Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebellar hypoplasia is common to a variety of congenital disorders. Both stable conditions and progressive (degenerative) disorders may cause cerebellar hypoplasia. Pontocerebellar hypoplasia (PCH) is distinct from cerebellar hypoplasias in general, because the ventral pons is affected. Reviewing both clinical and neuropathological evidence, two specific neurogenetic entities are delineated. It is proposed to call these, respectively, type 1 (PCH-1) and type 2 (PCH-2). In type 1 the hallmark is the presence of spinal anterior horn degeneration similar to Werdnig-Hoffmann disease. Presentation in the neonatal period is characterized by respiratory insufficiency, frequent congenital contractures, and a combination of central and peripheral motor signs. Patients die early, usually before 1 year of age. In type 2 the hallmark is the presence of chorea/dystonia, which is often severe, while spinal anterior horn pathology is absent. Patients have microcephaly and severely impaired mental and motor development. They frequently die during childhood. Neuronal degeneration in both types of PCH is non-specific. Reactive changes in the degenerated parts appear more extensive in type 1. Examples of both types are given. Differentiation of the two types appears straightforward and possible by clinical means. Carbohydrate-deficient glycoprotein syndrome, one other cause of (ponto)cerebellar hypoplasia, should be excluded in all cases of PCH by appropriate means.
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PMID:Pontocerebellar hypoplasias. An overview of a group of inherited neurodegenerative disorders with fetal onset. 814 99

Pontocerebellar hypoplasia type 2 (PCH2) is a very rare autosomal recessive disorder. We report two unrelated female patients born to consanguineous parents presenting with this condition. Patient 1 showed a classical clinical/neuroradiological phenotype of PCH2 with dyskinesia/dystonia. Patient 2 had a neonatal onset of PCH2 with polyhydramnios, apneic spells, myoclonus, and an akinetic/rigidity condition. Neuroradiologically, patient 2 showed extensive pancerebral degeneration. Based on these observations, and in accordance with the published cases, two groups of PCH2 patients may be defined: (a) patients with dyskinesia/dystonia, severe hypoplasia of the infratentorial structures and less severe involvement of the supratentorial brain; and (b) patients with polyhydramnios, neonatal onset with tremulousness (hyperekplexia), no spontaneous activity, absence of dyskinesia and pancerebral degeneration. Finally, we report a dramatic positive response of the patient with dyskinesia/dystonia to levodopa treatment, and discuss the associated physiopathological implications.
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PMID:Pontocerebellar hypoplasia type 2: further clinical characterization and evidence of positive response of dyskinesia to levodopa. 1202 50

Pontocerebellar hypoplasia type 2, an autosomal recessive neurodegeneration with prenatal onset, is characterised by progressive microcephaly and chorea/dystonia and has not previously been associated with muscular involvement. The gene associated with PCH-2 is unknown. An episode of rhabdomyolysis is reported in two non-related children with PCH-2, fatal in one, precipitated by intercurrent disease. Muscle biopsies in two other PCH-2 patients, and in one rhabdomyolysis patient whose biopsy antedated this complication showed areas of myofibrillar disruption or necrosis. Postmortem muscle sampled in another case without neuromuscular symptoms revealed focal necrosis, regenerating small fibres and upregulation of HLA-ABC. Random serum creatine kinase values in six other PCH-2 patients without clinical signs of neuromuscular involvement were increased in four. Collected data provide preliminary evidence of a subclinical myopathy associated with PCH-2.
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PMID:Rhabdomyolysis in pontocerebellar hypoplasia type 2 (PCH-2). 1782 55

Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P < 0.0005) between TSEN54 mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared. Mutations in TSEN54 are clinically associated with dyskinesia and/or dystonia and variable degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms, ventilator dependency and early death. In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations.
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PMID:Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. 2160 47

Pontocerebellar hypoplasia type 6 (PCH6) (MIM #611523) is a recently described disorder caused by mutations in RARS2 (MIM *611524), the gene encoding mitochondrial arginyl-transfer RNA (tRNA) synthetase, a protein essential for translation of all mitochondrially synthesised proteins. This case confirms that progressive cerebellar and cerebral atrophy with microcephaly and complex epilepsy are characteristic features of PCH6. Additional features of PCH subtypes 2 and 4, including severe dystonia, optic atrophy and thinning of the corpus callosum, are demonstrated. Congenital lactic acidosis can be present, but respiratory chain dysfunction may be mild or absent, suggesting that disordered mitochondrial messenger RNA (mRNA) translation may not be the only mechanism of impairment or that a secondary mechanism exists to allow some translation. We report two novel mutations and expand the phenotypic spectrum of this likely underdiagnosed PCH variant, where recognition of the characteristic neuroradiological phenotype could potentially expedite genetic diagnosis and limit invasive investigations.
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PMID:Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2. 2208 4

Pontocerebellar hypoplasia type 2 is an autosomal recessive disorder characterized by hypoplasia and atrophy of the cerebellum and pons, leading to microcephaly, dystonia/dyskinesia, seizures, and severe cognitive impairment. Until lately it was considered a CNS-refined disease, but recent reports have associated it with muscular defects, as well. A 5-year-old boy with genetically confirmed pontocerebellar hypoplasia type 2 is described. The patient had all the clinical and radiological features of the disease, but he, additionally, exhibited two episodes of rhabdomyolysis precipitated by respiratory infections. The possible mechanisms associating encephalopathy and myopathy in pontocerebellar hypoplasia type 2 are discussed.
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PMID:Recurrent episodes of rhabdomyolysis in pontocerebellar hypoplasia type 2. 2317 18

Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of all genetically verified PCH1 cases. Homozygous p.G31A/EXOSC3 mutation was identified in 14 Roma patients, representing three fourths of all our SMN1-negative Roma SMA cases. The phenotype of the p.G31A/EXOSC3 homozygotes was compared to the clinical presentation of all reported to date genetically verified PCH1 cases. Signs of antenatal onset of disease present at birth were common in all PCH1 sub-types except in the homozygous p.D132A/EXOSC3 patients. The PCH1sub-types with early death (between ages 1 day and 17 months), seen in patients with p.G31A/EXOSC3 or SLC25A46 mutations have a SMA type 1-like clinical presentation but with global developmental delay, visual and hearing impairment, with or without microcephaly, nystagmus and optic atrophy. Mutations with milder presentation (homozygous p.D132A/EXOSC3 or VRK1) may display additionally signs of upper motor neuron impairment, dystonia or ataxia and die at age between 5 and 18 years. Other EXOSC3 mutations and EXOSC8 cases are intermediate - SMA type 1-like presentation, spasticity (mostly in EXOSC8) and death between 3 months and 5 years. There is no correlation between neurological onset and duration of life. We add marble-like skin and congenital laryngeal stridor as features of PCH1. We show that imaging signs of cerebellar and pontine hypoplasia may be missing early in infancy. EMG signs of anterior horn neuronopathy may be missing in PCH1 patients with SLC25A46 mutations. Thus, there is considerable phenotypic variability in PCH1, with some cases being more SMA-like, than PCH-like. Detailed clinical evaluation and ethnicity background may guide genetic testing and subsequent genetic counseling.
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PMID:Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature. 2965 27