Family-base rare variant association analysis in Saudi Arabian hydrocephalus subjects using whole exome sequencing.

BACKGROUND: Hydrocephalus is a highly heterogeneous multifactorial disease that arises from genetic and environmental factors. Familial genetic studies of hydrocephalus have elucidated four robustly associated hydrocephalus associated loci. This study aims to identify potential genetic causation in cases of hydrocephalus, with or without spina bifida and Dandy Walker Syndrome (DWS), using family-based rare variant association analysis of whole exome sequencing. METHODS: We performed whole exome sequencing in 143 individuals across 48 families where at least one offspring was affected with hydrocephalus (N.=27), with hydrocephalus with spina bifida (N.=21) and with DWS (N.=3), using Illumina HiSeq 2500 instrument. RESULTS: No pathogenic or putative pathogenic single-nucleotide variants were evident in the four known hydrocephalus loci in our subjects. However, after examining 73 known hydrocephalus genes previously identified from literature, we identified three potentially impactful variants from the cohort. Using a gene panel comprising variants in known neural tube defects loci, we identified a total of 1024 potentially deleterious variants, of which 797 were missense variants and 191 were frameshift variants, 36 were stop gain/loss variants. A small portion of our family pedigree analyses yielded putative genetic signals which may be responsible for hydrocephaly elated phenotypes, however the low diagnostic yield may be due to lack of capture of genetic variants in the exonic regions i.e. structural variants may only be evident from whole genome sequencing. CONCLUSIONS: We identified three potentially impactful variants from our cohort in 73 known hydrocephalus genes previously identified in literature.

Whole-exome sequencing of a Saudi epilepsy cohort reveals association signals in known and potentially novel loci.

BACKGROUND: Epilepsy, a serious chronic neurological condition effecting up to 100 million people globally, has clear genetic underpinnings including common and rare variants. In Saudi Arabia, the prevalence of epilepsy is high and caused mainly by perinatal and genetic factors. No whole-exome sequencing (WES) studies have been performed to date in Saudi Arabian epilepsy cohorts. This offers a unique opportunity for the discovery of rare genetic variants impacting this disease as there is a high rate of consanguinity among large tribal pedigrees. RESULTS: We performed WES on 144 individuals diagnosed with epilepsy, to interrogate known epilepsy-related genes for known and functional novel variants. We also used an American College of Medical Genetics (ACMG) guideline-based variant prioritization approach in an attempt to discover putative causative variants. We identified 32 potentially causative pathogenic variants across 30 different genes in 44/144 (30%) of these Saudi epilepsy individuals. We also identified 232 variants of unknown significance (VUS) across 101 different genes in 133/144 (92%) subjects. Strong enrichment of variants of likely pathogenicity was observed in previously described epilepsy-associated loci, and a number of putative pathogenic variants in novel loci are also observed. CONCLUSION: Several putative pathogenic variants in known epilepsy-related loci were identified for the first time in our population, in addition to several potential new loci which may be prioritized for further investigation.

Comparison between esomeprazole 20 mg Vs 40 mg as stress ulcer prophylaxis (SUP) in critically ill patients: A retrospective cohort study.

Critically ill patients admitted to intensive care units (ICUs) are at high risk of developing upper gastrointestinal bleeding due to GI stress ulceration (SU). The major independent risk factors for the development of GI bleeding in the ICUs include mechanical ventilation (MV) and coagulopathy. There is no enough evidence regarding the most appropriate dosing of esomeprazole as stress ulcer prophylaxis (SUP) in critically ill patients. This is a retrospective cohort study conducted at King Abdulaziz Medical City-Riyadh between January and December 2018 to determine the efficacy and safety of two different regimens of esomeprazole (20 vs 40 mg) as SUP in critically ill patients with major risk factors of GI stress ulceration. A total of 1864 patients were reviewed, 387 patients meeting inclusion criteria were enrolled. The propensity score was used to adjust for clinically and statistically relevant variables. We considered a P value of <.05 as statistically significant. 49 patients (12.6%) had received Esomeprazole 20 mg during the study period. Compared with Esomeprazole 20 mg, Esomeprazole 40 mg was not superior in GI bleeding prevention (aOR 2.611, 95% CI 0.343-20.247, P = .356). In addition, neither ICU C. difficle, ICU mortality within 30 days, ICU LOS, hospital LOS, ICU re-admission within 6 months, RBCs transfusion, nor platelets transfusion requirements were significant. On the other hand, Esomeprazole 40 mg was statistically associated with Enterobacteriaceae, Pneumonia, and longer MV duration.

