Genetic diagnosis in Sudanese and Tunisian families with syndromic intellectual disability through exome sequencing.

BACKGROUND: Intellectual disability is a form of neurodevelopmental disorders that begin in childhood and is characterized by substantial intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Several genetic and nongenetic factors contribute to its development; however, its most severe forms are generally attributed to single-gene defects. High-throughput technologies and data sharing contributed to the diagnosis of hundreds of single-gene intellectual disability subtypes. METHOD: We applied exome sequencing to identify potential variants causing syndromic intellectual disability in six Sudanese patients from four unrelated families. Data sharing through the Varsome portal corroborated the diagnosis of one of these patients and a Tunisian patient investigated through exome sequencing. Sanger sequencing validated the identified variants and their segregation with the phenotypes in the five studied families. RESULT: We identified three pathogenic/likely pathogenic variants in CCDC82, ADAT3, and HUWE1 and variants of uncertain significance in HERC2 and ATP2B3. The patients with the CCDC82 variants had microcephaly and spasticity, two signs absent in the two previously reported families with CCDC82-related intellectual disability. CONCLUSION: In conclusion, we report new patients with pathogenic mutations in the genes CCDC82, ADAT3, and HUWE1. We also highlight the possibility of extending the CCDC82-linked phenotype to include spastic paraplegia and microcephaly.

Intelligence quotient (IQ) among children with epilepsy: National epidemiological study - Sudan.

BACKGROUND: Many studies of selected groups of children with epilepsy have demonstrated an association between epilepsy and cognitive deficits. The aim of this study was to assess the intellectual skills of children with epilepsy and to investigate the influence of gender, age at seizure onset, type of epilepsy, antiepileptic drug used, and control of epilepsy on their intellectual function. METHODS: This is a descriptive prospective study in which one hundred and eighty-seven patients at school age (6-14 years) were recruited. Epilepsy was classified using the International League Against Epilepsy (ILAE) Commission on Classification and Terminology 2005-2009 report. An intelligence quotient (IQ) test was conducted to all patients using Stanford-Binet Fifth Edition (SB5)/Arabic version. RESULTS: Eighty-eight (47.1%) patients had an average score on Full Scale IQ (FSIQ), 44 (23.5%) had low average, whereas 18 (9.6%) had borderline impaired or delayed score. In the nonverbal IQ (NVIQ) score, the majority 84 (44.9%) had average score. The performance of the patients in the nonverbal score is better than in the verbal score, which was found to be statistically significant (P-value = 0.01). The FSIQ score was negatively affected by younger age at onset of epilepsy, polytherapy, and uncontrolled seizures. CONCLUSIONS: Most of children with epilepsy had an average FSIQ; uncontrolled seizure had worse effect on overall FSIQ and memory. Interventions to support children with epilepsy should focus on epilepsy management and school psychosocial domains.

Classification and management of epilepsy and epileptic syndromes in a cohort of 202 school children- a 2 year follow up study- Sudan.

BACKGROUND: In this paper, seizure types, and epilepsy syndromes are elucidated as per ILAE (2010) classification. A brief outline of the antiepileptic drug regimens used and the outcome of seizure control in a two -year period is presented. The applicability of the ILAE classification in resource limited countries has been revisited. METHODS: This is a descriptive prospective study, in which 202 patients were enrolled. The Cohort group was seen and evaluated by a pediatric neurologist at the Pediatric neurology Outpatients Department (OPD). Epilepsy was classified using the International League Against Epilepsy (ILAE) classification (2005-2009) report. All patients had an Electroencephalogram (EEG) at the start of the study, and this was repeated as deemed appropriate. Brain imaging (MRI) was done to patients when indicated. Treatment decisions were made by pediatric neurologists. Outcomes were categorized into four groups: fully recovered, well controlled, partially controlled and uncontrolled. RESULTS: The mean age is 10.5 + 2.7 years. Male to female ratio was 1.7: 1. Thirty five (17.3%) patients had generalized onset seizures, 46(22.8%) had focal onset seizures, 104(51.5%) had a specific epilepsy syndrome, and 17(8.4%) patients were unclassified. 170 (84.2%) patients were on mono-therapy on their initial visit, 30(14.8%) were on two Antiepileptic Drugs (AEDs) while two (1.0%) patients were on poly-therapy. After 2 years; 155(76.7%) patients were on mono-therapy, 36(17.8%) on two AEDs while ten were (4.0%) on polytherapy. One eighty (88.2%) patients were controlled. Fifteen (7.4%) of them were off medication after being seizure free for 2 years. Twenty (9.8%) have partial control, while two (1.0%) patients were uncontrolled. Patients with focal epilepsy, those on polytherapy and those with abnormal imaging had poor prognosis. CONCLUSIONS: The ILAE classification can be used in resource limited countries. Childhood epilepsies have a good prognosis provided they are well classified and treated.