Objective To investigate the role of specific imaging parameters in the clinical diagnosis and differential diagnosis of multiple system atrophy with predominant cerebellar ataxia （MSA-C）. Methods Imaging data including pontine volume were measured for 34 patients with MSA-C who were admitted to Department of Neurology， Shaanxi Provincial People’s Hospital， from January 2021 to October 2024， and these patients were compared with 9 patients with progressive supranuclear palsy （PSP）， 8 patients with spinocerebellar ataxia （SCA）， and 32 normal controls. Results There was a significant difference in pontine volume between the MSA-C group and the PSP group， as well as between the MSA-C group and the normal control group （P<0.008 3）， while there was no significant difference between the MSA-C group and the SCA group （P>0.008 3）. There was no significant difference in pontine volume between the PSP group and the SCA group and between the PSP group and the normal control group （P>0.008 3）， and there was a significant difference in pontine volume between the SCA group and the normal control group （P<0.008 3）. The receiver operating characteristic （ROC） curve analysis showed that pontine volume had a cut-off value of 8.66 cm3 in the diagnosis of MSA-C， with an area under the ROC curve （AUC） of 0.972， a sensitivity of 94.12%， and a specificity of 100%； pontine volume had a cut-off value of 8.66 cm3 in the differential diagnosis of MSA-C from PSP， with an AUC of 0.961， a sensitivity of 94.1%， and a specificity of 100%； pontine volume had a cut-off value of 6.79 cm3 in the differential diagnosis of MSA-C from SCA， with an AUC of 0.783， a sensitivity of 52.94%， and a specificity of 100%. Conclusion As the most objective indicator for evaluating pontine atrophy， pontine volume has a great significance in the diagnosis and differential diagnosis of MSA-C.
Ataxia

Dentatorubral-pallidoluysian atrophy（DRPLA） is a rare autosomal dominant neurodegenerative disease caused by CAG triplet expansion in the atrophin 1 （ATN1） gene. Up to now， the pathogenesis of DRPLA remains unclear. The main clinical features of DRPLA include myoclonus， epilepsy， ataxia， choreoathetosis， and cognitive impairment. DRPLA has great clinical heterogeneity， and the number of CAG repeats is negatively correlated with age of onset and disease severity. Some patients with late-onset DRPLA may have atypical manifestations without typical imaging changes， which brings challenges to the diagnosis of the disease. This article reviews the pathogenesis， pathological features， clinical and imaging manifestations， diagnosis， and potential treatment of DRPLA， in order to deepen the understanding of this disease.
Ataxia ; Myoclonus

Familial hemophagocytic lymphohistiocytosis （FHL） with central nervous system involvement as the initial clinical manifestation is very rare and has atypical clinical manifestations， which often leads to difficulties in early diagnosis and misdiagnosis. This article reports two cases of FHL confirmed by genetic testing in Department of Neurology， Women and Children’s Hospital of Qingdao University. One patient was a boy with 1‒3 years of age， while the other patient was a girl of pre-school age； both patients had the main clinical manifestations of unstable walking and dysarthria. Brain MRI findings of the boy suggested multiple abnormal signals in the bilateral hemispheres and the cerebellum， and brain MRI findings of the girl suggested multiple symmetrical hyperintensities in the bilateral frontal lobes， the periventricular region， and the basal ganglia. Both children were found to have PRF1 gene mutations. This article reviews relevant literature to improve the understanding of this disease among clinicians， and the possibility of this disease should be considered in case of unexplained central nervous system involvement. For suspected cases， it is recommended to conduct comprehensive examinations and genetic testing， so as to achieve early diagnosis， start treatment in a timely manner， and improve prognosis.
Ataxia

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.
Humans ; Child ; Female ; Cerebellar Ataxia/diagnosis* ; Talipes Cavus ; Hearing Loss, Sensorineural/diagnosis* ; Optic Atrophy/diagnosis* ; Mutation ; Phenotype ; Sodium-Potassium-Exchanging ATPase/genetics* ; Foot Deformities, Congenital ; Reflex, Abnormal

OBJECTIVE: To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS). METHODS: Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases. CONCLUSION The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.
Female ; Humans ; Heat-Shock Proteins/genetics* ; Muscle Spasticity/genetics* ; Mutation ; Spinocerebellar Ataxias/pathology* ; Child, Preschool

OBJECTIVE: To explore the genetic basis for a EAST/SeSAME syndrome child featuring epilepsy, ataxia, sensorineural deafness and intellectual disability. METHODS: A child with EAST/SeSAME syndrome who had presented at the Third Affiliated Hospital of Zhengzhou University in January 2021 was selected as the study object. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored compound heterozygous variants of the KCNJ10 gene, namely c.557T>C (p.Val186Ala) and c.386T>A (p.Ile129Asn), which were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted as likely pathogenic (PM1+PM2_Supporting+PP3+PP4; PM1+PM2_Supporting+PM3+PP3+PP4). CONCLUSION The patient was diagnosed with EAST/SeSAME syndrome due to the compound heterozygous variants of the KCNJ10 gene.
Humans ; Child ; Female ; Intellectual Disability/genetics* ; Hearing Loss, Sensorineural/genetics* ; Ataxia ; Genetic Diseases, X-Linked ; Mutation

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.
Humans ; Male ; Adult ; Female ; Xanthomatosis, Cerebrotendinous/pathology* ; Pedigree ; Cholestanetriol 26-Monooxygenase/genetics* ; Mutation ; Ataxia

OBJECTIVE: To explore the clinical and genetic characteristics of a child with spinocerebellar ataxia type 29 (SCA29) due to novel variant of the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) gene. METHODS: The child was subjected high-throughput sequencing, and candidate variant was verified by Sanger sequencing of his family members. RESULTS: The child was found to harbor a c.800C>T (p.T267M) variant of the ITPR1 gene, which was not found in his parents and their fetus. The variant has occurred in a hotspot of the ITPR1 gene variants and was unreported before in China. Based on his clinical and genetic characteristics, the child was diagnosed with SCA29. CONCLUSION The novel heterozygous c.800C>T (p.T267M) of the ITPR1 gene probably underlay the SCA29 in this child.
Child ; Humans ; Family ; Inositol 1,4,5-Trisphosphate Receptors/genetics* ; Mutation ; Spinocerebellar Ataxias/genetics* ; Spinocerebellar Degenerations

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare and early-onset neurodegenerative disease caused by variants of the SACS gene which maps to chromosome 13q11 and encodes sacsin protein. Sacsin is highly expressed in large motor neurons, in particular cerebellar Purkinje cells. This article has provided a review for the structure and function of sacsin protein and the mechanisms underlying abnormalities of sacsin in ARSACS disease.
Humans ; Spinocerebellar Ataxias/pathology* ; Ataxia/genetics* ; Muscle Spasticity/genetics*

OBJECTIVE: To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome. METHODS: An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS). RESULTS: The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother. CONCLUSION The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.
Humans ; Infant ; Male ; alpha-Thalassemia/diagnosis* ; Ataxia Telangiectasia Mutated Proteins/genetics* ; East Asian People ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/diagnosis* ; Pedigree ; X-linked Nuclear Protein/genetics*