Genotype-Phenotype Analysis of Children with Epilepsy Referred for Whole-Exome Sequencing at a Tertiary Care University Hospital.

BACKGROUND: Despite the high consanguinity rates, data on genetic epilepsy in Saudi Arabia is limited. The objective of the current study was to characterize genetic mutations associated with epilepsy in pediatric patients and describe their phenotypic presentations. METHODS: A retrospective chart review was conducted among children presented with epilepsy in one center in Saudi Arabia between 2015 and 2018. Only those who had undergone genetic testing were included. RESULTS: A total of 45 patients had positive whole-exome sequencing (WES) genetic testing with 37 mutations. Six mutations (SCN1A, DENND5A, KCNQ2, ACY1, SCN2A, and PCDH19) were repeated in 15 patients, with largely heterogeneous phenotypic presentations in patients with the same mutation. Several mutations are reported for the first time in Saudi Arabia. The median age at epilepsy onset was four months. Consanguineous parents and family history of epilepsy were frequent (31.8% and 33.3%, respectively). Developmental delay (44.4%), cognitive delay (42.2%), language delay (40.0%), behavioral features (28.9%), and microcephaly (20.0%) were frequent presentations. At initial diagnosis, 68.9% of EEG and 48.9% of brain MRI were abnormal. The most currently used antiseizure medications (ASMs) were levetiracetam (48.9%), topiramate (28.9%), and valproic acid (20.0%). Approximately 60% of the patients were controlled with (47.6%) or without (11.9%) ASMs, and three (7.1%) patients died. CONCLUSIONS: Multiple mutations among children with epilepsy are reported in one hospital in Saudi Arabia, with the majority reported for the first time. The current findings highlight the importance of doing genetic testing for the evaluation of childhood epilepsy.

Syncopal attacks in children: Is it cardiac or epilepsy related?

BACKGROUND: Transient loss of consciousness (TLOC) may be mistaken for other disorders like epilepsy. Our objectives were to identify symptoms that could help differentiate epilepsy from syncope among children with TLOC and to validate previously suggested criteria. METHODS: We retrospectively reviewed the charts of patients aged 18 years or younger who presented with TLOC attacks from January 2008 to December 2018 at King Saud University Medical City, Riyadh, Saudi Arabia. Symptoms from which epilepsy and syncope could be predicted with high accuracy were included in the previously suggested criteria. The discriminative abilities of current and previous criteria were examined in receiver-operating characteristic analyses. RESULTS: Data from 46 patients, 32 with confirmed epilepsy and 14 with syncope, were included in this analysis. The mean age was 12.1 years (S.D., 4.3 years), and 60.9% of the patients were girls. According to our proposed criteria, the sensitivity, specificity, and accuracy of symptoms in predicting epilepsy were 68.8%, 85.7%, and 73.9%, respectively, and the area under the curve was 0.814 (confidence interval 0.686 to 0.941, P = 0.001). According to previously suggested criteria, the sensitivity, specificity, and accuracy of symptoms in predicting epilepsy were 63.2%, 62.5%, and 63.0%, respectively, and the area under the curve was 0.730 (confidence interval 0.541 to 0.92, P = 0.063). CONCLUSIONS: A number of self-reported/observed symptoms can be used to distinguish epilepsy from syncope with high discriminative ability. The current findings still need to be validated in larger, preferably multiple populations before they can be safely relied upon.

The impact of vitamin D food fortification and health outcomes in children: a systematic review and meta-regression.

