OBJECTIVE: To explore the clinical and genetic features of a child with Pontocerebellar hypoplasia type 2B (PCH2B) due to compound heterozygous variants of the TSEN2 gene. METHODS: A PCH2B patient presented at Department of Pediatric Neurology, Xiangya Hospital of Central South University in June 2023 was selected as the study subject. Clinical data of the patient were retrospectively analyzed. The patient and her parents were subjected to whole exome sequencing and bioinformatic analysis. Pathogenicity of the candidate variants were classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also conducted by searching the China National Knowledge Infrastructure (CNKI), Wanfang Data, and PubMed databases from their establishment to May 2025 using keywords "TSEN2 gene" "PCH2B" and "Pontocerebellar Hypoplasia 2B" to summarize the clinical and genotypic features of patients with PCH2B due to variants of the TSEN2 gene. This study was approved by the Medical Ethics Committee of the Hospital (No.: #202310892). RESULTS: The patient, a 6-year-5-month-old girl, had exhibited severe global developmental delay, developmental regression, autism spectrum disorder, myoclonus of eyelids, feeding difficulty, irritability, progressive microcephaly, esotropia, and hypotonia. MRI showed reduced volume of bilateral cerebellar hemispheres and vermis. Genetic testing revealed that she has harbored compound heterozygous variants of the TSEN2 gene (NM_025265.4), namely c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile), which were inherited from her father and mother, respectively. Both variants were classified as likely pathogenic based on the ACMG guidelines and were previously unreported. Literature review has identified six PCH2B patients with missense, nonsense, frameshift, and splice site variants of the TSEN2 gene. Their main clinical manifestations included global developmental delay, progressive microcephaly, feeding difficulties, irritability, and vermis hypoplasia. Cranial MRI and genetic testing are crucial for definite diagnosis. CONCLUSION The c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile) compound heterozygous variants of the TSEN2 gene probably underlay the pathogenesis in this patient. Above findings has expanded the genotypic and phenotypic spectra of TSEN2-related PCH2B, and offered guidance for genetic counseling for this family.
Child ; Female ; Humans ; Cerebellar Diseases/genetics* ; Exome Sequencing ; Heterozygote ; Mutation

OBJECTIVE: To explore the genetic etiology of Pontocerebellar Hypoplasia Type 2D (PCH2D) due to compound heterozygous variants of the SEPSECS gene and to conduct a literature review. METHODS: A child with PCH2D diagnosed at the Children's Hospital of Nanjing Medical University due to "motor and cognitive retardation" in June 2022 was selected as the study subject. Clinical and imaging data were collected. Genomic DNA was extracted from the peripheral blood samples of the child and her parents. Whole-exome sequencing (WES) was conducted using capture-based high-throughput sequencing technology. Candidate variants were confirmed by Sanger sequencing and bioinformatics analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG). Additionally, relevant literature on PCH2D caused by SEPSECS gene variants was reviewed to assess the genotype-phenotype correlation. This study was approved by the Medical Ethics Committee of the hospital (Ethical No.: 202402022-1). RESULTS: The child, a 1-year-and-3-month-old girl, had presented with global developmental delay, progressive microcephaly, hypotonia, elevated blood lactic acid, feeding difficulties, and absent tendon reflexes. Cranial MRI indicated thinning of the splenium of the corpus callosum. Electromyography suggested peripheral neurogenic changes primarily affecting sensory nerves. WES revealed the she has harbored compound heterozygous variants of the SEPSECS gene, namely c.194A>G (p.N65S) and c.896_c.897insA (p.N299fs*2) (NM_016955), which were inherited from her father and mother, respectively. Neither of her parents had related clinical manifestations. According to the ACMG guidelines, the c.194A>G (p.N65S) variant was classified as pathogenic (PM1+PM2_Supporting+PM3+PP3), and the c.896_c.897insA (p.N299fs*2) variant was as likely pathogenic (PVS1+PM2_Supporting). A total of 18 relevant literature were retrieved, which have involved 32 patients (including this case). The p.N65S variant has been reported previously, while the p.N299fs*2 variant is novel. CONCLUSION Compound heterozygous variants in the SEPSECS gene probably underlay the pathogenesis of PCH2D in this child. Above finding has expanded the mutational and phenotypic spectrum of the SEPSECS gene.
Humans ; Female ; Infant ; Heterozygote ; Cerebellar Diseases/genetics* ; Membrane Proteins/genetics* ; Exome Sequencing ; Mutation

