Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe patients from five generations of a pedigree with mutations in the spinocerebellar ataxia type 2 gene (SCA2). The predominant clinical features observed included both appendicular and truncal ataxia, dysarthria, slowness of saccades, and impaired optokinetic responses. Successive generations demonstrated both earlier ages of onset as well as increasing numbers of trinucleotide repeat sequences. The signs found in this family are compared with the description of other families with SCA2 as well as with other types of dominantly inherited spinocerebellar ataxias.
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PMID:Clinical and molecular analysis of a pedigree of southern Italian ancestry with spinocerebellar ataxia type 2. 933 11

Using a molecular diagnostic approach, we investigated 101 kindreds with autosomal dominant cerebellar ataxias (ADCAs) from the central Honshu island of Japan, including spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2), Machado-Joseph disease (MJD), dentatorubral and pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 6 (SCA6). In our unselected series, MJD was the most common type of ADCA, accounting for 33.7% followed by DRPLA (19.8%), SCA2 (5.9%) and SCA6 (5.9%). No SCA1 mutations were identified. We analysed the clinical features of six molecular confirmed SCA6 kindreds: in each family, there was an expanded allele in the alpha1A-voltage dependent calcium channel comprising between 23 and 25 CAG repeats. The mean age at onset of symptoms was 43+/-13 years. The clinical features consisted predominantly of cerebellar ataxia, dysarthria and horizontal nystagmus, which was generally consistent with ADCA type 3. However several new clinical features were found in some patients: dramatic anticipation, rapid disease progression, severe ataxia associated with action tremor or action myoclonus, and very early onset, which are not described as the classical features of ADCA type 3.
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PMID:Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6. 955 Mar 56

We report on 2 brothers, Patients 1 and 2, who presented with a similar clinical syndrome consisting of resting tumor, bradykinesia, rigidity, and dysarthria at the ages of 40 and 43 years, respectively. An excellent response to levodopa therapy was observed throughout the disease course. No gait or limb ataxia, slow saccades, or decreased tendon reflexes were detected, but unsteadiness of gait with propulsion developed recently in Patient 1 approximately 25 years after disease onset. Magnetic resonance imaging demonstrated mild atrophy of the pons and cerebellum in Patient 1 and cerebellar atrophy in Patient 2. Expanded CAG repeats, numbering 36, in one allele of the ataxin-2 gene were identified in Patient 1 only; his brother was not available for this investigation. With [(99m)Tc]TRODAT-1 single photon emission computed tomography of the brain, a significant bilateral and asymmetrical reduction of striatal dopamine transporters was found in Patient 1 compared to healthy controls. This bilateral reduction of striatal dopamine transporters resembled that observed in a set of controls with Parkinson's disease who had asymmetrical impairment. These results suggest that patients with familial parkinsonism who present with typical Parkinson's disease should be screened for the genetic defect of spinocerebellar ataxia type 2. The presynaptic impairment of nigrostriatal function is very likely to be the reason for levodopa responsiveness.
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PMID:Dopa-responsive parkinsonism phenotype of spinocerebellar ataxia type 2. 1236 May 57

We herein report a case of a 45-year-old man who was diagnosed with spinocerebellar ataxia type 2 (SCA 2) by genomic testing and whose grandmother, father, and uncle were also affected by the same disease. The patient had noted difficulty in walking and dysarthria since the age of 43. Neurological examination revealed lid retraction with prominent eyes, cerebellar ataxia and pyramidal signs including spasticity, ankle clonus, and hyperreflexia with pathological reflexes. MRI showed atrophy of the cerebellum, brain stem, and spinal cord. This case report suggests that the lid retraction with prominent eyes and pyramidal signs are sometimes major features in SCA2.
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PMID:[A case of spinocerebellar ataxia type 2 presenting with lid retraction with prominent eyes and pyramidal signs]. 1282 May 59

