Genetic landscape of epilepsies in Kingdom of Saudi Arabia: a brief review

Epilepsy is a common chronic neurological problem with a prevalence rate of 6.5 per 1,000 in Saudi Arabia. In the field of epilepsy genetics, the rapid pace of gene discovery has resulted in exciting advances. Clinical testing using comprehensive gene panels, exomes, or genomes is becoming more widely available, resulting in a higher diagnostic yield in early-onset epilepsies and enabling precision medicine approaches. The genetic screening techniques include comparative genomic hybridization, single-gene testing, chromosomal analysis, epilepsy panel testing, whole-exome sequencing (WES), and whole-genome sequencing. It is essential to know the classification of genetic epilepsies to choose the appropriate genetic test for its differential diagnosis. Although there have been various classifications reported by different groups, the most acceptable one is to classify them based on type of epilepsy, type of gene involvement, and age of onset of epilepsy. The diagnosis of genetic epilepsies helps the treating physician determine the prognosis, select the appropriate medications, and avoid certain medications that may exacerbate epilepsy. In Saudi Arabia, recently genetic tests have been made available in many centers. Various research groups have discovered and reported a wide range of genes, especially pediatric neurologists, geneticists, and neurogenetics across the Kingdom. The availability of WES due to its cost-effective nature is another reason for the advancement in epilepsy screening in the Kingdom. The present review aims to discuss the genetic testing of epilepsy, classification of genetic epilepsies, epilepsy genetics in Saudi Arabia, and the future of epilepsy genetics in Saudi Arabia. [JBCGenetics 2022; 5(1.000): 12-16

Familial Hemiplegic Migraine with Prolonged Coma and Hyperthermia: ATP1A2 Gene Mutation Case Report in a Single Saudi Family.

Background: Familial hemiplegic migraine (FHM) is a rare disorder presented commonly with coma, hyperthermia, and headache. FHM is usually associated with fully reversible motor weakness as a specific symptom of aura. Seizure and fever are the secondary features observed. All the affected individuals were subjected to several laboratory tests. Case presentation: Three sisters diagnosed with type 2 familial hemiplegic migraines presenting features such as coma and hyperthermia. The brain (MRI) revealed focal subtle cortical swelling, Electroencephalography (EEG) showed unilateral slowing, while no signs of infectious disease were observed. Molecular and genetic tests using whole exome sequencing (WES) identified a novel heterozygous mutation (c.2450T>A p.Ile817Asn) in the exon 18 of the ATP1A2 gene (NM_000702.3). The variant segregated with the disease phenotype within the family. Conclusion: The current study report for the first time, a Saudi family with migraine coma having a novel heterozygous AT1A2 mutation. [JBCGenetics 2019; 2(1.000): 85-90

Puberty Onset among Boys in Riyadh, Saudi Arabia

Background The ages of onset of pubertal characteristics are influenced by genetic, geographic, dietary and socioeconomic factors; however, due to lack of country-specific norms, clinicians in Saudi Arabia use Western estimates as standards of reference for local children. Aims The aim of the Riyadh Puberty Study was to provide data on pubertal development to determine the average age of onset of pubertal characteristics among Saudi boys. Methods Cross-sectional study among male school children in Riyadh, Saudi Arabia, in 2006, 542 schoolboys, aged 6 to 16 years old, from diverse socioeconomic levels were selected into the sample using a cluster sample design. Tanner stages were ascertained during physical examination by pediatric endocrine consultants, and also trained pediatric residents and fellows. Results The mean age (standard deviation) at Tanner Stages 2, 3, 4, and 5 for pubic hair development of Saudi boys was 11.4 (1.6), 13.3 (1.3), 14.4 (1.0) and 15.1 (0.8) years old, respectively. For gonadal development, the mean age (standard deviation) at stages 2, 3, 4, and 5 were 11.4 (1.5), 13.3 (1.2), 14.3 (1.1) and 15.0 (0.9) years old, respectively. Conclusion The ages of onset of pubertal characteristics, based on gonadal development, among Saudi boys are comparable to those reported in Western populations