OBJECTIVE: Vitamin D (vitD) deficiency is a global childhood health problem. Food fortification is a promising strategy to curb vitD deficiency. We aimed to assess the effectiveness of utilizing vitD fortification in staple foods to improve 25hydroxyvitamin D (25(OH)D) concentration and to reduce the prevalence of vitD deficiency among healthy children. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of vitD fortified food products compared to no fortification among healthy children aged 1-18 years old. We searched Medline, Embase, Global Health, and Cochrane (CENTRAL) databases from database inception until May 2019. Independently, six reviewers in pairs screened titles and abstracts, assessed the full text for eligibility, and performed data extraction and quality assessment. The primary outcome is the impact of fortification on 25(OH)D concentration. The secondary outcomes included the impact of fortification on the prevalence of vitD deficiency, school performance, cognitive function, school absences, infection rate, hospital admission length, and compliance with fortified food product consumption. RESULTS: We identified 2229 articles. After assessing eligibility, 20 RCTs met the inclusion criteria. The eligible RCTs assessed the fortification of milk, cereal, juice, bread, yogurt, and cheese compared with no fortification. All RCTs, except for three, had a low risk of bias. Food fortification improved 25(OH)D concentration by a mean difference (MD) of 15.51 nmol/L (95% confidence interval (CI) 6.28, 24.74; I2 = 99%), which resulted in a mean increase of 3 nmol/l for every 100 IU of vitD, when adjusted for baseline 25(OH)D concentration and country latitude. Additionally, the prevalence of vitD deficiency decreased by a risk ratio of 0.53 (95% CI 0.41, 0.69; I2 = 95%), and cognitive function improved by a MD of 1.22 intelligence quotient (IQ) points (95% CI 0.65, 1.79; I2 = 0%). The overall evidence quality was high. CONCLUSION: VitD food fortification is an effective way to improve 25(OH)D concentration, prevent vitD deficiency, and improve IQ levels. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017057631.

Validity and feasibility of the Arabic version of distress thermometer for Saudi cancer patients.

BACKGROUND: The distress thermometer (DT) has been studied and validated as an effective screening instrument for identifying distress among cancer patients worldwide. This study aims to evaluate the validity of the Arabic version of the DT in Saudi cancer patients, to define the optimal cutoff point of the Arabic DT for detecting clinically significant distress and to determine whether there is any correlation between clinically significant distress and other demographic and Problem List variables. METHODS: The original form of the DT was translated to Arabic using a forward and backward translation method. Then, a group of 247 cancer patients who were followed up at the Outpatient Oncology Clinic at King Saud Medical City in Riyadh, Saudi Arabia, completed a socio-demographic and clinical status questionnaire, the DT and the Problem List scale, and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Receiver operating characteristic (ROC) curve analyses picked out an area under the curve of 0.76 when compared with a HADS cutoff score of 15. The DT had the best sensitivity (0.70) and specificity (0.63) with cutoff score of 4. A DT score of 4 or more was found to have a statistically significant correlation with female gender, advanced cancer stages and most of the Problem List items, including child care, work or school, treatment decision, dealing with children and partners, depression, fears, nervousness, sadness, loss of interest in usual activity, religious concerns, appearance, bathing/dressing, breathing, diarrhea, fatigue, feeling swollen, fever, getting around, indigestion, memory and concentration, nausea, dry nose, pain, and sexual problems. In contrast, a multivariate regression analysis confirmed only advanced cancer stages, treatment decision, depression, fear, sadness, worry, breathing, feeling swollen, fever, indigestion, memory and concentration, dry nose and congestion, pain and sleep as independent factors associated with distress in cancer patients. CONCLUSIONS: We found the Arabic version of the DT to be a valid instrument for screening distress in Saudi patients with cancer. Our study proposes using a cutoff score of 4 as an indicator of clinically significant distress in this population.

A journey from being preterm to pediatric neurology.

This article highlights the story of two pediatric neurology residents (identical twin sisters Rana and Rawan) who work at the Division of Pediatric Neurology, Department of Pediatrics, College of Medicine and King Khalid University Hospital (KKUH), King Saud University, Riyadh, Saudi Arabia. They were born in October 1990 in the same hospital (KKUH), following preterm delivery at 33 weeks. Their birth weight was 2,000 and 1,900 g, respectively. They were admitted to the Neonatal Intensive Care Unit (NICU) at KKUH for 2 weeks. Enduring prolonged struggles due to respiratory related conditions and frequent visits to the Emergency Room during their childhood, they excelled in school graduating with high honors throughout elementary, intermediate, and secondary schools. They joined the College of Medicine, KKUH and graduated with the highest distinction (summa cum laude), and were chosen to join the Saudi Board of Pediatric Neurology Residency Program at KKUH. Their story was revealed, while they were doing a round at the same NICU, where they were once cared for 28 years earlier.