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)

We describe a pedigree in which 3 members in the same generation are affected by Rolandic epilepsy (RE), paroxysmal exercise-induced dystonia (PED), and writer's cramp (WC). Both the seizures and paroxysmal dystonia had a strong age-related expression that peaked during childhood, whereas the WC, also appearing in childhood, has been stable since diagnosis. Genome-wide linkage analysis performed under the assumption of recessive inheritance identified a common homozygous haplotype in a critical region spanning 6 cM between markers D16S3133 and D16S3131 on chromosome 16, cosegregating with the affected phenotype and producing a multipoint LOD score value of 3.68. Although its features are unique, this syndrome presents striking analogies with the autosomal dominant infantile convulsions and paroxysmal coreoathetosis (ICCA) syndrome, linked to a 10 cM region between D16S401 and D16S517, which entirely includes the 6 cM of the RE-PED-WC critical region. The same gene may be responsible for both RE-PED-WC and ICCA, with specific mutations explaining each of these Mendelian disorders. This report shows that idiopathic focal disorders such as epilepsy and dystonia, can be caused by the same genetic abnormality, may have a transient expression, and may be inherited as an autosomal recessive trait.
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PMID:Autosomal recessive rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp: delineation of the syndrome and gene mapping to chromosome 16p12-11.2. 1007 49

Although some motor manifestations of epilepsy and of paroxysmal dyskinesia may be difficult to differentiate clinically, the current understanding is that the two disorders are clinically distinct. However, there are several recent reports of families in which different individuals had either disorder or both manifestations, with age-related expression. Co-occurrence makes it likely that a common, genetically determined, pathophysiologic abnormality is variably expressed in the cerebral cortex and in basal ganglia. A rather homogeneous syndrome of autosomal dominant infantile convulsions and paroxysmal (dystonic) choreoathetosis (ICCA) was described in six families from France, China and Japan. Linkage analysis in the French and Chinese families allowed the mapping of the disease gene in a 10-cM interval within the pericentromeric region of chromosome 16. An Italian pedigree in which three members in the same generation were affected by rolandic epilepsy, paroxysmal exercise-induced dystonia (PED), and writer's cramp was subsequently reported. Linkage analysis showed a common homozygous haplotype in a critical region spanning 6 cM and entirely included within the ICCA critical region. Clinical analogies and linkage findings suggest that the same gene could be responsible for rolandic epilepsy, PED, writer's cramp (WC), and ICCA, with specific mutations accounting for each of these mendelian disorders. Evidence for a major gene or a cluster of genes for epilepsy and paroxysmal dyskinesia to the pericentromeric region of chromosome 16 is reinforced by the recent linkage of a family with autosomal dominant paroxysmal dyskinesia to a critical region partially overlapping with ICCA and contiguous to the RE-PED-WC regions. Additional autosomal dominant pedigrees are on record, from Australia and Italy, in which epilepsy was variably associated with paroxysmal kinesigenic or exercise-induced dystonia. Ion channel genes are potentially interesting candidates for syndromes featuring both these paroxysmal neurologic disorders. Increased awareness of their possible co-occurrence will certainly increase the number of observations in the next few years.
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PMID:Idiopathic epilepsy and paroxysmal dyskinesia. 1152 Mar 21