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Objectives: Hyperinsulinism refers to improper insulin secretion in the presence of low plasma glucose, causing severe and persistent hypoglycemia in infants and children. The brain's occipital lobe, which includes the visual and plays an essential role in visual perception is specifically sensitive to hypoglycemia-induced damage. The present study aims to investigate the visual perception in children suffering from hyperinsulinism and to compare it with the control group., Materials & Methods: This cross-sectional control study, conducted in 2020 in Isfahan, Iran, involved 20 children aged 4-13 years with hyperinsulinism and 20 healthy children of the same age and gender for comparison. In both groups, the measuring instrument was the Test of Visual Perceptual Skills (non-motor) Third Edition., Results: The mean visual perceptual quotient in the case and control groups was 80.50±26.74 and 116.50±7.56 (p-value<0.001), respectively. The results overall indicated that children suffering from hyperinsulinism were weaker than healthy children in all areas of visual perception., Conclusion: Based on the obtained results, it is recommended that children suffering from hyperinsulinism be screened regarding visual perceptual disorders since this screening may be helpful in initiating different rehabilitation programs among these patients., Competing Interests: None declared, (© 2023 The Authors.)

Background: Paroxysmal hemicrania (PH) is a severe short-lasting headache usually localized around the eye. It might occur in conjunction with ipsilateral autonomic manifestations of trigeminal nerve stimulation. PH responds well to indomethacin treatment; however, considering the adverse effects of indomethacin, its long-term use is a matter of question and investigations about other prophylactic medications are going on, but they are inconclusive. The current study aims to investigate the efficacy of prophylactic use of cyproheptadine to control PH symptoms., Materials and Methods: The current clinical trial was conducted on 20 children diagnosed with PH undergoing prophylactic treatment with cyproheptadine syrup at a dosage of 0.2-0.4 mg/kg twice daily for a period of 3 months. The duration, frequency, and severity of headaches were assessed at baseline and then monthly for 3 months., Results: Significantly shorter duration, less frequency, and less severity of headaches were observed in the postintervention assessments of the patients ( P < 0.001). The effect size analysis showed that the greatest effect of the treatment was on the intensity of the headache (effect size: 0.866) and the least effect was on duration of the headache (effect size: 0.775). Drowsiness (5%) and increased appetite (30%) were the only adverse effects of treatment with cyproheptadine., Conclusion: Findings of this study showed that short-term prophylactic cyproheptadine in divided doses of 0.2-0.4 mg/kg could appropriately improve PH in terms of frequency, duration, and the intensity of the attacks. Nevertheless, further investigations are strongly recommended., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Advanced Biomedical Research.)

