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Cureus May 2024Background Cerebral palsy (CP) is a major cause of childhood motor impairment worldwide. The prevalence of CP related to preterm births has increased consistently....
Background Cerebral palsy (CP) is a major cause of childhood motor impairment worldwide. The prevalence of CP related to preterm births has increased consistently. Perinatal hypoxic-ischemic encephalopathy, intra- or periventricular haemorrhage, cerebral dysgenesis and intracranial infections are among the factors contributing to CP onset. Several studies have explored epilepsy-related morbidity among children with CP, finding notable correlations between the two conditions. Worldwide, there are multiple studies highlighting the high prevalence of epilepsy among children with CP and its association with specific CP subtypes and neurologic insults. However, research on the risk factors for epilepsy in CP children is limited, particularly in the Middle East and Saudi Arabia. Aim This study aims to address this gap by analysing potential prenatal, antenatal, and postnatal risk factors associated with epilepsy development in children with CP. Methods A retrospective cohort analysis of 152 children aged 1-14 years diagnosed with CP at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, was conducted. Results The study showed a significant prevalence of epilepsy (68.4%), with generalised seizures being the most common type. Quadriplegia was notably common among CP children with epilepsy, indicating a potential correlation between motor impairment severity and epilepsy risk. Furthermore, CP children with epilepsy exhibited a higher prevalence of co-morbidities, emphasising the multifaceted nature of this condition. Perinatal and neonatal factors, such as hypoxic events, mechanical ventilation, perinatal asphyxia, neonatal convulsions, and microcephaly, were identified as significant risk factors for epilepsy in children with CP. While speech and hearing disorders were present in CP children with and without epilepsy, a slightly higher prevalence of impaired speech was observed in those with epilepsy. However, the difference between the two groups was not significant. Conclusion This study provides valuable insights into the epidemiology, clinical characteristics and potential risk factors associated with epilepsy among children diagnosed with CP in Saudi Arabia. The findings underscore the complexity of managing epilepsy in this population and highlight the need for further research to elucidate the underlying mechanisms and support the development of targeted interventions to improve patient outcomes.
PubMed: 38854260
DOI: 10.7759/cureus.59980 -
Neurobiology of Disease Jun 2024Bioenergetics describe the biochemical processes responsible for energy supply in organisms. When these changes become dysregulated in brain development, multiple... (Review)
Review
Bioenergetics describe the biochemical processes responsible for energy supply in organisms. When these changes become dysregulated in brain development, multiple neurodevelopmental diseases can occur, implicating bioenergetics as key regulators of neural development. Historically, the discovery of disease processes affecting individual stages of brain development has revealed critical roles that bioenergetics play in generating the nervous system. Bioenergetic-dependent neurodevelopmental disorders include neural tube closure defects, microcephaly, intellectual disability, autism spectrum disorders, epilepsy, mTORopathies, and oncogenic processes. Developmental timing and cell-type specificity of these changes determine the long-term effects of bioenergetic disease mechanisms on brain form and function. Here, we discuss key metabolic regulators of neural progenitor specification, neuronal differentiation (neurogenesis), and gliogenesis. In general, transitions between glycolysis and oxidative phosphorylation are regulated in early brain development and in oncogenesis, and reactive oxygen species (ROS) and mitochondrial maturity play key roles later in differentiation. We also discuss how bioenergetics interface with the developmental regulation of other key neural elements, including the cerebrospinal fluid brain environment. While questions remain about the interplay between bioenergetics and brain development, this review integrates the current state of known key intersections between these processes in health and disease.
PubMed: 38849103
DOI: 10.1016/j.nbd.2024.106550 -
Genetic Microcephaly in a Saudi Population: Unique Spectrum of Affected Genes Including a Novel One.Journal of Child Neurology May 2024Genetic microcephaly is linked to an increased risk of developmental disabilities, epilepsy, and motor impairment. The aim of this study is to describe the spectrum of...
Genetic microcephaly is linked to an increased risk of developmental disabilities, epilepsy, and motor impairment. The aim of this study is to describe the spectrum of identifiable genetic etiologies, clinical characteristics, and radiologic features of genetic microcephaly in patients referred to a tertiary center in Saudi Arabia. This is a retrospective chart review study of all patients with identifiable genetic microcephaly presenting to a tertiary center in Saudi Arabia. The patients' demographics, clinical, laboratory, radiologic, and molecular findings were collected. Of the total 128 cases referred, 52 cases (40%) had identifiable genetic causes. Monogenic disorders were found in 48 cases (92%), whereas chromosomal disorders were found in only 4 cases (8%). Developmental disability was observed in 40 cases (84%), whereas only 8 cases (16%) had borderline IQ or mild developmental delay. Epilepsy was seen in 29 cases (56%), and motor impairment was seen in 26 cases (50%). Brain magnetic resonance imaging (MRI) revealed abnormalities in 26 (50%) of the cohort. Hereditary neurometabolic disorders were seen in 7 (15%) of the 48 cases with monogenic disorders. The most common gene defect was , which is responsible for primary microcephaly type 5 and was seen in 10 cases (19%). A novel gene pathogenic mutation was seen in 3 cases (6%). Single gene defect is common in this Saudi population, with the gene being the most common. Hereditary neurometabolic disorders are a common cause of genetic microcephaly. Furthermore, we propose the gene mutation as a possible novel cause of genetic microcephaly.
