Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known ...disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function.
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•Multiplex consanguineous families are rich sources for novel gene discovery•Prescreening these families for known disease genes accelerates gene discovery•33 novel candidate genes are reported in this study
Using whole-exome sequencing on prescreened multiplex consanguineous families, Alazami et al. describe the identification of 33 novel candidate genes for various neurogenetic conditions. Such families are rich sources for novel gene discovery.
Objectives:
To quantify parental acceptance of the COVID-19 vaccine and assess the vaccine hesitancy (VH) for COVID-19 vs. childhood vaccines.
Methods:
Eight vaccine hesitancy scale (VHS) items, ...adopted from WHO's Strategic Advisory Group of Immunization (SAGE), were used to assess VH for COVID-19 vaccine vs. routine childhood vaccines. We distributed the online survey to parents with the commence of the national childhood COVID-19 vaccination program in Saudi Arabia.
Results:
Among 3,167 parents, 47.6% are decided to vaccinate their children against COVID-19. The most common reasons for refusal were inadequate safety information (69%) and worry about side effects (60.6%). Parents have a significantly greater positive attitudes toward children's routine vaccines vs. the COVID-19 vaccine, with higher mean VHS (±SD) = 2.98 ± 0.58 vs. 2.63 ± 0.73, respectively (
p
-value < 0.001). Parents agreed more that routine childhood vaccines are more essential and effective as compared to the COVID-19 vaccine (Cohen's D: 0.946, and 0.826, consecutively;
T
-test
p
-value < 0.00). There is more parental anxiety about serious side effects of the COVID-19 vaccine vs. routine childhood vaccines (Cohen's
D
= 0.706,
p
-value < 0.001). Parents who relied on the Ministry of Health information were more predicted (OR = 1.28,
p
-value = 0.035) to intend to vaccinate as opposed to those who used the WHO website (OR = 0.47, −53%,
p
-value < 0.001). In a multivariate logistic regression analysis, the factors associated with intention to vaccinate children were parents who received COVID-19 vaccine, older parents, having children aged 12–18, and parents with lower education levels.
Conclusions:
Significant proportion of parents are hesitant about the COVID-19 vaccine because they are less confident in its effectiveness, safety, and whether it is essential for their children. Relying on the national official healthcare authority's website for the source of information was associated with increased acceptance of childhood COVID-19 vaccination. As parental intention to vaccinate children against COVID-19 is suboptimal, healthcare authorities could boost vaccine uptake by campaigns targeting hesitant parents.
High quality evidence-based clinical practice guidelines (CPGs) have a major impact on the appropriate diagnosis and management and positive outcomes. The evidence-based healthcare for patients with ...attention deficit hyperactive disorder (ADHD) is challenging. The objective of this study was to appraise the quality of published CPGs for ADHD.
A systematic review was conducted for ADHD CPGs using CPG databases, DynaMed, PubMed, and Google Scholar. The quality of each included CPG was appraised by three independent appraisers using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument.
Six CPGs were critically reviewed. The AGREE II standardized domain scores revealed variation between the quality of these CPGs with the National Institute of Health and Care Excellence (NICE), University of Michigan Health System, and American Academy of Pediatrics CPGs as the top three. Overall, the recommendations for management of ADHD were similar in these CPGs.
Reporting of CPG development is often poorly documented. Guideline development groups should aim to follow the AGREE II criteria to improve the standards and quality of CPGs. The NICE CPG showed the best quality. Embedding the AGREE II appraisal of CPGs in the training and education of healthcare providers is recommended. The protocol for this study was published in PROSPERO (International prospective register of systematic reviews). Link: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017078712 and is additionally available from protocols.io. Link: https://dx.doi.org/10.17504/protocols.io.q27dyhn.
Abstract
Background
Medical training programs candidate’s interview is an integral part of the residency matching process. During the coronavirus disease 2019 (COVID-19) pandemic, conducting these ...interviews was challenging due to infection prevention restrains (social distancing, namely) and travel restrictions. E-interviews were implemented by the Saudi Commission for Healthcare Specialties (SCFHS) since the matching cycle of March 2020 to hold the interviews in a safer virtual environment while maintaining the same matching quality and standards.
Aim
This study was conducted to assess the medical training residency program applicants’ satisfaction, stress, and other perspectives for the (SCFHS) March 2020 Matching-cycle conducted through an urgently implemented E-interviews process.
Method
A cross-sectional, nationwide survey (Additional file 1) was sent to 4153 residency-nominated applicants to the (SCFHS) March 2020 cycle.