Due to low amounts of withanolides produced in some plants and high demand for various applications, their biotechnological production is widely researched. The effects of two explant types (i.e., leaf and stem from the in vitro seedlings of three genotypes of Withania somnifera) and four Rhizobium strains (i.e., LBA 9402, A4, ATCC 15834, and C58C1) to improve hairy root formation efficiency was studied. Furthermore, the combined effects of β-cyclodextrin (β-CD) and methyl jasmonate (MeJA) on withaferin A production after 48 h exposure time was examined. Four hairy roots having the maximum percentage of induced roots and mean number of induced roots to analyze their growth kinetics and identified G3/ATCC/LEAF culture having the maximum specific growth rate (μ = 0.036 day -1 ) and growth index (GI = 9.18), and the shortest doubling time (T d  = 18.82 day) were selected. After 48 h exposure of G3/ATCC/LEAF culture to different elicitation conditions, maximum amounts of withaferin A were produced in samples co-treated with 0.5 mM β-CD + 100 μM MeJA (9.57 mg/g DW) and 5.0 mM β-CD + 100 μM MeJA (17.45 mg/g DW). These outcomes represented a 6.8-fold and 12.5-fold increase, respectively, compared to the control. Similarly, combined β-CD/MeJA elicitation increased gene expression levels of HMGR, SQS, SMT-1, and SDS/CYP710A involved in withanolides biosynthetic pathway, of which just SMT-1 had significant correlation with withaferin A production. These results demonstrated the superiority of G1-leaf explant and ATCC 15834 for hairy root induction, and revealed synergistic effect of MeJA and β-CD on withaferin A production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Aim and Objective: Intellectual disability (ID) is a heterogeneous condition affecting brain development, function, and/or structure. The X-linked mode of inheritance of ID (X-linked intellectual disability; XLID) has a prevalence of 1 out of 600 to 1000 males. In the last decades, exome sequencing technology has revolutionized the process of disease-causing gene discovery in XLIDs. Nevertheless, so many of them still remain with unknown etiology. This study investigated four families with severe XLID to identify deleterious variants for possible diagnostics and prevention aims., Methods: Nine male patients belonging to four pedigrees were included in this study. The patients were studied genetically for Fragile X syndrome, followed by whole exome sequencing and analysis of intellectual disability-related genes variants. Sanger sequencing, co-segregation analysis, structural modeling, and in silico analysis were done to verify the causative variants. In addition, we collected data from previous studies to compare and situate our work with existing knowledge., Results: In three of four families, novel deleterious variants have been identified in three different genes, including ZDHHC9 (p. Leu189Pro), ATP2B3 (p. Asp847Glu), and GLRA2 (p. Arg350Cys) and also with new clinical features and in another one family, a reported pathogenic variant in the L1CAM (p. Glu309Lys) gene has been identified related to new clinical findings., Conclusion: The current study's findings expand the existing knowledge of variants of the genes implicated in XLID and broaden the spectrum of phenotypes associated with the related conditions. The data have implications for genetic diagnosis and counseling., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Sickleweed (Falcaria vulgaris) is the name of a species of annual, and perennial herbaceous plants of the genus Falcaria. Climate change could negatively influnces the performance of various plant species in plant kingdom. In this study, 15 different sickleweed populations from seven provinces of the country were collected based on an unbalanced nest design with 10 replications and the percentage of essential oil, types of chlorophyll, phenol, proline, protein, and carotenoids were measured on them. The results showed that there was a significant difference between populations at the level of one percent for the studied traits. The results of the mean comparison showed that populations Ard-Shaban and Qaz-Ilan in terms of the evaluated traits and especially the percentage of essential oil were at the upper of the studied samples and selected as suitable populations. In addition, populations Gilan-Deylaman and Kur-Gerger-e Sofla were also identified as superior populations in terms of studied traits by cluster analysis and principle component analysis (PCA). Since the high level of proline and biochemical and physiological traits in plants can play a role in plants' tolerance to stresses, therefore, populations with high values of these traits can be used in stress tolerance breeding programs. Therefore, in this study, populations Gilan-Deylaman and Kur-Gerger-e Sofla can be suitable populations for this purpose. In addition, the essential oil of this plant is used in the treatment of diseases, and therefore populations Ard-Shaban and Qaz-Ilan, which showed a high percentage of essential oil, can be used in breeding programs to increase the performance of this trait., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rahimi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Epilepsy, the tendency to have recurrent unprovoked seizures, is the most common chronic neurological disorder worldwide. About 20% to 40% of children with epilepsy suffer from refractory seizures, causing neurological, cognitive, and psychosocial impairments. Identifying the factors contributing to pediatric refractory seizures can help neurologists effectively prevent, diagnose, and treat their patients., Materials & Methods: In this cross-sectional study, 2 to 16 years old children with refractory seizures (drug-resistant epilepsy) were assessed regarding their demographic and seizure-associated characteristics., Results: Children with refractory seizures had a significantly higher rate of neonatal asphyxia, hospitalization after birth, neonatal seizures, and seizure in the first year of life, history of infantile spasm, and symptomatic epilepsy. Furthermore, polymorphic seizures and brain MRI abnormalities were significantly more frequent among them. Several different mechanisms have been suggested for explaining intractability in epileptic patients. None of the mechanisms can explain all patients. The most common underlying etiologies for seizures in the intractable group were hypoxic-ischemic damage, cerebral dysgenesis, and genetic disorders., Conclusion: Seizure intractability results from a tremendous deleterious change in the brain's structure. Early identification of the risk factors and prediction of patients likely to have pharmaco-resistant epilepsy will allow more aggressive treatment and earlier specialized intervention., Competing Interests: None