Topics: Humans; Microcephaly; Saudi Arabia; Male; Female; Retrospective Studies; Child, Preschool; Child; Infant; Adolescent; Nerve Tissue Proteins; Magnetic Resonance Imaging; Developmental Disabilities; Epilepsy; Mutation; Brain
PubMed: 38847106
DOI: 10.1177/08830738241252848 -
Molecular Syndromology Jun 2024The Witteveen-Kolk syndrome (WITKOS) (OMIM: 613406) is a heterogeneous emerging disorder caused by pathogenic variants or microdeletions encompassing the gene (SIN3...
INTRODUCTION
The Witteveen-Kolk syndrome (WITKOS) (OMIM: 613406) is a heterogeneous emerging disorder caused by pathogenic variants or microdeletions encompassing the gene (SIN3 Transcription Regulator Family Member A). It is characterized by distinctive facial features, developmental delay, intellectual disability, microcephaly, short stature, and subtle anomalies on brain magnetic resonance imaging (MRI). To date, about 50 patients have been reported in the medical literature.
PATIENT PRESENTATION
In this article, we reported a patient with classic findings of WITKOS including global developmental delay, microcephaly, hypotonia, vomiting, malnutrition, autistic and dysmorphic facial features, and cardiac abnormalities. Also, a barium esophagogram suggested severe motility disorder and gastroesophageal reflux disease. Affymetrix CytoScan 750K microarray showed a de novo 1.6-Mb deletion at 15q24.1q24.2, including the whole gene. We have also summarized the clinical features of WITKOS patients in the medical literature and cardiac abnormalities detected in 4 out of 10 patients in studies that clearly state that cardiac examination was performed in the patients.
CONCLUSION
Our findings showed that cardiac defects are not uncommon findings in WITKOS. Physicians should also be aware of reflux disease and motility disorder in patients with feeding difficulty together with early cardiac examination in terms of an improved quality of life in WITKOS patients.
PubMed: 38841330
DOI: 10.1159/000536072 -
Molecular Syndromology Jun 2024Vici syndrome is an ultra-rare, congenital disorder of autophagy characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency,...
INTRODUCTION
Vici syndrome is an ultra-rare, congenital disorder of autophagy characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Patients usually present in the neonatal period or infancy with profound hypotonia, based on information available from the nearly 100 cases reported to date.
CASE PRESENTATION
We present 3 new cases of Vici syndrome confirmed by genetic analysis of gene. The 3 male patients had neonatal hypotonia, progressive microcephaly, psychomotor retardation, recurrent respiratory tract infections, optic atrophy, and failure to thrive, but no cataracts or hepatomegaly. Three disease-causing variants in homozygous state were detected in the gene: two novel c.1652C>T and c.7557+2T>C forms; and one previously reported c.7447C>T. The patient, who was homozygous for the c.1652C>T mutation, presented with neonatal onset seizures that had not been reported previously.
DISCUSSION/CONCLUSION
The present study provides data for the evaluation of the natural history and genotype-phenotype correlations for treatment options that are expected to be available in the future.
PubMed: 38841323
DOI: 10.1159/000536069 -
Molecular Syndromology Jun 2024Hydroxysteroid 17-beta dehydrogenase type 10 (HSD10) protein is a mitochondrial enzyme. Multisystemic involvement occurs in HSD10 deficiency as in other mitochondrial...
INTRODUCTION
Hydroxysteroid 17-beta dehydrogenase type 10 (HSD10) protein is a mitochondrial enzyme. Multisystemic involvement occurs in HSD10 deficiency as in other mitochondrial diseases. HSD10 deficiency (disease) is rare. Less than 40 index cases have been reported so far. A female patient is even rarer because of X-linked transmission. Five index female cases have been reported.
CASE PRESENTATION
We report a three-year-old female patient who was investigated due to microcephaly and global developmental delay. She had significant dysmorphic findings. The tiglylglycine peak was detected in urinary organic acid analysis. Other metabolic investigations and laboratory tests were unremarkable. Mild cerebral atrophy, mild ventricular dilation, thin corpus callosum, and an increase in T2 signal in the globus pallidus were revealed at brain magnetic resonance imaging. Heterozygous novel mutation in the gene was found by whole-exome sequencing (WES) analysis. We started isoleucine-restricted diet and a "cocktail" of the mitochondrial vitamin.