A Case of Trigeminal Schwannoma Presenting as a Parasellar Mass.

Schwannoma's of considerable size arising from the trigeminal nerve are very rare. Here, a case of a large right-sided parasellar mass diagnosed as a trigeminal schwannoma is reported. Complete resection of the tumor was successfully achieved. The patient had an excellent postoperative course.

Adult Desmoplastic Medulloblastoma.

Medulloblastoma is more common in young age and rare in adult age. Some characteristics that characterize medulloblastoma in adults compared with children: Lateral cerebellar location, heterogeneous signal intensity on magnetic resonance imaging, desmoplastic histological variant and more favorable prognosis. Preoperative diagnosis is important for correct management of these patients. However, because of the low incidence of medulloblastoma in adults, preoperative diagnosis still challenging and prognostic factors and best treatment options are still controversial. We report a case of a 31-year-old male patient who presented with a rare case of posterior fossa medulloblastoma.

Mixed vestibular schwannoma and meningioma without neurofibromatosis.

The co-existence of meningioma and schwannoma as 2 distinct histologic components within the same tumor has been described in neurofibromatosis 2 (NF2), but the co-existence of both tumors without evidence of NF2 is much rarer. Here, we are reporting a case of mixed schwannoma with meningioma without clinical evidence of NF2. In an adult Saudi lady with progressive left-sided hearing loss, left cerebellopontine tumor was diagnosed by MRI, and the histopathological diagnosis revealed that this tumor was composed of vestibular schwannoma and meningioma. This case is discussed with literature review.

In uteroventriculo-amniotic shunt for hydrocephalus.

INTRODUCTION: Hydrocephalus is one of the most common congenital anomalies affecting the central nervous system especially in developing countries for several reasons including prohibition of abortion in many countries. The technological advances in methods of intrauterine diagnosis of congenital malformation made it possible to detect early enlargement of the ventricles and diagnose hydrocephalus as early as 15 weeks of gestational age. Many trials of intrauterine shunting proved unsuccessful, mainly because of complications such as intra- or extracranial shunt migration, obstruction, infection, and malposition. CASE REPORT: The author is presenting a case of a successful ventriculo-amniotic shunt utilizing Al-Anazi ventriculo-uterine shunt, which is easy to implant. It has a one-way valve to prevent amniotic fluid backflow and special wings to prevent shunt migration, which are both relatively short and wide to reduce the possibility of malfunction and the risk of infection because there is no exposure with the external environment. CONCLUSION: Our successful trial showed that Al-Anazi ventriculo-uterine shunt might be the first step in treating congenital hydrocephalus.

Experience with severe head injury and role of intracranial pressure monitoring in Eastern Saudi Arabia.

OBJECTIVE: Severe head injury is the leading cause of death in the younger age group and it is an epidemic health problem in Saudi Arabia. Several factors contribute to this observation. These include socio-economic prosperity, poor driving behavior and attitudes. The study was conducted to determine the magnitude of severe head injury in the Eastern Province of the Kingdom of Saudi Arabia (KSA) and to emphasize the importance of application of intracranial pressure (ICP) monitoring in severe head injury. METHODS: A retrospective study of 178 patients admitted to King Fahad Hospital of the University, Al-Khobar, KSA during the period from 1992-2002 with severe head injury Glasgow coma score (GCS) <\=8 included the analysis and correlation of clinical and radiological factors such as age, sex, nationality, cause of the trauma, epilepsy, alcohol intake, extracranial injuries, x-ray findings, CT scan findings, surgical intervention, and application of the ICP monitor to the outcome. The data were subjected to detailed analysis using the Statistical Package for Social Sciences version 10. RESULTS: The study group was divided into 2; the first group consisted of patients treated without the application of the ICP monitor and consisted of 126 patients, and the outcome was satisfactory (good recovery or moderate disability) in 38% and 62% had poor outcome (severe disability or death). The second group was 52 patients where ICP monitor was used. Two thirds of them showed high ICP. The outcome in this group was satisfactory in 77% and poor in 23%. CONCLUSION: Severe head injury is a major health hazard leading to a high rate of morbidity, disability and death. The benefit of an ICP monitor should be clearly illustrated to all neurosurgical centers in KSA in order to consider routine and early applications of ICP monitoring as one of the basic measures in severely head injured patients.