Objective: Epilepsy is a chronic neurological disorder that affects 0.5%-1% of children. 30%-40% of patients are resistant to current anti-epileptic drugs. Lacosamide (LCM) appeared to be effective, safe, and well tolerated in children and adolescents. This study was aimed to evaluate whether LCM could be an effective add-on therapy in children with refractory focal epilepsies., Methods: This study was conducted from April 2020 to April 2021 in Imam Hossein Children Hospital, Isfahan, Iran. We included 44 children aged 6 months to 16 years with refractory focal epilepsy (based on International League Against Epilepsy criteria). LCM was given in divided doses of 2 mg/kg/day, increasing by 2 mg/kg every week. The first follow-up visit was 6 weeks later, when all patients had reached the therapeutic dose., Findings: The average age of the patients was 89.9 months. 72.5% of children had focal motor seizures. Evaluation of percent change in seizure frequency and duration before and after treatment showed a 53.22% reduction in seizure frequency and 43.72% reduction in seizure duration after treatment. Our study group tolerated LCM well, with few side effects. Headache, dizziness, and nausea were common side effects. In line with other studies, none of the suspected risk factors could predict response to LCM treatment., Conclusion: LCM appears to be an effective, safe, and well-tolerated medication in children with uncontrolled drug-resistant focal epilepsy., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Research in Pharmacy Practice.)

Objective: This study aimed to find the common inborn errors of metabolism in Iranian patients with autism spectrum disorder., Methods: In this cross-sectional multicenter study, 105 children and adolescents with autism spectrum disorder from six centers in different cities of Iran were enrolled between August, 2019 and October, 2020. Metabolic screening, including measuring plasma levels of amino acids, acylcarnitines, creatine, and guani-dinoacetate, and urinary levels of organic acids, purines, and pyrimidines was performed. Other data, including age, parental consanguinity, history of seizure, developmental mile-stones, and physical examination, were also recorded., Results: An inborn error of metabolism was found in 13 (12.4%) patients. Five patients (4.8%) had cerebral creatine deficiency syndrome, 4 (3.8%) had arginine succinate aciduria, 2- methylbutyryl glycinuria, short-chain acyl-CoA dehydrogenase deficiency, and combined methylmalonic aciduria/malonic aciduria. There was a strong association between positive meta-bolic evaluation and parental consanguinity, history of seizures, microcephaly, and delayed development., Conclusions: Our results suggest that metabolic screening should be performed in the cases of autism associated with parental consanguinity, developmental delay, and a history of seizures. The assays to be considered as a screening panel include plasma or blood amino acids, acylcarnitines, creatine and guanidinoacetate, and urinary levels of organic acids.

Background: Insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined., Objective: To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA)., Methods: IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project., Results: By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with lower copy numbers of SMN2. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease., Conclusions: The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

Background: Migraine, one of the most common headaches in children, has a significant impact on children and their family's quality of life (QoL). There are two approaches for controlling migraine headaches preventative and controlling acute attacks. Several drugs have been used for this purpose, and tricyclic antidepressants were at the top. Amitriptyline has shown not only a desirable effect on controlling the headaches but also some adverse side effects. Recently, finding effective drugs with fewer side effects, become more critical. Among them, nutraceuticals were one of the promising ones., Materials and Methods: In this randomized clinical trial on 72 patients aged 5-15 years old with diagnosis of migraine based on the International Headache Society criteria, we compare the effectiveness of coenzyme Qten on frequency, duration, and severity of childhood migraine. For comparing the QoL, we used the International PedMIDAS questionnaire., Results: Coenzyme Qten showed good therapeutic effects in children, especially in long-term use; however, amitriptyline showed more rapid response. After 3 months of treatment, clinical outcomes in the two groups did not significantly differ from each other. Similarly, Children's QoL increased in the same way. There are more reported side effects in children using amitriptyline compared to coenzyme Qten., Conclusions: According to results, Co-enzyme Q10, with fewer side effects and comparable therapeutic effects, especially in the long term, could be a good drug for prophylactic treatment of migraine headaches., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Advanced Biomedical Research.)