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

There have been several reports of patients with isolated lesions of the cerebellar vermis presenting with clinical features similar to those of peripheral vestibulopathy. We report a case of small, isolated hematoma in the cerebellar vermis in a patient who presented with vertigo, ipsilesional nystagmus, and body lateropulsion to the contralesional side without the usual signs or symptoms of cerebellar dysfunction. Although they present with symptoms that mimic those of peripheral vestibulopathy, and brain computed tomography shows no abnormality, as there may be a small, isolated hematoma or infarction in the cerebellar vermis. Thus, brain magnetic resonance imaging should be performed in elderly patients with vascular risk factors.
Aged ; Brain ; Cerebellar Diseases ; Cerebellar Vermis ; Hematoma ; Hemorrhage ; Humans ; Infarction ; Magnetic Resonance Imaging ; Risk Factors ; Vertigo

Abnormal eye movements are commonly observed in movement disorders. Ocular motility examination should include bedside evaluation and laboratory recording of ocular misalignment, involuntary eye movements, including nystagmus and saccadic intrusions/oscillations, triggered nystagmus, saccades, smooth pursuit (SP), and the vestibulo-ocular reflex. Patients with Parkinson's disease (PD) mostly show hypometric saccades, especially for the self-paced saccades, and impaired SP. Early vertical saccadic palsy is characteristic of progressive supranuclear palsy-Richardson's syndrome. Patients with cortico-basal syndrome typically show a delayed onset of saccades. Downbeat and gaze-evoked nystagmus and hypermetric saccades are characteristic ocular motor findings in ataxic disorders due to cerebellar dysfunction. In this review, we discuss various ocular motor findings in movement disorders, including PD and related disorders, ataxic syndromes, and hyperkinetic movement disorders. Systemic evaluation of the ocular motor functions may provide valuable information for early detection and monitoring of movement disorders, despite an overlap in the abnormal eye movements among different movement disorders.
Ataxia ; Cerebellar Diseases ; Eye Movements ; Humans ; Hyperkinesis ; Movement Disorders ; Paralysis ; Parkinson Disease ; Parkinsonian Disorders ; Pursuit, Smooth ; Reflex, Vestibulo-Ocular ; Saccades

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), which is caused by mutations in SACS gene, is a very rare neurodegenerative disorder characterized by the clinical triad of early onset cerebellar ataxia, pyramidal tract features, and sensorimotor polyneuropathy. Herein, we report a 35-year-old Korean male who presented with gait disturbance and lower extremity weakness. Neuroimaging and ophthalmologic evaluation revealed features consistent with ARSACS. Mutation in SACS gene was demonstrated in clinical exome sequence analysis and the patient was finally diagnosed as ARSACS.
Adult ; Ataxia ; Cerebellar Ataxia ; Exome ; Gait ; Humans ; Lower Extremity ; Male ; Muscle Spasticity ; Neurodegenerative Diseases ; Neuroimaging ; Polyneuropathies ; Pyramidal Tracts ; Sequence Analysis ; Spinocerebellar Degenerations

Genetic prion diseases account for about 10-15% of all cases of human prion disease and are caused by mutations in the prion protein gene. Gerstmann-Sträussler-Scheinker (GSS) disease is a rare genetic prion disease, which is characterized by slowly progressive cerebellar ataxia and the occurrence of cognitive decline in the later stage. P102L is the most common mutation in GSS. We report a patient with a P102L mutation that initially manifested as rapidly progressive dementia without cerebellar symptoms.
Cerebellar Ataxia ; Creutzfeldt-Jakob Syndrome ; Dementia ; Gerstmann-Straussler-Scheinker Disease ; Humans ; Prion Diseases ; Prions