Results
Among the 510 candidates who responded, 62.2% applied for medical specialties, 20.2% applied for surgical specialties, and 17.6% applied for critical care and emergency specialties. Most respondents (61.2%) never had previous experience with web-based video conferences. Most respondents (80.2%) used the Zoom application to conduct the current E-interviews, whereas only 15.9% used the FaceTime application. 63.3% of the respondents preferred E-interviews over in-person interviews, and 60.6% rated their experience as very good or excellent. 75.7% of the respondents agreed that all their residency program queries were adequately addressed during the E-interviews. At the same time, 52.2% of them agreed that E-interviews allowed them to represent themselves accurately. 28.2% felt no stress at all with their E-interviews experience, while 41.2% felt little stressed and only 8.2% felt highly stressed. The factors that were independently and inversely associated with applicants’ level of stress with E-interviews experience were their ability to represent themselves during the interviews (
p
= 0.001), cost-savings (
p
< 0.001), their overall rating of the E-interviews quality (
p
= 0.007) and the speed of the internet connection (
p
< 0.006).
Conclusion
Videoconferencing was implemented on an urgent basis during the COVID-19 pandemic in the medical residency application process in Saudi Arabia. It was perceived as an adequate and promising tool to replace in-person interviews in the future. Applicants’ satisfaction was mainly driven by good organization, cost-saving, and their ability to present themselves. Future studies to enhance this experience are warranted.
Brown-Vialetto-Van Laere (BVVL) syndrome is an extremely rare autosomal recessive progressive motoneuron disease that is caused by a defect in the riboflavin transporter genes SLC52A2 and SLC52A3. ...BVVL syndrome has a variable age of presentation, and it is characterized by progressive auditory neuropathy, bulbar palsy, stridor, muscle weakness, and respiratory compromise secondary to diaphragmatic and vocal cord paralysis. BVVL syndrome has a poor prognosis in the absence of treatment, including morbidity with quadriparesis and sensorineural hearing loss, with mortality in the younger age group. Early administration of riboflavin is associated with prolonged survival, low morbidity, and reversal of some clinical manifestations.
We describe an 18-month-old male infant with progressive pontobulbar palsy, loss of developmental milestones, and a clinical picture suggestive of chronic inflammatory demyelinating neuropathy. A nerve conduction study revealed axonal neuropathy, while molecular analysis revealed a homozygous mutation in one of the riboflavin transporter genes, SLC52A3, confirming BVVL syndrome. The patient needed long-term respiratory support and a gastrostomy tube to support feeding. With high-dose riboflavin supplementation, he experienced moderate recovery of motor function.
This report highlights the importance of considering BVVL syndrome in any patient who presents with the clinical phenotype of pontobulbar palsy and peripheral axonal neuropathy, as early riboflavin treatment may improve or halt disease progression, thus reducing the associated mortality and morbidity.
Background: Vitamin D has a role in the pathogenesis of many medical disorders, especially those of the central nervous system. It is essential in maintaining the bone health of children. However, ...patients with epilepsy are at high risk of developing vitamin D deficiency due to antiseizure medications (ASMs). Therefore, we aimed to assess the prevalence of vitamin D deficiency and related risk factors in children with epilepsy. Methods: This is the baseline report of a pragmatic, randomized, controlled, open-label trial that assessed the impact of vitamin D supplementation in preventing vitamin D deficiency (NCT03536845). We included children with epilepsy aged 2–16 years who were treated with ASMs from December 2017 to March 2021. Children with preexisting vitamin D metabolism problems, vitamin-D-dependent rickets, malabsorption syndromes, renal disease, and hepatic disease were excluded. The baseline demographic data, anthropometric measurements, seizure types, epilepsy syndromes, ASMs, and seizure control measures were recorded. Blood tests for vitamin D (25-hydroxyvitamin D 25(OH)D), serum calcium, serum phosphorus, and parathyroid hormone levels were performed. Based on vitamin D concentration, patients were categorized as deficient (<50 nmol/L), insufficient (74.9–50 nmol/L), or normal (>75 nmol/L). Results: Of 159 recruited children, 108 (67.92%) had generalized seizures, 44 (27.67%) had focal seizures, and 7 (4.4%) had unknown onset seizures. The number of children receiving monotherapy was 128 (79.0%) and 31 (19.1%) children were receiving polytherapy. The mean vitamin D concentration was 60.24 ± 32.36 nmol/L; 72 patients (45.28%) had vitamin D deficiency and 45 (28.3%) had vitamin D insufficiency. No significant difference in vitamin D concentration was observed between children receiving monotherapy and those receiving polytherapy. The main risk factors of vitamin D deficiency were obesity and receiving enzyme-inducer ASMs. Conclusions: The prevalence of vitamin D deficiency was high among children with epilepsy. Obese children with epilepsy and those on enzyme-inducer ASMs were at increased risk for vitamin D deficiency. Further studies are needed to establish strategies to prevent vitamin D deficiency.
