Paroxysmal Kinesigenic Choreoathetosis Locus Maps to Chromosome 16p11.2-q12.1

Abstract

Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To localize the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC. Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination fraction [theta] =.00; penetrance [p] =.7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 (p = 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of approximately 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile convulsions and paroxysmal choreoathetosis" (MIM 602066), a recently recognized clinical entity with benign infantile convulsions and nonkinesigenic paroxysmal dyskinesias.

The genetics of the dystonias – a review based on the new classification of the dystonias

“…Unlike PNKD-1, caffeine rarely triggers attacks and alcohol never does. Episodes, which are usually unilateral, are short-lasting (seconds to minutes) and more frequent than those observed in PNKDs, occurring over 100 times a day 59 .…”

“…Attacks normally start between six and sixteen years and are brought on by sudden, unexpected movements, hence the term kinesigenic. Men are more affected than women (ratio of men to women = 3.75:1) 59 . The locus responsible for PKD-1 has been mapped to the pericentromeric region of chromosome 16, 16p11.2-q12.1 59 .…”

“…Men are more affected than women (ratio of men to women = 3.75:1) 59 . The locus responsible for PKD-1 has been mapped to the pericentromeric region of chromosome 16, 16p11.2-q12.1 59 . The condition may present with different hyperkinesias (dystonia, chorea, athetosis or ballism) in 33% of cases, but dystonic movements on their own are most commonly reported (57%).…”

Benign familial infantile convulsions: a clinical study of seven Dutch families

“…induced by sudden voluntary movements. [12][13][14][15] Many patients report variable sensations preceding an attack. The dyskinesias usually last a few seconds, during which consciousness is preserved, and are easily controlled by AEDs.…”

“…ICCA has been mapped to chromosome 16p12-q12, the same region as has been identified in the above-mentioned French and Argentinian families with BFIC. [12][13][14][15] The responsible gene that is located in this area might, apparently, cause both BFIC with and without paroxysmal kinesigenic dyskinesias.…”