Epidemiology and outcomes of neurofibromatosis type 1 (NF-1): multicenter tertiary experience

Purpose: The aim of this manuscript was to assess the epidemiology and clinical features of Neurofibromatosis type 1 (NF-1) based on the newly published revised NF-1 diagnostic criteria and to evaluate complications of NF-1 including neurodevelopmental disorders. Patients and methods: A retrospective cross-sectional observational study was conducted in the Ministry of National Guard Health Affairs (MNGHA) healthcare organization branches including four tertiary hospitals and 51 primary health care centers in different regions in Saudi Arabia. This study included all patients diagnosed with NF1 using the revised NIH diagnostic criteria published in 2021 that were registered at the electronic medical records (EMR) from 2015 to 2021. Results: A total of 184 patients fulfilled the diagnostic criteria and were included in this study. The median age at diagnosis was 11 years (IQR: 4.00-20.25). The most encountered diagnostic criteria in this study were Café-au-lait macules (85.3%), and (42.9%) were found to have two or more neurofibromas with plexiform neurofibroma being the most common subtype (23.36%), approximately (36.4%) of the patient with optic pathway glioma. Nearby (26.6%) of the patients displayed different type of tumors. Iris Lisch nodules were presented in 36.4% of patients at a median age of 12 years (IQR: 9.0-21.8). Cardiovascular abnormality was encountered in 9.8% of the patients. Around 27.7% of the patients reported headache and 11.4% of the patient suffered from different type of epilepsy. Besides, 10.5% of the patients had intellectual disability, 33.8% suffered from communication disorders, and 4.9% patients had ADHD. Conclusion: The results of this study will enable practitioners to adopt a more holistic approach and prioritize numerous attributes, which they can subsequently incorporate into their therapeutic methodologies. Furthermore, the identification of these attributes will facilitate an expeditious and accurate diagnosis. Hence, the implementation of intervention during its nascent phase may result in a more advantageous consequence.</p

Adapting evidence-based clinical practice guidelines for people with attention deficit hyperactivity disorder in Saudi Arabia: process and outputs of a national initiative

Abstract Background We recently adapted the published National Institute for Health and Care Excellence (NICE) Attention deficit hyperactivity disorder (ADHD) diagnosis and management guideline to the Saudi Arabian context. It has been postulated that adaptation of evidence-based clinical practice guidelines to the local healthcare context rather than de-novo development will improve their adoption and implementation without imposing a significant burden on resources. The objective of this paper is to describe the adaptation process methodology utilized for the generation of the first national guideline for management of people with ADHD in Saudi Arabia. Methods We used the KSU-Modified-ADAPTE methodology for the guideline adaptation process. We describe the full process in detail including the three phases of set-up, adaptation, and finalization. The process was conducted by a multidisciplinary guideline adaptation group in addition to an external review for the clinical content and methodology. Results The group adapted ten main categories of recommendations from one source CPG (NICE). The recommendations include: (i) service organisation and training, (ii) recognition, identification and referral, (iii) diagnosis, (iv) support, (v) managing ADHD, (vi) dietary advice, (vii) medication, (viii) maintenance and monitoring, (ix) adherence to treatment, and (x) review of medication and discontinuation. Several implementation tools were compiled and developed to enhance implementability including a clinical algorithm, quality measures, coding system, medication tables, translations, patient information, and online resources. Conclusions The finalized clinical practice guideline provides healthcare providers with applicable evidence-based guidance for the management of people with ADHD in Saudi Arabia. The project also demonstrated the effectiveness of KSU-Modified-ADAPTE, and emphasized the value of a collaborative clinical and methodological expert group for adaptation of national guidelines.http://deepblue.lib.umich.edu/bitstream/2027.42/173676/1/13034_2020_Article_351.pd