DISCUSSION/CONCLUSION
We will see HSD10 disease patients more frequently with the increasing use of WES and genetic panels. Thus, different findings and phenotypes of the HSD10 disease will be revealed.
PubMed: 38841322
DOI: 10.1159/000535589 -
Hormone Research in Paediatrics Jun 2024The diagnostic yield of genetic analysis in the evaluation of children with short stature depends on associated clinical characteristics, but the additional effect of...
INTRODUCTION
The diagnostic yield of genetic analysis in the evaluation of children with short stature depends on associated clinical characteristics, but the additional effect of parental consanguinity has not been well documented.
METHODS
This observational case series of 42 short children from 34 consanguineous families was collected by six referral centres of paediatric endocrinology (inclusion criteria: short stature and parental consanguinity). In 18 patients (12 families, group 1), the clinical features suggested a specific genetic defect in the growth hormone (GH) insulin-like growth factor I (IGF-I) axis, and a candidate gene approach was used. In others (group 2), a hypothesis-free approach was chosen (gene panels, microarray analysis, and whole exome sequencing) and further subdivided into 11 patients with severe short stature (height <-3.5 standard deviation score [SDS]) and microcephaly (head circumference <-3.0 SDS) (group 2a), 10 patients with syndromic short stature (group 2b), and 3 patients with nonspecific isolated GH deficiency (group 2c).
RESULTS
In all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, and STAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4, and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1, and 17p13.3 microdeletions. In group 2c, no genetic cause was found. Homozygous, compound heterozygous, and heterozygous variants were found in 21, 1, and 4 patients, respectively.
CONCLUSION
Genetic testing in short children from consanguineous parents has a high diagnostic yield, especially in cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature.
PubMed: 38838658
DOI: 10.1159/000539696 -
Clinical Genetics Jun 2024Microcephalic osteodysplastic primordial dwarfism type I (MOPDI) is a very rare and severe autosomal recessive disorder characterized by marked intrauterine growth...
Microcephalic osteodysplastic primordial dwarfism type I (MOPDI) is a very rare and severe autosomal recessive disorder characterized by marked intrauterine growth retardation, skeletal dysplasia, microcephaly and brain malformations. MOPDI is caused by biallelic mutations in RNU4ATAC, a non-coding gene involved in U12-type splicing of 1% of the introns in the genome, which are recognized by their specific splicing consensus sequences. Here, we describe a unique observation of immunodeficiency in twin sisters with mild MOPDI, who harbor a novel n.108_126del mutation, encompassing part of the U4atac snRNA 3' stem-loop and Sm protein binding site, and the previously reported n.111G>A mutation. Interestingly, both twin sisters show mild B-cell anomalies, including low naive B-cell counts and increased memory B-cell and plasmablasts counts, suggesting partial and transitory blockage of B-cell maturation and/or excessive activation of naive B-cells. Hence, the localization of a mutation in stem II of U4atac snRNA, as observed in another RNU4ATAC-opathy with immunodeficiency, that is, Roifman syndrome (RFMN), is not required for the occurrence of an immune deficiency. Finally, we emphasize the importance of considering immunodeficiency in MOPDI management to reduce the risk of serious infectious episodes.
PubMed: 38837402
DOI: 10.1111/cge.14571 -
Dialogues in Clinical Neuroscience 2024Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a multifaceted etiology. This case report explores the ischemic cryptogenic vascular... (Review)
Review
INTRODUCTION
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a multifaceted etiology. This case report explores the ischemic cryptogenic vascular dissection as a potential underlying cause of ASD.
METHODS
A 9-year-old child presented with symptoms of ASD, including social interaction difficulties, repetitive behaviors, and cognitive challenges. Despite conventional ASD treatments, significant improvement was only observed after addressing an underlying ischemic cryptogenic vascular dissection identified through DCE-CT.
RESULTS
Following a reconstructive treatment approach to the vascular dissection, the patient showed marked improvement in cognitive functions, social abilities, and a reduction in ASD-related symptoms whether during the perioperative period or during approximately 5-month follow-up.
CONCLUSION
This case suggests that ischemic cryptogenic vascular dissection may contribute to the symptoms of ASD. Identifying and treating underlying vascular anomalies may offer a new avenue for mitigating ASD symptoms, emphasizing the need for comprehensive diagnostic estimations in ASD management.
Topics: Humans; Autism Spectrum Disorder; Child; Male; Microcephaly
PubMed: 38829782
DOI: 10.1080/19585969.2024.2359918