Background: We aimed to compare the effectiveness of Levetiracetam and Piracetam on the severity and frequency of spells in children with severe breath-holding spells (BHS), i.e. bening, paroxysmal, and nonepileptic events that are common in early childhood., Materials and Methods: This study is a randomized controlled clinical trial in 71 children from 6 months to 6 years of age with BHS. They were randomly assigned to the two study groups (Levetiracetam and Piracetam group). The frequency and severity of BHS and the response to treatment were recorded on monthly visits during our 3 months follow-up., Results: There was a significant decline in the average number of frequency of spells before and after 3 months of treatment in each group in this study. Levetiracetam had significant effects on the average incidence of the loss of consciousness and seizure-like movements in our study, while Piracetam had no significant effect on the loss of consciousness. Our result showed better response in the Levetiracetam group (88.9% partial or complete response after treatment) compared with the Piracetam group (77.1% partial or complete response after treatment); however, it was not significant. It seems that Levetiracetam had better effect than Piracetam in some aspects in the treatment of BHS., Conclusions: Both Piracetam and Levetiracetam are safe and had significant effects on the frequency of BHS in our study, however, levetiracetam showed superior effects on the severity of BHS., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Advanced Biomedical Research.)

Objective: This study was conducted to evaluate the validity of performing whole exome sequencing in children with unexplained intellectual disability (ID), developmental delay (DD), and epilepsy., Methods: We enrolled 61 Iranian children with unexplained DD/ID, and epilepsy with no etiologic diagnosis. 64 % of cases were male and 36 % were female, with a mean age of 6.2 years (range, 38 days to 15 years). Approximately 79 % of patients were born to consanguineous parents or had non-related parents from a highly inbred local region. Whole-exome sequencing analysis followed by Sanger sequencing was performed in all patients., Results: Pathogenic/likely pathogenic variants were identified in 59% (36/61) of patients, consisting of 26 novel and 14 known alterations. Variants of unknown significance were observed in 6.5 % (4/61) of patients. Variants in 28 genes have not been previously reported in Iranian patients with ID. Several additional phenotypes, mostly microcephaly, were common in 57.4 % of cases. Additionally, epilepsy was refractory in 40 % of patients. Three groups of brain anomalies consisting of brain dysgenesis, brain atrophy, and leukodystrophy were identified in our cohort. Mutations in genes implicated in cellular metabolic pathways were the most common, followed by ion channel/ion transporter and transcription pathways., Discussion: High-throughput DNA sequencing of the Iranian population with a high rate of parental consanguinity is a valuable strategy for identifying genetic etiology in children with unexplained ID/DD and epilepsy. Determining the genetic basis and most commonly involved pathways may help to identify novel genes and targeted antiepileptic treatments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they have an identical pathological variant and/or belong to the same family. Herein, we reported two male siblings with ID in an Iranian family. By means of the whole-exome sequencing method, elder brother affected by a moderate form of ID exhibited a de novo missense variant in the KCNQ3 gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in the UBE3A gene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in the KCNQ3 gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals with KCNQ3-related developmental delay show de novo variants in the KCNQ3 gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum of KCNQ3 pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis.

Objective: Benign enlargement of the subarachnoid space (BESS) is the most common cause of macrocephaly in infants. This study aimed to evaluate the neurodevelopmental outcomes in infants with BESS., Materials & Methods: In this follow-up study, all records of infants diagnosed with BESS in 2012-2016 were assessed. A clinical follow-up examination was carried out at 6, 12, 18, and 24 months of age to assess the macrocephaly outcomes. Denver Developmental Screening Test-II (DDST-II) was used for evaluating the psychomotor development of infants at 24 months of age. All data were entered in SPSS Version 13, and descriptive statistics were measured., Results: Out of 32 infants included in this study, 28 (87.5%) were boys. Five cases of prematurity history (15.6%), and 23 cases of macrocephaly in the family (71.9%) were recorded. The mean age of BESS diagnosis was 6.8 months (SD=3.2). subdural hematoma was reported in one infant (3.1%). Also, 28 infants showed macrocephaly at 18 months of age (83.3%). Seven patients had developmental delay, according to DDST-II (22%). The mean head circumference at birth and six months of age was significantly greater in infants with developmental delay compared to those with normal development. There was a significant difference between the mean head circumference at birth (P=0.05) and the mean head circumference at six months of age (P=0.02)., Conclusion: Developmental delay is frequent in BESS infants, especially those with macrocephaly at birth and six months of age, and requires medical attention., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 The Authors. Published by Shahid Beheshti University of Medical Sciences.)

