A programmed decline in ribosome levels governs human early neurodevelopment.

Many neurodevelopmental defects are linked to genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. How reductions in ribosome biogenesis can result in tissue- and developmental-specific defects remains unclear. Here we describe variants in the ribosome biogenesis factor AIRIM/C1orf109 that are primarily associated with neurodevelopmental disorders.

Central Dysmyelination in SSADH-Deficient Humans and Mice.

Objectives: Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder characterized by an accumulation of γ-aminobutyric (GABA). In addition to its synaptic role as an inhibitory neurotransmitter, GABA also plays an important role in myelination. We aimed to investigate the relationship between GABA and myelination abnormalities in SSADHD patients and the mouse model.

Neuroimaging patterns in patients with mitochondrial leukoencephalopathies.

Background And Objectives: Leukoencephalopathies are characterized by white matter (WM) abnormalities and include various primary mitochondrial diseases (MD) that impact mitochondrial function across all neuroglial cells. Understanding these associations is vital for effective clinical management.

Methods: We performed a retrospective analysis of patients with genetically confirmed MD who exhibited white matter abnormalities at a pediatric academic medical center.

ELFN1 deficiency: The mechanistic basis and phenotypic spectrum of a neurodevelopmental disorder with epilepsy.

Purpose: Synaptic communication deficits are central to many neurodevelopmental disorders. However, for rare monogenic conditions, these disorders remain poorly defined, with limited understanding of their molecular etiology. A homozygous frameshift variant in the synaptic cell adhesion molecule ELFN1 was reported in a family with 3 affected siblings with epileptic encephalopathy, alongside a missense variant of uncertain significance in a cohort study involving a family with intellectual disability.

Pediatric-type diffuse low-grade gliomas with MYB alterations: Neuroimaging of the Diffuse astrocytomas, or -altered.

Background And Purpose: Diffuse astrocytoma, MYB or MYBL1-altered is a new tumor type in the family of Pediatric-type diffuse low-grade gliomas and genetically related to angiocentric glioma. Imaging features of Diffuse astrocytoma, MYB or MYBL1-altered are less well known. During our clinical work, we identified a relatively characteristic imaging pattern in a subset of our patients consisting of a large, diffuse hemispheric tumor with displaced central vessels which we termed the "fireworks sign".

Variable Flip Angle Optimization for Fetal Brain Imaging With Reduced Specific Absorption Rate.

Half-Fourier Acquisition with Single-Shot Turbo Spin Echo (HASTE) scans are routinely used for fetal brain imaging, but they have a high specific absorption rate (SAR) and can be inefficient due to SAR limits. Here, we have designed an optimized variable flip angle (VFA) pattern for fetal HASTE neuroimaging to reduce both the SAR and repetition time (TR) of the HASTE sequence while maintaining similar image quality to standard fetal HASTE imaging with a constant flip angle (CFA). The VFA pattern was optimized by minimizing the difference in expected signal between the VFA and CFA scans while constraining the SAR of the VFA scan to no more than 65% of the SAR of the CFA scan and reducing the TR by 29%.

MAPK Signaling and Angiopoietin-2 Contribute to Endothelial Permeability in Capillary Malformations.

Unlabelled: Capillary malformations (CM) are slow-flow vascular abnormalities present at birth and predominantly manifest as cutaneous lesions. In the rare neurocutaneous disorder known as Sturge Weber Syndrome (SWS), individuals exhibit CM not only on the skin but also within the leptomeninges of the brain and the choroid of the eye. >90% of CM are caused by a somatic R183Q mutation in the gene encoding Gαq - a heterotrimeric G-protein subunit.

Single Large-Scale Mitochondrial Deletion Syndromes: Neuroimaging Phenotypes and Longitudinal Progression in Pediatric Patients.

Background And Purpose: Single large-scale mitochondrial deletion syndrome (SLSMD) comprises devastating mitochondrial diseases often classified into 3 major clinical syndromes: Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), and Pearson syndrome (PS). Nevertheless, there remains large clinical variability and overlap among these SLSMD groups. Therefore, further stratification is required for more precise prognostication and clinical management.

Biallelic variants in encoding a subunit of the TFIIIC2 complex are associated with neurodevelopmental phenotypes in humans and zebrafish.

RNA polymerase III transcribes essential non-coding RNAs, a process regulated by transcription factors TFIIIB and TFIIIC. Although germline variants in TFIIIC subunit genes have been described in a few patients with neurodevelopmental disorders, the associated pathogenesis and clinical spectrum are not yet well defined. Herein, we describe the identification of biallelic variants in which encodes a key component of the TFIIIC subunit, in four patients from three unrelated families of different ethnicities collected through GeneMatcher.

Magnetic resonance imaging findings in SCN1A-related epilepsies and Dravet syndrome: A systematic review.

We systematically reviewed the literature on neuroimaging findings in Dravet syndrome (DS) and SCN1A-related epilepsies to classify the reported structural abnormalities observed on magnetic resonance imaging (MRI). We searched PubMed and MEDLINE from January 2000 to June 2024 for studies describing brain MRI findings in DS and SCN1A-related epilepsies through specific keywords and MeSH (Medical Subject Headings) terms. Duplicates were removed, and titles and abstracts were screened.

