Case report: Clinical and genetic characterization of a novel variant causing pyridoxine-dependent epilepsy, developmental delay, and intellectual disability in two siblings.

Background: Pathogenic variants in are associated with pyridoxine-dependent epilepsy (PDE), a rare autosomal recessive disorder characterized by epileptic seizures, unresponsiveness to standard antiseizure medications (ASM), and a response only to pyridoxine. Here, we report two patients (from a consanguineous family) with neonatal seizures and developmental delay.

Case Presentation: Patient 1 (a 13-year-old girl) was born normally at term.

A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability of ATP8A2-related disorders caused by missense changes.

ATPase, class 1, type 8 A, member 2 (ATP8A2) is a P4-ATPase with a critical role in phospholipid translocation across the plasma membrane. Pathogenic variants in ATP8A2 are known to cause cerebellar ataxia, impaired intellectual development, and disequilibrium syndrome 4 (CAMRQ4) which is often associated with encephalopathy, global developmental delay, and severe motor deficits. Here, we present a family with two siblings born from a consanguineous, first-cousin union from Sudan presenting with global developmental delay, intellectual disability, spasticity, ataxia, nystagmus, and thin corpus callosum.

A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability of -related disorders caused by missense changes.

ATPase, class 1, type 8A, member 2 (ATP8A2) is a P4-ATPase with a critical role in phospholipid translocation across the plasma membrane. Pathogenic variants in are known to cause cerebellar ataxia, mental retardation, and disequilibrium syndrome 4 (CAMRQ4) which is often associated with encephalopathy, global developmental delay, and severe motor deficits. Here, we present a family with two siblings presenting with global developmental delay, intellectual disability, spasticity, ataxia, nystagmus, and thin corpus callosum.

A novel homozygous mutation in TRAPPC9 gene causing autosomal recessive non-syndromic intellectual disability.

Background: The etiology of intellectual disabilities is diverse and includes both genetic and environmental factors. The genetic causes of intellectual disabilities range from chromosomal aberrations to single gene disorders. The TRAPPC9 gene has been reported to cause autosomal recessive forms of intellectual disabilities in 56 patients from consanguineous and non-consanguineous families around the world.

Methylation of alpha-synuclein in a Sudanese cohort.

Background: Several studies suggested a significant role of epigenetic changes, including alterations in miRNA, histone modifications, and DNA methylation of α-synuclein (SNCA) in Parkinson's disease (PD) pathogenicity. As of yet, only very few studies have been carried out in this field in Africa and none in Sudan.

Materials And Methods: We collected DNA from 172 Sudanese individuals (90 cases, 82 controls) who donated saliva for DNA extraction (mean age of onset: 40.

Case Report: A New Family With Pontocerebellar Hypoplasia 10 From Sudan.

Pontocerebellar hypoplasia type 10 (PCH10) is a very rare autosomal recessive neurodegenerative disease characterized by intellectual disability, microcephaly, severe developmental delay, pyramidal signs, mild cerebellar atrophy, and white matter changes in the brain, as shown by magnetic resonance imaging (MRI). The disease has been described in only twenty-one patients from ten Turkish families with a founder missense pathogenic variant in the gene involved in tRNA processing and maturation. We analyzed three siblings from a consanguineous Sudanese family who presented with intellectual disability, dysmorphic features, developmental delay, regression of milestones, microcephaly, epilepsy, extrapyramidal signs, mild pontine, and cerebellar atrophy.

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.

Novel variants causing megalencephalic leukodystrophy in Sudanese families.

Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare form of leukodystrophy characterized by macrocephaly, epilepsy, spasticity, and slow mental deterioration. Genetic studies of MLC are lacking from many parts of the world, especially in Sub-Saharan Africa. Genomic DNA was extracted for 67 leukodystrophic patients from 43 Sudanese families.

Pathogenic Variants in Cause a Novel Psychomotor Developmental Disorder With Spastic Paraplegia.

Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common feature. Abnormalities in multiple cellular processes are implicated in their pathogenesis, including lipid metabolism; but still 40% of the patients are undiagnosed. Our goal was to identify the disease-causing variants in Sudanese families excluded for known genetic causes and describe a novel clinico-genetic entity.

An identical-by-descent novel splice-donor variant in PRUNE1 causes a neurodevelopmental syndrome with prominent dystonia in two consanguineous Sudanese families.

PRUNE1 is linked to a wide range of neurodevelopmental and neurodegenerative phenotypes. Multiple pathogenic missense and stop-gain PRUNE1 variants were identified in its DHH and DHHA2 phosphodiesterase domains. Conversely, a single splice alteration was previously reported.

A children's epilepsy diagnosis aid: Development and early validation using a Bayesian approach.

Introduction: The diagnosis of epilepsy in children is difficult and misdiagnosis rates can be as much as 36%. Diagnosis in all countries is essentially clinical, based on asking a series of questions and interpreting the answers. Doctors experienced enough to do this are either scarce or absent in very many parts of the world so there is a need to develop a diagnostic aid to help less-experienced doctors or non-physician health workers (NPHWs) do this.

Novel Homozygous Missense Mutation in the Gene in a Large Sudanese Family.

Arginases catalyze the last step in the urea cycle. Hyperargininemia, a rare autosomal-recessive disorder of the urea cycle, presents after the first year of age with regression of milestones and evolves gradually into progressive spastic quadriplegia and cognitive dysfunction. Genetic studies reported various mutations in the gene that resulted in hyperargininemia due to a complete or partial loss of arginase activity.

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.

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.

Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556.

Genetic mutations associated with brain malformations can lead to a spectrum of severity and it is often difficult to determine whether there are additional pathogenic variants contributing to the phenotype. Here, we present a family affected by a severe brain malformation including bilateral polymicrogyria, hydrocephalus, patchy white matter signal changes, and cerebellar and pontine hypoplasia with elongated cerebellar peduncles leading to the molar tooth sign. While the malformation is reminiscent of bilateral frontoparietal polymicrogyria (BFPP), the phenotype is more severe than previously reported and also includes features of Joubert syndrome (JBTS).

Impact of PYROXD1 deficiency on cellular respiration and correlations with genetic analyses of limb-girdle muscular dystrophy in Saudi Arabia and Sudan.

Next-generation sequencing is commonly used to screen for pathogenic mutations in families with Mendelian disorders, but due to the pace of discoveries, gaps have widened for some diseases between genetic and pathophysiological knowledge. We recruited and analyzed 16 families with limb-girdle muscular dystrophy (LGMD) of Arab descent from Saudi Arabia and Sudan who did not have confirmed genetic diagnoses. The analysis included both traditional and next-generation sequencing approaches.

The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy - A randomized, double-blind, placebo-controlled trial.

Objectives: The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with drug-resistant epilepsy (DRE) was investigated.

Congenital brain malformations in Sudanese children: an outpatient-based study.

Congenital brain malformations (CBMs) are a heterogeneous group characterised by abnormal structure of the developing brain. Their aetiology includes in-utero infections, teratogenicity and in a considerable group, genetic causes. Due to the high rate of consanguineous marriages and the possible high prevalence of prenatal infections in Sudan, CBMs are likely to be common.

Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family.

Background: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent.

Clinical Profile of Pediatric Neurological Disorders: Outpatient Department, Khartoum, Sudan.

Background: There is no available data from Sudan reflecting the magnitude of the neurological disorders and disabilities in the pediatric age-group. This study aims to evaluate the pattern of neurological disorders among Sudanese children.

Patients And Methods: This is a retrospective survey of children with epilepsy and other neurodisability disorders seen at pediatric neurology outpatient clinic, during the period from January 2007 to August 2013.

Brain tuberculoma, an unusual cause of stroke in a child with trisomy 21: a case report.

Background: Tuberculosis remains a public health problem in developing countries and is associated with lethal central nervous system complications. Intracranial tuberculomas occur in 13% of children with neurotuberculosis. Patients with trisomy 21 have an increased risk for stroke, which usually stems from cardiovascular defects.