Superficial siderosis (SS) of the central nervous system is a rare disease, which is caused by the accumulation of iron from the hemoglobin in the superficial layer of the brain, spinal cord, and central parts of cranial nerves. The etiology of SS is the accumulation of hemosiderin in the subarachnoid space due to chronic or repeated hemorrhage resulting in progressive and irreversible neurological dysfunction. The cause of the disease is aneurysm, trauma, tumor, and vascular malformation. In most cases, the cause of bleeding is unknown. Clinical features include sensorineural hearing loss, cerebellar ataxia, and myelopathy. Until now, magnetic resonance imaging (MRI) has only been diagnosed and there is no standardized treatment. We will investigate clinical features and MRI findings of SS disease in the central nervous system using 2 patient cases.
Aneurysm ; Brain ; Central Nervous System ; Cerebellar Ataxia ; Cranial Nerves ; Dizziness ; Hearing Loss, Sensorineural ; Hemorrhage ; Hemosiderin ; Humans ; Iron ; Magnetic Resonance Imaging ; Rare Diseases ; Siderosis ; Spinal Cord ; Spinal Cord Diseases ; Subarachnoid Space ; Vascular Malformations ; Vertigo

PURPOSE: To report a case of toxic optic neuropathy caused by chlorfenapyr ingestion accompanied by central nervous system involvement. CASE SUMMARY: A 44-year-old female visited our clinic complaining of reduced visual acuity in both eyes for 7 days. She had ingested a mouthful of chlorfenapyr for a suicide attempt 2 weeks prior to the visit. Gastric lavage was performed immediately after ingestion at the other hospital. Her best-corrected visual acuity was finger count 30 cm in the right eye and hand motion in the left eye. Both pupils were dilated by 5.0 mm and the response to light was sluggish in both eyes. A relative afferent pupillary defect was detected in her left eye. Funduscopy revealed optic disc swelling in both eyes. Magnetic resonance imaging of the brain showed a symmetric hyper-intense signal in the white matter tract including the internal capsule, corpus callosum, middle cerebellar peduncle, and brainstem. The patient was diagnosed with toxic optic neuropathy induced by chlorfenapyr ingestion, and underwent high-dose intravenous corticosteroid pulse therapy. Three days later, the best-corrected visual acuity was no light perception in both eyes. Three months later, optic atrophy was observed in both eyes. Optical coherence tomography revealed a reduction in the thicknesses of the retinal nerve fiber layer and ganglion cell and inner plexiform layer in the macular area. CONCLUSIONS: Ingestion of even a small amount of chlorfenapyr can cause severe optic nerve damage through the latent period, despite prompt lavage and high-dose steroid treatment.
Adult ; Brain ; Brain Stem ; Central Nervous System ; Corpus Callosum ; Eating ; Female ; Fingers ; Ganglion Cysts ; Gastric Lavage ; Hand ; Humans ; Internal Capsule ; Magnetic Resonance Imaging ; Middle Cerebellar Peduncle ; Mouth ; Nerve Fibers ; Optic Atrophy ; Optic Nerve ; Optic Nerve Diseases ; Poisoning ; Pupil ; Pupil Disorders ; Retinaldehyde ; Suicide ; Therapeutic Irrigation ; Tomography, Optical Coherence ; Visual Acuity ; White Matter

BACKGROUND: Cerebellum has an important role in sensorimotor control including speech. Multiple system atrophy (MSA) is a sporadic and rapidly progressive neurodegenerative disorder that presents with autonomic failure in combination with Parkinsonism or cerebellar ataxia. CASE REPORT: We report a case of MSA-cerebellum subtype associated with emergence of irreversible explosive speech following olanzapine therapy. CONCLUSIONS: Further investigation into speech problems in MSA according to subtype and disease severity is needed, and side effects of olanzapine therapy should also be considered.
Antipsychotic Agents ; Cerebellar Ataxia ; Cerebellum ; Humans ; Multiple System Atrophy* ; Neurodegenerative Diseases ; Parkinsonian Disorders