Comparative genetic diagnostic evaluation of pediatric neuromuscular diseases in a consanguineous population.

Neuromuscular diseases (NMD) are a group of neurological diseases that manifest with various clinical symptoms affecting different components of the peripheral nervous system, which play a role in voluntary body movements control. The primary objective of this study is to explore the diagnostic efficacy of a combined genetic and biochemical testing approach for patients with neuromuscular diseases with diverse presentations in a population with high rate of consanguinity. Genetic testing was performed using selected Next Generation Sequencing (NGS) gene panels and whole exome sequencing on the peripheral blood sample from the patients.

On Seizures and Knives: Perampanel-Induced Psychosis: A Case Report and Literature Review.

Managing epilepsy in the context of intellectual disability can be complicated as this population is known to have higher rates of drug resistance and sensitivity to side effects of antiseizure medications (ASMs). Perampanel is a novel ASM recently approved as an adjunctive treatment for drug resistant focal seizures. It carries a black-box warning for serious psychiatric and behavioral adverse reactions of aggression, irritability, et cetera.

Diagnostic evaluation of patients with epileptic spasms in the era of next-generation sequencing.

Objective: Epileptic spasms (ES) can be caused by a variety of etiologies. However, in almost half of cases, the etiology is unidentified. With the advent of next-generation sequencing (NGS), the recognition of genetic etiologies has increased.

STAC3-related myopathy: A Report of a Cohort of Seven Saudi Arabian Patients.

Aim: The study aims to review all the genetically confirmed STAC3-related myopathy being followed in a single center in the Eastern Province of Saudi Arabia.

Methodology: A retrospective review of all genetically confirmed STAC3-related myopathy followed in our clinic has been conducted.

Results: 7 patients with STAC3-related myopathy have been found in our cohort, with all the patients presenting with infantile hypotonia, myopathic facies, and muscle weakness in the first year of life.

The socioeconomic burden of spinal muscular atrophy in Saudi Arabia: a cross-sectional pilot study.

Background: Spinal muscular atrophy (SMA) is a rare debilitating condition with a significant burden for patients and society. However, little is known about how it affects Saudi Arabia's population. The socioeconomic and medical characteristics of affected SMA patients and their caregivers are lacking.

Identifying Clinical and Genetic Characteristics of Spinal Muscular Atrophy Patients and Families in Saudi Arabia.

Introduction:  Spinal muscular atrophy (SMA) is an inherited, neuromuscular disease characterized by the deterioration of spinal motor neurons, causing progressive muscular atrophy and weakening. It is an autosomal recessive disease with the mutation of the survival motor neuron 1 (SMN1) gene as a hallmark. Evidence suggests that the SMN2 gene modulates the severity of the disease.

Clinical phenotype associated with variants in TANGO2: A case study.

Transport and Golgi organization 2 (TANGO2) disease is a severe inherited disorder that presents with multiple symptoms and a broad spectrum of phenotypes, including metabolic crisis, encephalopathy, cardiac arrhythmia, and hypothyroidism. The clinical picture of a TANGO2 gene biallelic mutation involves encephalopathy and rhabdomyolysis and is marked by cardiac rhythm disorders and neurological regression. The presentation of encephalopathy varies and can range from isolated language delay and cognitive impairment to multiple disabilities and spastic quadriparesis.

SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population.

The uptake and efflux of solutes across a plasma membrane is controlled by transporters. There are two main superfamilies of transporters, adenosine 5'-triphosphate (ATP) binding cassettes (ABCs) and solute carriers (SLCs). In the brain, SLC transporters are involved in transporting various solutes across the blood-brain barrier, blood-cerebrospinal fluid barrier, astrocytes, neurons, and other brain cell types including oligodendrocytes and microglial cells.

Case Report: The Genetic Diagnosis of Duchenne Muscular Dystrophy in the Middle East.

The timely and accurate genetic diagnosis of Duchenne muscular dystrophy (DMD) enables prompt initiation of disease management and genetic counseling and optimal patient care. Despite the existence of best practice guidelines for the diagnosis of DMD, implementation of these recommendations in different parts of the world is challenging. Here, we present 4 unique case studies which illustrate the different diagnostic pathways of patients with DMD in Middle Eastern countries and highlight region-specific challenges to achieving timely and accurate genetic diagnosis of DMD.

Incidental Finding of MEGDEL Syndrome Based on Neuroimaging: Case Report.

