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.

Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome.

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.

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.