Overview of neuroimaging in primary mitochondrial disorders.

Advancements in understanding the clinical, biochemical, and genetic aspects of primary mitochondrial disorders, along with the identification of a broad range of phenotypes frequently involving the central nervous system, have opened a new and crucial area in neuroimaging. This expanding knowledge presents significant challenges for radiologists in clinical settings, as the neuroimaging features and their associated metabolic abnormalities become more complex. This review offers a comprehensive overview of the key neuroimaging features associated with the common primary mitochondrial disorders.

Frontal Paraventricular Cysts: Refined Definitions and Outcomes.

Background And Purpose: Frontal paraventricular cystic changes have a varied etiology that includes connatal cysts, subependymal pseudocysts, necrosis, and enlarged perivascular spaces. These may be difficult to distinguish by neuroimaging and have a variety of associated prognoses. We aim to refine the neuroimaging definition of frontal horn cysts and correlate it with adverse clinical conditions.

Frequency and Distribution of Perinatal Arterial Ischemic Stroke in a Cohort of Patients With Cerebral Palsy Using Delayed MRI.

Purpose: This study examined the occurrence and MRI characteristics of perinatal arterial ischemic stroke (PAIS) in children with cerebral palsy (CP) and suspected term hypoxic-ischemic injury (HII).

Methods: A retrospective review of brain MRI scans was conducted on children with CP and suspected term HII in South Africa.

Results: Out of 1620 children with CP included in the study, 15 (0.

Clinical and neuroradiological spectrum of biallelic variants in NOTCH3.

Background: NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. NOTCH3 variants are the leading cause of hereditary cerebral small vessel disease (SVD). While monoallelic cysteine-involving missense variants in NOTCH3 are well-studied in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), patients with biallelic variants in NOTCH3 are extremely rare and not well characterised.

Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells.

Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency.

Background And Objectives: Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of mitochondrial metabolism that is caused by pathogenic variants in multiple genes, including . Typical neonatal brain imaging findings have been described, with a focus on malformative and encephaloclastic features. Fetal brain MRI in PDCD has not been comprehensively described.

Approaches to supratentorial brain tumours in children.

The differential diagnosis of supratentorial brain tumours in children can be challenging, especially considering the recent changes to the WHO classification of CNS tumours published in 2021. Many new tumour types have been proposed which frequently present in children and young adults and their imaging features are currently being described by the neuroradiology community. The purpose of this article is to provide guidance to residents and fellows new to the field of paediatric neuroradiology on how to evaluate an MRI of a patient with a newly diagnosed supratentorial tumour.

Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study.

Purpose: Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome.

Characteristic Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency.

Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of mitochondrial metabolism that is caused by pathogenic variants in multiple genes, including . Typical neonatal brain imaging findings in PDCD have been described, with a focus on malformative features and chronic encephaloclastic changes. However, fetal brain MRI imaging in confirmed PDCD has not been comprehensively described.

Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia.

Background: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3).

Objectives: We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients.

Methods: We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years.

Biallelic variants in GTF3C5, a regulator of RNA polymerase III-mediated transcription, cause a multisystem developmental disorder.

General transcription factor IIIC subunit 5 (GTF3C5) encodes transcription factor IIIC63 (TFIIIC63). It binds to DNA to recruit another transcription factor, TFIIIB, and RNA polymerase III (Pol III) to mediate the transcription of small noncoding RNAs, such as tRNAs. Here, we report four individuals from three families presenting with a multisystem developmental disorder phenotype with biallelic variants in GTF3C5.

Loss of symmetric cell division of apical neural progenitors drives -related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) are a heterogenous group of epilepsies in which altered brain development leads to developmental delay and seizures, with the epileptic activity further negatively impacting neurodevelopment. Identifying the underlying cause of DEEs is essential for progress toward precision therapies. Here we describe a group of individuals with biallelic variants in and determine that variant type is correlated with disease severity.

Advancing the neuroimaging diagnosis and understanding of mitochondrial disorders.

Mitochondrial diseases, a diverse and intricate group of disorders, result from both nuclear DNA and mitochondrial DNA malfunctions, leading to a decrease in cellular energy (ATP) production. The increasing understanding of molecular, biochemical, and genetic irregularities associated with mitochondrial dysfunction has led to a wider recognition of varying mitochondrial disease phenotypes. This broadening landscape has led to a diverse array of neuroimaging findings, posing a challenge to radiologists in identifying the extensive range of possible patterns.

Frequency of Cerebellar Abnormalities Associated With the Differing Magnetic Resonance Imaging Patterns of Term Hypoxic-Ischemic Injury in Children.

Background: We aimed to determine the frequency of cerebellar injury using delayed magnetic resonance imaging (MRI) in children with cerebral palsy, diagnosed with term hypoxic-ischemic injury (HII), and to characterize this for the different MRI patterns of HII.

Methods: We retrospectively reviewed delayed MRI scans in children with cerebral palsy, of whom 1175 had term HII. The pattern of HII was classified into basal ganglia-thalamus (BGT) pattern, watershed (WS) pattern, combined BGT/WS, and multicystic HII.