronic or recurrent headache.
In this study 212 parents (120 mothers and 92 fathers) of children with chronic or recurrent pain participated and completed the Pain Catastrophizing Scale; Numeric Pain Rating Scale, asking for the average of pain severity in last three months before the research, and the Anxiety and Depression subscales of the Children Behavioral Check List.
Findings: The mean age of parents was 35.41 (SD= 5.58) and the mean age of children were 9.83 (SD= 2.77). A total of 72 girls and 60 boys participated in this study with a mean pain severity for headache in last three months before the research of 4.99 (SD=2.63). Probable sex differences according to pain catastrophizing, pain severity, anxiety and depression were assessed. In the next step, the predictability of pain severity from parental pain catastrophizing was evaluated. Results indicated a significant relationship in maternal pain catastrophizing and estimates of pain intensity by mothers.
These findings represent the importance of parent’s cognitive factors affecting their reports of their children’s pain and related emotional disturbances.

Determining maternal and infantile factors associated with the number of attending times of preterm infants to Neonatal Follow up and Early Intervention services during one year after discharge from neonatal intensive care unit.
This study used data from a cohort of preterm infants born in Arash Women’s Hospital and consecutively admitted to the NICU at the same hospital from April 2014 to February 2015.
Data was gathered by completing a questionnaire administered via phone. Data included mother’s age, education, type of pregnancy, history of abortion, history of premature birth, self-reported post-partum depression and the number of children, as well as infant’s gender, birth weight, gestational age, length of stay in the NICU, living area, twin or triplet birth, number of siblings, and the child rank. Number of attending times to services was recorded.
After multivariate analysis, shorter length of stay in the NICU, lower maternal education, more number of children, self-declared lack of awareness about Neonatal Follow up and Early Intervention services, and self-reported lack of referral by a physician were the only factors that continued to be significantly correlated, and in fact, the truly influential ones associated with number of attending times.
Results of this study have defined some predictors of poor follow up and early intervention service utilization in a high-risk group of infants following NICU discharge, which is suggested to be addressed by policymakers to overcome possible barriers to attendance.

Poor bone health with related morbidity is a major problem with Duchene Muscular Dystrophy (DMD). Decreased mobility and long-term corticosteroid therapy are involved in poor bone health in DMD. This study investigates bone mineral density and bone metabolism in 30 steroid treated DMD patients and also comparison of mentioned factors between ambulated and non-ambulated patients.
In this cross-sectional study 30 boys (21 patients ambulate and 9 non-ambulate) with documented DMD, according to genetic analysis, were enrolled. Demographic characteristics, neurologic exam findings, muscle function score, corticosteroid dose and duration and food frequency questionnaire were recorded. Bone mineral density was measured with dual- energy X-ray absorptiometry (DEXA) on lumbar spine and left proximal femur. Serum 25-hydroxyvitamin D, calcium, phosphorus and parathyroid hormone (PTH) levels were measured.
Osteoporosis was found in 86.7% patients. Mean bone density in the lumbar spine was -1.5±0.24 and -1.4±0.27 in ambulates and non-ambulates respectively (P=0.7). Mean bone density at proximal femur was -3.4±0.2 in ambulates and -3.4±0.3 in non-ambulates (p =0.48).
Intra-groups statistical analysis showed significant difference between bone mineral density at lumbar spine and proximal femur in both mentioned groups (P High prevalence of vitamin D deficiency and osteoporosis was found in DMD patients although osteoporosis severity was not affected by muscle function and ambulation. So it seems that vitamin D supplementation can improve vitamin D status and osteoporosis in these patients, especially in non-ambulates.

Here we report a 5-month-old boy with thiamine Responsive Megaloblastic Anemia syndrome (TRMA syndrome) with several attacks of stroke. In addition to the cardinal clinical manifestations of the syndrome (thiamine-responsive megaloblastic anemia, diabetes mellitus, and sensor neural hearing loss), the patient showed the ischemic attack of stroke. Megaloblastic anemia and Diabetes were diagnosed at 8 months and was successfully treated with vitamin and insulin prescription. After treatment of thiamine diabetes was controlled and insulin was discontinued. In spite of the thiamine administration, the second stroke as hemorrhagic stroke was occurred in the patient after a few months. TRAMA is inherited in an autosomal recessive manner. TRMA was confirmed by mutation in SLC19A2. A homozygous splice site variant was detected in SLC19A2 gene. According to our knowledge stroke was not reported in this syndrome (only in one report about one attack in an adult patient) but in this patient several attacks of stroke was report before and after thiamin administration.

Moyamoya disease is a chronic progressive vascular disease of brain has been characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis with prominent arterial collateral circulation. We introduce a patient with Moyamoya that was been misdiagnosed.
We report a 16-year-old female from northeast of Iran who complained left hemiparesis and was diagnosed Moyamoya disease by brain and cervical CT-Angiography.
There is still great difficulty in the diagnosis of diffuse white matter lesions and our case shows that moyamoya disease should be considered in differential diagnoses especially among young patients presenting with unexplained cerebrovascular syndromes. The CT-Angiography showed bilateral internal carotid stenosis with "puff of smoke" collateralization arising from the circle of Willis, therefore Moyamoya disease was raised.The clinical diagnosis of Moyamoya is challenging and misdiagnosis is probable. Therefore, the physicians should know this disease and think about it in patients with Juvenile stroke.

Reciprocal balanced translocations associated with clinical features are very rare. This study reports cytogenetic and molecular cytogenetic findings in a 3-year-old patient with mild developmental retardation, slight hypotone with a de novo balanced 46, XX, t(2; 11) (q33; q23) translocation. G-banded chromosomes and FISH-Analysis were used to examine the patient's karyotype as well as her parents'. FISH-probes prepared with specific RP11-BAC clones mapped near 2q33 and 11q23 regions were used to characterize the location of the breakpoints. The FISH results revealed that one of the break points is located within the human NBEAL1-Gene locus on chromosome 2, suggesting a correlation between this gene disruption and the patient’s mild developmental retardation.

Prolonged use of topical corticosteroids, particularly in infants, albeit rare, may lead to Cushing's syndrome. Central nervous system abnormalities including brain atrophy and delayed myelination on cranial magnetic resonance imaging has been reported in patients with corticosteroid treatment. We herein report a 5-month-old female infant with brain atrophy and myelination delay that might be due to iatrogenic Cushing's syndrome caused by topical corticosteroid use.

Spinal muscular atrophy (SMAs) is a group of rare autosomal recessive diseases in which there is degeneration of alpha motor neurons in the spinal cord leading to progressive distal motor weakness. Here we report a case of type 0 SMA in newborn with generalized osteopenia and bony deformity in form of unilateral club foot. It may be emphasized that diagnosis of SMA should be kept in mind as a differential in cases of unexplained severe generalized hypotonia and severe respiratory compromise immediately after birth.