No abstract available.
Ataxia* ; Atrophy* ; Cerebellar Ataxia ; Spinocerebellar Ataxias*

Spinocerebellar ataxia type 8 (SCA8), originally described in a family characterized by pure cerebellar ataxia, is caused by the expansion of combined CTA/CTG repeats on chromosome 13q21. We experienced a 26-year-old man who presented with a 10-years history of slowly progressive gait ataxia, dysarthria and blepharospasm. We performed genetic studies for SCA1, 2, 3, 6, 7 and 8, and detected CTA/CTG repeat expansion in the SCA8 gene. We now report the first Korean familial case of SCA8 confirmed by genetic study.
Adult ; Blepharospasm ; Cerebellar Ataxia ; Dysarthria ; Gait Ataxia ; Humans ; Spinocerebellar Ataxias*

BACKGROUND AND PURPOSE: Autosomal recessive cerebellar ataxias constitute a highly heterogeneous group of neurodegenerative disorders. This study was carried out to determine the clinical and genetic causes of ataxia in two families from Pakistan. METHODS: Detailed clinical investigations were carried out on probands in two consanguineous families. Magnetic resonance imaging was performed. Exome sequencing data were examined for likely pathogenic variants. Candidate variants were checked for cosegregation with the phenotype using Sanger sequencing. Public databases including ExAC, GnomAD, dbSNP, and the 1,000 Genome Project as well as ethnically matched controls were checked to determine the frequencies of the alleles. Conservation of missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. RESULTS: Reverse phenotyping identified spinocerebellar ataxia, autosomal recessive 1 [OMIM 606002, also referred to as ataxia oculomotor apraxia type 2 (AOA2)] and ataxia telangiectasia (OMIM 208900) in the two families. A novel homozygous missense mutation c.202 C>T (p.Arg68Cys) was identified within senataxin, SETX in the DNA of both patients in one of the families with AOA2. The patients in the second family were homozygous for a known variant in ataxia-telangiectasia mutated (ATM) gene: c.7327 C>T (p.Arg2443Ter). Both variants were absent from 100 ethnically matched control chromosomes and were either absent or present at very low frequencies in the public databases. CONCLUSIONS: This report extends the allelic heterogeneity of SETX mutations causing AOA2 and also presents an asymptomatic patient with a pathogenic ATM variant.
Alleles ; Apraxias* ; Ataxia Telangiectasia ; Ataxia* ; Cerebellar Ataxia ; DNA ; Exome ; Genome ; Humans ; Magnetic Resonance Imaging ; Movement Disorders ; Mutation, Missense ; Neurodegenerative Diseases ; Pakistan ; Phenotype ; Population Characteristics ; Spinocerebellar Ataxias ; Vertebrates

The spinocerebellar ataxia are a heterogeneous group of neurodegeneative disorders varying in both clinical manifestations and mode of inheritance. Recently, CAG trinucleotide repeats have been identified in inherited neurodegenerative disease such as dentrorubopallidoluysian atrophy, spinocerebellar ataxia type 1 (SCA1), Machado-Joseph disease (MJD) and SCA3. Individuals with SCA3 are phenotypically similar to those with SCA1 and, like MJD, the locus is linked to genetic markers on chromosome 14q24.3-qter. We experienced 38 year old man who presented with slowly progressive cerebellar dysfunction. Family history was not remarkable. We could not observe orofacial fasciculation, ophthalmoplegia, optic atrophy, peripheral neuropathy, amyotrophy, or dystonia. We peformed genomic polymerase chain reaction (PCR) analysis with patient's blood samples using the following primers: MJD52 (5'-CCAGTGAC TACTTTGATTCG-3') and MJD25 (3'-AAGTGTAGGTACACTTTCCGGT-5'). We found that his gene contained expanded CAG repeats (CAG repeat number was 69). We reported a clinically suspected sporadic case of genetically confirmed SCA3 who shared a similar genetic mutation with MJD and similar clinical presentation with SCA1. To our knowledge, this is the first case report on SCA3 in Korea. We think that the further genetic study with his family members should be done to evaluate mode of inheritance in this case.
Adult ; Ataxia ; Cerebellar Diseases ; Dystonia ; Fasciculation ; Genetic Markers ; Humans ; Korea ; Machado-Joseph Disease* ; Neurodegenerative Diseases ; Ophthalmoplegia ; Optic Atrophy ; Peripheral Nervous System Diseases ; Polymerase Chain Reaction ; Spinocerebellar Ataxias* ; Trinucleotide Repeats ; Wills*

Cerebellar degeneration is a group of diseases that manifests as progressive ataxia, that finally led to death without specific treatment. We report here two patients with cerebellar degeneration, who had shown an improvement and less progressive course, which is associated with panax ginseng intake. Patient 1 was a 60-year-old woman with multisystem atrophy (MSA) type C with 5 year history of ginseng ingestion. Patient 2 was a 54-year-old woman with spinocerebellar ataxia (SCA) type 6, who had a history of ginseng intake for 30 months. Both the patients showed atrophic change in the cerebellum by brain magnetic resonance imaging. Cerebellar functions had been semi-quantified by International Cooperative Ataxia Rating Scale (ICARS) and monitored before and after the ginseng ingestion every 6 to 12 months. In Patient 1 with MSA type C, ICARS had improved from 21 to 17.5 ± 1.8 in the following 5 years. In Patient 2 with SCA, ICARS also showed an improvement from 22 to 6.0 ± 1.0 over 30 months. However, when she stopped taking ginseng, it progressed up to 13 points in two years. These observations provide a potential disease-modifying effect of ginseng on patients with cerebellar degeneration.
Cerebellar Ataxia ; Cerebellar Diseases

