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.

Distinguishing multicystic from focal encephalomalacia on delayed MRI in children with term hypoxic ischemic injury.

Background And Purpose: To define cystic patterns resulting from term hypoxic ischemic injury (HII) on delayed Magnetic Resonance Imaging (MRI) and determine associated HII patterns and lesions that reflect the severity of injury, from a database of African children with cerebral palsy.

Methods: Retrospective review of 1175 children with cerebral palsy due to term HII diagnosed on late MRI, identifying those with cystic changes. These were classified as multicystic or (multi-) focal-cystic, and were evaluated for associated injuries-thalami, basal ganglia, hippocampi, cerebellum, and presence of ulegyria.

Heterozygous nonsense variants in the ferritin heavy-chain gene FTH1 cause a neuroferritinopathy.

Ferritin, the iron-storage protein, is composed of light- and heavy-chain subunits, encoded by FTL and FTH1, respectively. Heterozygous variants in FTL cause hereditary neuroferritinopathy, a type of neurodegeneration with brain iron accumulation (NBIA). Variants in FTH1 have not been previously associated with neurologic disease.

Expansion of clinical and variant spectrum of EEF2-related neurodevelopmental disorder: Report of two additional cases.

Eukaryotic translation elongation factor 2 (eEF2), encoded by the gene EEF2, is an essential factor involved in the elongation phase of protein translation. A specific heterozygous missense variant (p.P596H) in EEF2 was originally identified in association with autosomal dominant adult-onset spinocerebellar ataxia-26 (SCA26).

Heterozygous Nonsense Variants in the Ferritin Heavy Chain Gene Cause a Novel Pediatric Neuroferritinopathy.

Ferritin, the iron storage protein, is composed of light and heavy chain subunits, encoded by and , respectively. Heterozygous variants in cause hereditary neuroferritinopathy, a type of neurodegeneration with brain iron accumulation (NBIA). Variants in have not been previously associated with neurologic disease.

Acquired hump of the corpus callosum: a rare morphologic complication after CSF shunting.

Purpose: To present the longitudinal MR imaging of 4 children with an acquired corpus callosum hump, in order to demonstrate graphically that this represents a dysmorphology caused through a constellation of pre-existing pathology, timing, and complications of treatment.

Materials And Methods: Four cases with a corpus callosum hump were evaluated for common findings in the clinical history and on MRI scans. Those patients with available follow-up imaging were specifically evaluated for the presence of the hump on initial neonatal imaging and for evidence of development and progression of the deformity over time.

Magnetic resonance imaging protocols in pediatric stroke.

Neuroimaging protocols play an important role in the timely evaluation and treatment of pediatric stroke and its mimics. MRI protocols for stroke in the pediatric population should be guided by the clinical scenario and neurologic examination, with consideration of age, suspected infarct type and underlying risk factors. Acute stroke diagnosis and causes in pediatric age groups can differ significantly from those in adult populations, and delay in stroke diagnosis among children is a common problem.