In spite of the considerable progress in clinical and molecular research, knowledge regarding brain damage in spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) still is limited and the extent to which the thalamus is involved in both diseases is uncertain. Accordingly, we performed a pathoanatomical analysis on serial thick sections stained for lipofuscin granules and Nissl substance through the thalami of two genetically confirmed cases: one an SCA2 patient, the other an SCA3 patient. During this systematic study, we detected severe destruction of the reticular (RT), fasciculosus (FA), ventral anterior (VA), ventral lateral (VL), ventral posterior lateral (VPL), ventral posterior medial (VPM), cucullar (CU) and mediodorsal thalamic nuclei (MD), the lateral geniculate body (LGB) and inferior nucleus of the pulvinar (PU i) in the SCA2 case, and a severe neuronal loss in the RT, FA, VA and PU i of the SCA3 case. In the SCA2 patient, additional obvious neuronal loss was observed in all nuclei of the anterior and rostral intra laminar groups, in the lateral posterior nucleus (LP), the lateral (PU l) and the medial subnuclei of the pulvinar (PU m), whereas in the SCA3 patient only two of the nuclei that belong to the anterior thalamic group, the VL, VPL, VPM, LP, LGB, PU l and PU m, displayed marked neurodegeneration. These novel findings indicate that thalamic involvement in SCA2 and SCA3 patients has been underestimated in the past. In view of what is known about the functions of the affected thalamic nuclei, the present findings provide an appropriate pathoanatomical explanation for some of the disease-related symptoms seen in both of our and other SCA2 and SCA3 patients: gait, stance, truncal and limb ataxia, dysarthria or anarthria, falls, dysdiadochokinesia and bradykinesia, problems with writing, somatosensory deficits, saccadic dysfunctions, executive dysfunctions and abnormalities of visual evoked potentials.
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PMID:Thalamic involvement in a spinocerebellar ataxia type 2 (SCA2) and a spinocerebellar ataxia type 3 (SCA3) patient, and its clinical relevance. 1284 80

An 11-year-old boy was evaluated for progressive ataxia, cognitive deterioration, and ophthalmoplegia. The child initially presented with abnormal eye movements at the age of 2 months and was noted to have developmental delay at 6 months. At the age of 7 years, he developed ataxia and cognitive impairment, and subsequently manifested dysphagia and incontinence. The pertinent family history included gait difficulty in the paternal grandmother. At the age of 11, his general physical examination was normal. On neurological examination, he had bilateral external ophthalmoplegia, ataxic dysarthria, dysmetria and tremor in the upper extremities, and marked gait ataxia. An ophthalmological evaluation showed no evidence of pigmentary retinopathy. Brain MRI demonstrated cerebellar, brainstem, and cerebral atrophy. An ataxia panel showed 62 repeats in one allele of the SCA2 gene. Most cases of spinocerebellar ataxia type 2 (SCA2) present between 20 years and 40 years, and affected individuals typically have between 34 and 57 CAG repeats. Neonatal cases of SCA2 have been reported in individuals with over 200 CAG repeats. Childhood SCA2 has been reported previously in two patients but not described clinically. This case broadens the spectrum of the clinical features of infantile-onset SCA2 and highlights the importance of considering this diagnosis in infants and children.
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PMID:Spinocerebellar ataxia type 2 (SCA2) presenting with ophthalmoplegia and developmental delay in infancy. 1473 88

Spinocerebellar ataxia type 2 (SCA2) is caused by a CAG trinucleotide repeat expansion within the coding region of the ataxin-2 gene. Affected individuals typically have between 34 and 57 CAG repeats. Signs of the disorder generally begin in adulthood and include progressive ataxia, dysarthria, tremor, hyporeflexia, and slow saccades. As with other trinucleotide repeat disorders, SCA2 exhibits an inverse correlation between the size of the CAG repeat and the age at onset of clinically detectable disease, with neonatal cases of SCA2 being reported in individuals harboring over 200 CAG repeats. However, a wide range of age at onset is typically observed, especially in individuals with < 40 CAG repeats. CAG repeat number alone explains approximately 25-80% of the variability. In this paper, we hypothesize that the level of mutant ataxin-2 protein in affected cells contributes to these differences. One of the mechanisms that might influence this protein levels is de novo DNA methylation, which would specifically target the allele with the expanded CAG repeat leading to transcriptional silencing. Consequently, the symptoms of SCA2 would occur later in the patient's life history. Our postulations, as well as those previously reported to account for the phenotype of SCA2, are discussed.
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PMID:Can ataxin-2 be down-regulated by allele-specific de novo DNA methylation in SCA2 patients? 1550 70

