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Paroxysmal kinesigenic dyskinesia and infantile convulsions: clinical and linkage studies
K J Swoboda1, B Soong, C McKenna
1Department of Neurology, Human Genetics, Howard Hughes Medical Institute, Salt Lake City, UT, USA. Swoboda@howard.genetics.utah.edu
Insights
This study clinically characterized paroxysmal kinesigenic dyskinesia (PKD) and found infantile convulsions are common in affected families. Linkage analysis confirmed a chromosome 16 locus, but locus heterogeneity was also observed.
Area of Science:
- Genetics
- Neurology
- Clinical Medicine
Background:
- Paroxysmal kinesigenic dyskinesia (PKD) involves recurrent involuntary movements triggered by sudden actions.
- An autosomal dominant PKD locus on chromosome 16 has been previously identified.
Purpose of the Study:
- To clinically characterize individuals with PKD across diverse ethnic backgrounds.
- To investigate the association between PKD and infantile convulsions.
- To confirm genetic linkage to a pericentromeric chromosome 16 locus.
Main Methods:
- Clinical characterization and interviews of 95 individuals from 11 families with PKD.
- Linkage analysis using markers across the chromosome 16 locus.
- Haplotype analysis to assess shared genetic regions in affected individuals.
Main Results:
- 44 out of 95 individuals exhibited paroxysmal dyskinesia, infantile convulsions, or both.
- Infantile convulsions were present in 9 of 11 families, with later seizures in only two individuals.
- A 26-cM linkage region on chromosome 16 was defined, but locus heterogeneity was suggested by a lack of shared haplotype in one family.
Conclusions:
- Understanding the PKD/infantile convulsions gene offers insights into disorders bridging epilepsy and movement disorders.
- Clinical characterization highlights the significant comorbidity of infantile convulsions with PKD.
Objective:
To clinically characterize affected individuals in families with paroxysmal kinesigenic dyskinesia (PKD), examine the association with infantile convulsions, and confirm linkage to a pericentromeric chromosome 16 locus.
Background:
PKD is characterized by frequent, recurrent attacks of involuntary movement or posturing in response to sudden movement, stress, or excitement. Recently, an autosomal dominant PKD locus on chromosome 16 was identified.
Methods:
The authors studied 11 previously unreported families of diverse ethnic background with PKD with or without infantile convulsions and performed linkage analysis with markers spanning the chromosome 16 locus. Detailed clinical questionnaires and interviews were conducted with affected and unaffected family members.
Results:
Clinical characterization and sampling of 95 individuals in 11 families revealed 44 individuals with paroxysmal dyskinesia, infantile convulsions, or both. Infantile convulsions were surprisingly common, occurring in 9 of 11 families. In only two individuals did generalized seizures occur in later childhood or adulthood. The authors defined a 26-cM region using linkage data in 11 families (maximum lod score 6.63 at theta = 0). Affected individuals in one family showed no evidence for a shared haplotype in this region, implying locus heterogeneity.
Conclusions:
Identification and characterization of the PKD/infantile convulsions gene will provide new insight into the pathophysiology of this disorder, which spans the phenotypic spectrum between epilepsy and movement disorder.