Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of disorders. Current molecular classification corresponds to the order of gene description (SCA1-SCA 25). The prevalence of SCAs is estimated to be 1-4/100,000. Patients exhibit usually a slowly progressive cerebellar syndrome with various combinations of oculomotor disorders, dysarthria, dysmetria/kinetic tremor, and/or ataxic gait. They can present also with pigmentary retinopathy, extrapyramidal movement disorders (parkinsonism, dyskinesias, dystonia, chorea), pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioral symptoms), peripheral neuropathy. SCAs are also genetically heterogeneous and the clinical diagnosis of subtypes of SCAs is complicated by the salient overlap of the phenotypes between genetic subtypes. The following clinical features have some specific values for predicting a gene defect: slowing of saccades in SCA2, ophthalmoplegia in SCA1, SCA2 and SCA3, pigmentary retinopathy in SCA7, spasticity in SCA3, dyskinesias associated with a mutation in the fibroblast growth factor 14 (FGF 14) gene, cognitive impairment/behavioral symptoms in SCA17 and DRPLA, seizures in SCA10, SCA17 and DRPLA, peripheral neuropathy in SCA1, SCA2, SCA3, SCA4, SCA8, SCA18 and SCA25. Neurophysiological findings are compatible with a dying-back axonopathy and/or a neuronopathy. Three patterns of atrophy can be identified on brain MRI: a pure cerebellar atrophy, a pattern of olivopontocerebellar atrophy, and a pattern of global brain atrophy. A remarkable observation is the presence of dentate nuclei calcifications in SCA20, resulting in a low signal on brain MRI sequences. Several identified mutations correspond to expansions of repeated trinucleotides (CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA, CTG repeats in SCA8). A pentanucleotide repeat expansion (ATTCT) is associated with SCA10. Missense mutations have also been found recently. Anticipation is a main feature of SCAs, due to instability of expanded alleles. Anticipation may be particularly prominent in SCA7. It is estimated that extensive genetic testing leads to the identification of the causative gene in about 60-75 % of cases. Our knowledge of the molecular mechanisms of SCAs is rapidly growing, and the development of relevant animal models of SCAs is bringing hope for effective therapies in human.
Cerebellum 2005
PMID:The wide spectrum of spinocerebellar ataxias (SCAs). 1589 52

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders currently associated with 27 genes. The most frequent types are caused by expansions in coding CAG repeats. The frequency of SCA subtypes varies among populations. We examined the occurrence of rare SCAs, SCA8, SCA12, SCA17 and dentatorubro-pallidoluysian atrophy (DRPLA), in the Czech population from where the data were missing. We analyzed causal gene expansions in 515 familial and sporadic ataxic patients negatively tested for SCA1-3 and SCA6-7. Pathogenic SCA8 and SCA17 expansions were identified in eight and five patients, respectively. Tay-Sachs disease was later diagnosed in one patient with an SCA8 expansion and the diagnosis of multiple sclerosis (MS) was suspected in two other patients with SCA8 expansions. These findings are probably coincidental, although the participation of SCA8 expansions in the susceptibility to MS and disease progression cannot be fully excluded. None of the patients had pathogenic SCA12 or DRPLA expansions. However, three patients had intermediate SCA12 alleles out of the normal range with 36 and 43 CAGs. Amyotrophic lateral sclerosis (ALS) was probable in the patient with 43 CAGs. This coincidence is remarkable, especially in the context with the recently identified predisposing role of longer SCA2 alleles in ALS. Five families with SCA17 represent a significant portion of ataxic patients and this should be reflected in the diagnostics of SCAs in the Czech population. SCA8 expansions must be considered after careful clinical evaluation.
Cerebellum 2013 Apr
PMID:Spinocerebellar ataxias type 8, 12, and 17 and dentatorubro-pallidoluysian atrophy in Czech ataxic patients. 2287 68

Oculomotor abnormalities are common in the spinocerebellar ataxias (SCAs). In studies of SCAs 1, 2, 3, and 6, eye movement abnormalities correlate with disease severity. Oculomotor abnormalities may be the sole motor manifestation of early and/or premanifest disease; however, not all ataxia rating scales include oculomotor assessment. We sought to identify the prevalence and characteristics of oculomotor abnormalities at first presentation in a large SCA cohort, including those in earlier stages of disease. We performed a retrospective assessment of initial clinical examinations of SCA patients followed in the Massachusetts General Hospital Ataxia Unit and assessed with the Brief Ataxia Rating Scale (BARS). One hundred thirty-four SCA patients were assessed: 17 SCA1, 13 SCA2, 55 SCA3, 2 SCA5, 22 SCA6, 11 SCA7, 9 SCA8, and 5 SCA17, mainly in the early stages of disease (67.2% stage 0-1). Oculomotor abnormalities were present on initial assessment in 94.8%, including 7/9 stage 0 and 77/81 stage 1 patients. Stage 0/1 patients had frequent saccadic intrusions, nystagmus, and hypo/hypermetric saccades. Saccadic slowing was present even in early stage SCA7 and SCA2, eventually leading to ophthalmoplegia. The burden of oculomotor abnormalities correlated with disease stage, duration, and severity, remaining highly significant even when controlling for age. The ubiquitous presence of oculomotor abnormalities in the SCAs, particularly early in the course, underscores the importance of oculomotor assessment in ataxia rating scales such as BARS. These findings highlight the potential for quantitative physiological oculomotor measures as clinical biomarkers in natural history studies and clinical trials.
Cerebellum 2019 Dec
PMID:Eye Movement Abnormalities Are Ubiquitous in the Spinocerebellar Ataxias. 3117 30