MEGDEL 3-methylglutaconic (MG) aciduria, deafness, encephalopathy, Leigh-like syndrome is an autosomal recessive disorder associated with infantile hypoglycemia, progressive psychomotor developmental delay, cerebellar atrophy with lesions in the basal ganglia, spasticity, dystonia, deafness, and transient liver problems, which typically occur in the first year of life. Other clinical presentations include failure to thrive, epilepsy, and optic nerve atrophy. The serine active site-containing 1 (SERAC1) mutation is localized at the mitochondria-associated membranes, which are responsible for encoding a phosphatidylglycerol remodeler essential for both mitochondrial function and intracellular cholesterol trafficking and is thus responsible for the disease.

Successful treatment of epilepsia partialis continua with perampanel: two pediatric cases.

Epilepsia partialis continua (EPC) is a form of focal motor status epilepticus, associated with multiple etiologies. Etiology-specific treatments, such as hemispherotomy for Rasmussen encephalitis, lesionectomy for focal cortical dysplasia, and metabolic correction for non-ketotic hyperglycemia, have proven to be efficacious in treating EPC, but, in general, EPC is difficult to treat and often drug-resistant, and there is little evidence to guide therapy. We report the successful treatment of EPC with perampanel in two pediatric patients.

Consensus Statement on the Management of Duchenne Muscular Dystrophy in Saudi Arabia During the Coronavirus Disease 2019 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has caused overwhelming challenges in healthcare worldwide. During such an outbreak, some needs of high-risk groups who require regular follow-ups and long-term management are not met. The vulnerable populations include patients with Duchenne muscular dystrophy (DMD).

Selenoprotein N-related myopathy: a retrospective natural history study to guide clinical trials.

Objective: To describe clinical features and disease progression of Selenoprotein N-related myopathy in a large multicenter cohort of patients.

Methods: Cross-sectional multicenter data analysis of 60 patients (53 families) with Selenoprotein N-related myopathy and single-center retrospective longitudinal analysis of 25 patients (21 families) over a median period of 5.3 years.

Gender and Hemispheric Differences in Epilepsy Diagnosed by Voxel-based Morphometry (VBM) Method: a Pilot Cortical Thickness Study.

Introduction: Voxel-based morphometry (VBM) is a neuroimaging analysis technique that allows investigation of focal differences in brain anatomy, using the statistical approach of statistical parametric mapping. Gender changes are probably expressed in the human brain in the form of functional and anatomical organization.

Aim: Our aim was to study gender differences and anatomical abnormalities in epilepsy patients (EP) by voxel-based morphometry (VBM) methods.

-associated congenital fiber-type disproportion and cardiomyopathy with variants in additional neuromuscular disease genes; the dilemma of panel testing.

Next-generation sequencing has led to transformative advances in our ability to diagnose rare diseases by simultaneously sequencing dozens, hundreds, or even entire genomes worth of genes to efficiently identify pathogenic mutations. These studies amount to multiple hypothesis testing on a massive scale and not infrequently lead to discovery of multiple genetic variants whose relative contributions to a patient's disease are unclear. Panel testing, in particular, can be problematic because each of the many genes being sequenced might represent a plausible explanation for a given case.

Spectrum of Neuromuscular Disorders With HyperCKemia From a Tertiary Care Pediatric Neuromuscular Center.

Elevated creatine kinase is a useful screening test in the diagnostic workup of patients with neuromuscular disorders. We did a retrospective study of children with hyperCKemia (>175 IU/L) who were followed in the neuromuscular program of a tertiary care pediatric center from 2005 to 2016. Patients with hyperCKemia were divided into 2 groups: myopathic and nonmyopathic.

Neuralgic amyotrophy in children.

Introduction: Neuralgic amyotrophy (NA) is characterized by the clinical triad of pain, muscle weakness/atrophy, and sensory symptoms.

Methods: We retrospectively identified children (≤18 years old) over the course of 15 years (2003-2017) at a single pediatric center.

Results: We included 22 patients (8 females and 14 males, 6-18 years old); pain was the presenting manifestation in all of them.

Brain involvement in Charcot-Marie-Tooth disease due to ganglioside-induced differentiation associated-protein 1 mutation.

Charcot-Marie-Tooth (CMT) due to ganglioside-induced differentiation associated-protein 1 (GDAP1) gene mutation can be inherited as an autosomal recessive (severe phenotype) or dominant (milder phenotype) disorder. GDAP1 protein, located in the outer mitochondrial membrane, is involved in the mitochondrial fission. Brain imaging abnormalities have not been reported in this condition.

Spectrum of Nondystrophic Skeletal Muscle Channelopathies in Children.

Background: The nondystrophic skeletal muscle channelopathies are a group of disorders caused by mutations of various voltage-gated ion channel genes, including nondystrophic myotonia and periodic paralysis.

Methods: We identified patients with a diagnosis of muscle channelopathy from our neuromuscular database in a tertiary care pediatric center from 2005 to 2015. We then performed a retrospective review of their medical records for demographic characteristics, clinical features, investigations, treatment, and follow-up.