The pre-cerebellar nuclei act as a gate for the entire neocortical, brainstem and spinal cord afferent input destined for the cerebellum. Since no pathoanatomical studies of these nuclei had yet been performed in spinocerebellar ataxia type 2 (SCA2) or type 3 (SCA3), we carried out a detailed postmortem study of the pre-cerebellar nuclei in six SCA2 and seven SCA3 patients in order to further characterize the extent of brainstem degeneration in these ataxic disorders. By means of unconventionally thick serial sections through the brainstem stained for lipofuscin pigment and Nissl material, we could show that all of the pre-cerebellar nuclei (red, pontine, arcuate, prepositus hypoglossal, superior vestibular, lateral vestibular, medial vestibular, interstitial vestibular, spinal vestibular, vermiform, lateral reticular, external cuneate, subventricular, paramedian reticular, intercalate, interfascicular hypoglossal, and conterminal nuclei, pontobulbar body, reticulotegmental nucleus of the pons, inferior olive, and nucleus of Roller) are among the targets of both of the degenerative processes underlying SCA2 and SCA3. These novel findings are in contrast to the current neuropathological literature, which assumes that only a subset of pre-cerebellar nuclei in SCA2 and SCA3 may undergo neurodegeneration. Widespread damage to the pre-cerebellar nuclei separates all three phylogenetically and functionally defined regions of the cerebellum, impairs their physiological functions and thus explains the occurrence of gait, stance, limb and truncal ataxia, dysarthria, truncal and postural instability with disequilibrium, impairments of the vestibulo-ocular reaction and optokinetic nystagmus, slowed and saccadic smooth pursuits, dysmetrical horizontal saccades, and gaze-evoked nystagmus during SCA2 and SCA3.
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PMID:Spinocerebellar ataxias types 2 and 3: degeneration of the pre-cerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum. 1578 63

Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine nuclei, inferior olives, and Purkinje cell degeneration. This form of autosomal dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria. Although the motor dysfunction is well characterized in these patients, nothing is known about their motor learning capabilities. Here we tested 43 SCA2 patients and their matched controls in prism adaptation, a kind of visuomotor learning task. Our results show that their pattern of brain damage does not entirely disrupt motor learning. Rather, patients had impaired adaptation decrement, but surprisingly a normal aftereffect. Moreover, the mutation degree could discriminate the degree of adaptation. This pattern could reflect the net contribution of two adaptive mechanisms: strategic control and spatial realignment. Accordingly, SCA2 patients show an impaired strategic control that affects the adaptation rate, but a normal spatial realignment measured through the aftereffect. Our results suggest that the neural areas subserving spatial realignment are spared in this form of spinocerebellar ataxia.
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PMID:Prism adaptation in spinocerebellar ataxia type 2. 1750 59

Autosomal dominant spinocerebellar ataxias are neurodegenerative disorders that generally present in adulthood. Due to extreme expansion of the repeat size during spermatogenesis, they can also be observed in childhood. The diagnosis in childhood is very difficult in the absence of family history. Here we describe an 8-year-old girl with spinocerebellar ataxia type 2 who presented with progressive ataxia, cognitive deficits, and dysarthria. A detailed family history exhibited similarly affected cases on the paternal side. Molecular testing for spinocerebellar ataxia type 2 revealed abnormal "cytosineadenine-guanosine" expansion in all affected family members. The number of cytosine-adenine-guanosine repeats in the index case was 70. The mean size of expansion in the relatives of the patient was 42 (39-46). This finding explains the early onset of symptoms in the index case.
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PMID:Spinocerebellar ataxia type 2 in a Turkish family. 1771 86


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