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.
Galloway-Mowat syndrome is a rare autosomal recessive disease characterized by a unique combination of renal and neurological manifestations, including early-onset steroid-resistant nephrotic ...syndrome, microcephaly, psychomotor delay, and gyral abnormalities of the brain. Most patients die during early childhood. Here, we identified a novel homozygous O-sialoglycoprotein endopeptidase (OSGEP) variant, NM_017807.3:c.973C>G (p.Arg325Gly), in four affected individuals in an extended consanguineous family from Saudi Arabia. We have described the detailed clinical characterization, brain imaging results, and muscle biopsy findings. The described phenotype varied from embryonic lethality to early pregnancy loss or death at the age of 9. Renal disease is often the cause of death. Protein modeling of this OSGEP variant confirmed its pathogenicity. In addition, proteomic analysis of the affected patients proposed a link between the KEOPS complex function and human pathology and suggested potential pathogenic mechanisms.
The COVID-19 pandemic revealed a multidimensional impact on mental health due to health concerns, social distancing and lockdowns, job loss, and limits in institutional support. Accordingly, COVID-19 ...may disproportionally impact families with special educational needs and disabilities (SEND) due to the already high prevalence of mental health conditions in children with SEND and their parents. Hence, it is essential to determine the short-term impact of the pandemic on the mental health of families with SEND to identify their ongoing health, including psychological wellbeing and support needs. The current study examines the anxiety level and concerns of children with SEND and their parents living in Saudi Arabia.
A cross-sectional national study design was utilized as a part of an international consortium using an online Arabic survey. Data were collected from the Ministry of Human Resources and Social Development beneficiaries from May to July 2020. The sample consisted of 1,848 parents of children with SEND aged between 1 and 18 years (mean = 9.66; SD = 4.31). A descriptive and bivariant analysis is reported.
Parental worries on all those concerns when the pandemic started were significantly higher than before the pandemic,
< 0.050. Parental-perceived general anxiety had risen significantly across time,
< 0.001, and their perceived anxiety when the pandemic started exceeded their anxiety before the pandemic,
< 0.001. The general anxiety of children with SEND had risen significantly across time (from before the pandemic to when it had started to during the pandemic),
< 0.001. The children's general worries at the start of the pandemic had correlated significantly and positively with their anxiety, adaptive, maladaptive, and coping efficacies, and parental anxiety scores,
< 0.010 each.
Anxiety levels were high in SEND and their caregivers before and during COVID-19. At the start of the pandemic, the anxiety, adaptive, maladaptive, coping efficacies, and parental anxiety scores of children with SEND were significantly and favorably correlated. These findings support the notion of SEND-specific anxiety and patterns of coping in SEND and their caregivers. The notion also attests to the institutional support required for this specifically vulnerable population during epidemics.
The educational process in different medical schools has been negatively affected by the COVID-19 pandemic worldwide. As a part of the Saudi government's attempts to contain the spread of the virus, ...schools' and universities' educational activities and face-to-face lectures have been modified to virtual classrooms. The purpose of this study was to explore the perceptions of the faculty and the students of an electronic objective structured clinical examination (E-OSCE) activity that took place during the COVID-19 pandemic in the oldest medical school in Saudi Arabia.
An e-OSCE style examination was designed for the final-year medical students by the pediatrics department, College of Medicine at King Saud University in Riyadh, Saudi Arabia. The examination was administered by Zoom™ video conferencing where both students and faculty participated through their laptop or desktop computers. In order to explore the students' and the faculty's perceptions about this experience, a newly designed 13-item online questionnaire was administered at the end of the e-OSCE.
Out of 136 participants (23 faculty and 112 students), 73 respondents (e.g., 54% response rate) filled out the questionnaire. Most of the respondents (69.8%) were very comfortable with this new virtual experience. Most participants (53.4%) preferred the e-OSCE compared to the classic face-to-face clinical OSCE during the pandemic. Regarding the e-OSCE assessment student tool, 46.6% reported that it is similar to the classic face-to-face OSCE; however, 38.4% felt it was worse.
The e-OSCE can be a very effective alternative to the classic face-to-face OSCE due to the current circumstances that still pose a significant risk of infection transmission. Future studies should examine different virtual strategies to ensure effective OSCE delivery from the perspective of both faculty and students.
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