The possibility of a central origin should be considered for late-onset concomitant esotropia. Concomitant esotropia has been reported to occur with spinocerebellar ataxia types 1, 2, and 3, but not with other degenerative cerebellar ataxia disorders. We report on a 28-year-old woman with ataxia in whom a detailed ophthalmologic examination revealed concomitant esotropia. She was subsequently diagnosed with dentatorubropallidoluysian atrophy (DRPLA). We suggest that the presence of concomitant esotropia could be used to differentiate DRPLA from other hereditary ataxias.
Adult ; Ataxia ; Atrophy ; Cerebellar Ataxia ; Esotropia ; Female ; Humans ; Spinocerebellar Ataxias ; Spinocerebellar Degenerations

The spinocerebellar ataxia type 7 is an autosomal dominant neurodegenerative disorder with expansion of unstable CAG trinucleotide repeats in a gene on chromosome 3p, and is classified as autosomal dominant cerebellar ataxia type II. Extrapyramidal findings are uncommonly recognized in autosomal dominant cerebellar ataxia type II. A 27-year-old woman showed progressive ataxia, visual disturbance and torticollis. We report a case of genetically confirmed spinocerebellar ataxia type 7 with extrapyramidal finding.
Adult ; Ataxia ; Cerebellar Ataxia ; Female ; Genes, vif ; Humans ; Neurodegenerative Diseases ; Spinocerebellar Ataxias* ; Torticollis* ; Trinucleotide Repeats

Patients with recurrent vertigo/dizziness or unsteadiness are a heterogeneous group of complex disorders affecting the peripheral and central vestibular system. They represent a diagnostic challenge for the clinicians, and their genetic basis is largely not known. However, there are some cerebellar and vestibular disorders with a strong genetic background, such as episodic ataxia, spinocerebellar ataxia, vestibular migraine, Meniere's disease, and autosomal dominant nonsyndromic deafness. Furthermore, recent advances in next generation sequencing technique are increasing the number of novel genes associated with cerebellar and vestibular disorders. In this article, we have summarized clinical and molecular genetics findings in neuro-otology.
Ataxia ; Cerebellar Ataxia ; Deafness ; Dizziness ; Humans ; Meniere Disease ; Migraine Disorders ; Molecular Biology ; Neurotology ; Spinocerebellar Ataxias

BACKGROUND AND PURPOSE: The etiologies and frequencies of cerebellar ataxias vary between countries. Our primary aim was to determine the frequency of each diagnostic group of cerebellar ataxia patients in a Korean population. METHODS: We reviewed the medical records of patients who were being followed up between November 1994 and February 2016. We divided patients with cerebellar ataxias into familial and non-familial groups and analyzed the frequency of each etiology. Finally, we categorized patients into genetic, sporadic, secondary, and suspected genetic, but undetermined ataxia. RESULTS: A total of 820 patients were included in the study, among whom 136 (16.6%) familial patients and 684 (83.4%) non-familial cases were identified. Genetic diagnoses confirmed 98/136 (72%) familial and 72/684 (11%) nonfamilial patients. The overall etiologies of progressive ataxias comprised 170 (20.7%) genetic, 516 (62.9%) sporadic, 43 (5.2%) secondary, and 91 (11.1%) undetermined ataxia. The most common cause of ataxia was multiple-system atrophy (57.3%). In the genetic group, the most common etiology was spinocerebellar ataxia (152/170, 89.4%) and the most common subtype was spinocerebellar ataxia-3.38 of 136 familial and 53 of 684 sporadic cases (91/820, 11.1%) were undetermined ataxia. CONCLUSIONS: This is the largest epidemiological study to analyze the frequencies of various cerebellar ataxias in a Korean population based on the large database of a tertiary hospital movement-disorders clinic in South Korea. These data would be helpful for clinicians in constructing diagnostic strategies and counseling for patients with cerebellar ataxias.
Ataxia ; Atrophy ; Cerebellar Ataxia* ; Counseling ; Diagnosis ; Epidemiologic Studies ; Friedreich Ataxia ; Humans ; Korea ; Medical Records ; Spinocerebellar Ataxias ; Tertiary Care Centers

Dominantly inherited spinocerebellar ataxias (SCAs) are a group of the heterogenous neurodegenerative diseases that are characterized by chronic progressive cerebellar ataxia associated with various combinations of other neurological signs. Clinical classification is difficult because of the phenotypic overlap. With the evolution of molecular genetics, the loci and mutations for many of the ataxias have been identified, allowing more definitive molecular classification. We experienced 42 years-old man who presented with progressive both lower leg weakness, dysarthria, ataxia, ophthalmoplegia, and nystagmus. The family history was remarkably suspicious. We could not observe the upper extremity weakness, definite evidences of peripheral neuropathy and myopathy in electrodiagnosis. No abnormal findings in blood chemistry and brain MRI. We performed polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) analysis, found that his gene contained expanded CAG repeats (CAG repeat number was 72). Although no effective treatment exists for most the ataxic syndromes, the accurate diagnosis and the genetic counseling are often important to the patient's family for prognostication.
Adult ; Ataxia ; Brain ; Cerebellar Ataxia ; Chemistry ; Classification ; Diagnosis ; Dysarthria ; Electrodiagnosis ; Electrophoresis, Polyacrylamide Gel ; Genetic Counseling ; Humans ; Leg ; Machado-Joseph Disease* ; Magnetic Resonance Imaging ; Molecular Biology ; Muscular Diseases ; Neurodegenerative Diseases ; Ophthalmoplegia ; Peripheral Nervous System Diseases ; Polymerase Chain Reaction ; Spinocerebellar Ataxias* ; Upper Extremity