Variation in metabolism and partitioning of carbohydrates, particularly fructans, between annual and perennial Cichorium species remains a challenging topic. To address this problem, an annual (endive, Cichorium endive L. var. Crispum; Asteraceae) and a biennial species (chicory, Cichorium intybus L. var. Witloof; Asteraceae) were compared with in terms of variability in carbohydrate accumulation and expression patterns of fructan-active enzyme genes, as well as sucrose metabolism at various growth and developmental stages. In general, constituents such as 1-kestose, nystose, and inulin were detected only in the root of chicory and were not present in any of the endive tissues. For both species, flower tissue contained maximum levels of both fructose and glucose, while for sucrose, more fluctuations were observed. On the other hand, all the genes under study exhibited variation, not only between the two species but also among different tissues at different sampling times. In endive root compared to endive leaf, the expression of cell wall invertase genes and sucrose accumulation decreased simultaneously, indicating the limited capacity of its roots to absorb sucrose, a precursor to inulin production. In addition, low expression of fructan: fructan fructosyltransferase in endive root compared to chicory root confirmed the inability of endive to inulin synthesis. Overall, annual and biennial species were different in the production of inulin, transport, remobilization, and unloading of sucrose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An environmentally benign, one-pot and highly scalable method was presented to produce biogenic silver nanoparticles (Ag NPs) using the solid-state synthetic route. Four plant-derived candidate bio-reductants ( i.e. , Datura stramonium, Papaver orientale, Mentha piperita, and Cannabis sativa ) were investigated to compare the efficiency of solid-state route and typical solution method. M. piperita was selected as the best plant resource to produce totally pure and uniform Ag NPs (average diameter of 15 nm) without any aggregation. The purity and size of biogenic Ag NPs, were tailored by adjusting the M. piperita leaf powder/silver nitrate weight ratio and temperature. The as-synthesized Ag NPs were effectively utilized as an eco-friendly nanoadsorbent in water remediation to remove a model dye (i.e., crystal violet). The key factors affecting on the sorption process (i.e., nanoadsorbent dosage, temperature, pH, dye initial concentration, and shaking time) were investigated. The pseudo-second-order kinetic model was well fitted to the sorption process and at the optimum sorption conditions, based on the Langmuir model, the adsorption capacity was found to be 704.7 mg/g. The current, cost effective and feasible method could be considered as an applicable strategy to produce green, reusable and proficient Ag NPs as nanoadsorbents for removal of dyes from contaminated water., (© 2020 The Author(s).)

Objective: This study was performed to investigate whether levetiracetam should be preferred to carbamazepine as a treatment choice for benign childhood epilepsy with centro Temporal spikes (BCECTS), the most common partial epilepsy of childhood., Methods: This randomized clinical trial study included 92 children with rolandic epilepsy aged 4-12 years referred to the Pediatric Neurology Clinic at Imam Hossein Hospital, Isfahan, Iran, from April 2019 to January 2020. Patients were selected consecutively and randomly assigned to two study groups (levetiracetam and carbamazepine groups). Patients were followed and revisited every 2 months for 6 months after starting the medication. The frequency and duration of seizure attacks and drug side effects were recorded before treatment and in bi-monthly visits. Data were analyzed by SPSS software Version 24 using Mann-Whitney U- test and Friedman test., Findings: In our study, the seizure frequency decrease was not significantly different between the two groups; however, patients in both groups showed significantly lower seizure frequency in 2, 4, and 6 months of follow-up compared to starting time. After a follow-up for 6 months, one out of 47 (2.1%) patients using levetiracetam showed intolerance, resulting in changing the medication. In addition, two out of 48 (4.1%) patients in the carbamazepine group had skin rashes. No significant changes had been reported regarding the duration of seizure attacks in both groups after treatment., Conclusion: This study showed encouraging results for using levetiracetam, with acceptable results and fewer side effects for the treatment of children with BCECTS in Iran., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Research in Pharmacy Practice.)

Background: Stuttering is a kind of speech disorder that affects about 1% of total population. As the origin of this disorder is not obviously diagnosed yet, various remedies have been practiced and among them different medicines have been studied, but unfortunately no significant effective drugs have been recognized yet. As stuttering imposes a great social and mental costs to the patients and their families, finding an effective medicine will help significantly. In this study we have focused on the effects of levetiracetam (LEV) treatment on children suffering from stuttering., Methods: In this clinical trial study, 30 children aged > 3 years (median 3.8 years) with stuttering and abnormal sleep electroencephalogram (EEG) were treated by LEV and followed-up for a minimum period of 6 weeks. The starting dose of 20 mg/kg/day was increased at an interval of 1 week by 20 mg/kg/day, if necessary, up to maximum dose of 60 mg/kg/day., Results: Overall LEV was effective in 70% of patients, decreasing stuttering to at least 50%. Three children (10%) became stuttering-free and only in one (3.3%) child an increase in stuttering was observed. There were statistically significant differences for efficacy in the presence of variables such as age groups, seizure, stuttering family history, and EEG data., Conclusions: LEV is an effective drug for treatment of childhood stuttering in those that have abnormal sleep EEG., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 International Journal of Preventive Medicine.)

Background: Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in SMN1 is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non-SMN1-related spinal muscular atrophies are caused by variants in a number of genes, including VRK1, encoding the vaccinia-related kinase 1 (VRK1). VRK1 variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly., Results: Here, we report an association of a novel homozygous splice variant in VRK1 (c.1159 + 1G>A) with childhood-onset SMA or juvenile lower motor disease with brisk tendon reflexes without pontocerebellar hypoplasia and normal intellectual ability in a family with five affected individuals. We show that the VRK1 splice variant in patients causes decreased splicing efficiency and a mRNA frameshift that escapes the nonsense-mediated decay machinery and results in a premature termination codon., Conclusions: Our findings unveil the impact of the variant on the VRK1 transcript and further support the implication of VRK1 in the pathogenesis of lower motor neuron diseases., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Background: This study aimed to investigate the clinical characteristics and neurodevelopmental outcomes of children with West syndrome (WS) by using the Bayley-III scale of infant development, as the first report from the Middle-East., Methods: Between January 2013 and February 2016, we prospectively enrolled 67 consecutive patients with a confirmed diagnosis of WS from Isfahan, Iran. Cognition, language and motor outcomes of the studied subjects were evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III)., Results: Overall, 67 cases, including 34 (50.7%) boys and 33 (49.3%) girls (a male/female ratio of 1.03), were enrolled for the study. The mean age was 26.7 ± 12.9 months. Among the subjects, 50 (74.6%) patients had symptomatic WS, and 17 (25.4%) patients had cryptogenic WS. "Severe delay" was found in 76.9% of the patients regarding cognitive evaluation, 67.7% for language and communication abilities, and, 81.5% for motor function. The patients with cryptogenic WS were significantly more likely to have more favorable outcomes in motor (p = 0.035), cognitive (p = 0.035) and receptive language (p = 0.043) in comparison to those who had symptomatic WS. The patients with controlled seizures were significantly more likely to have more favorable outcomes in motor (p = 0.027) and cognition (p = 0.011) as compared to those with uncontrolled seizures., Conclusion: WS was associated with poor neurodevelopmental outcome in our study. Severe developmental delay was associated with two major factors: (i) presence of a specific underlying abnormality (symptomatic WS) and(ii) persistent seizures as a result of the former., (Copyright © 2019 Elsevier Ltd. All rights reserved.)