The Genetics of Benign Paroxysmal Torticollis of Infancy: Is There an Association With Mutations in the CACNA1A Gene?

Benign paroxysmal torticollis of infancy is an unusual movement disorder, often accompanied by a family history of migraine. Some benign paroxysmal torticollis cases are associated with CACNA1A mutations. The authors sought to determine the frequency of CACNA1A mutations in benign paroxysmal torticollis by testing 8 children and their parents and by searching the literature for benign paroxysmal torticollis cases with accompanying CACNA1A mutations or other disorders linked to the same gene. In our 8 benign paroxysmal torticollis cases, the authors found 3 different polymorphisms, but no pathogenic mutations. By contrast, in the literature, the authors found 4 benign paroxysmal torticollis cases with CACNA1A mutations, 3 with accompanying family histories of 1 or more of familial hemiplegic migraine, episodic ataxia, and paroxysmal tonic upgaze. Thus, CACNA1A mutations are more likely to be found in children with benign paroxysmal torticollis if accompanied by family histories of familial hemiplegic migraine, episodic ataxia, or paroxysmal tonic upgaze.

Expression of c-FOS in the brain after activation of L-type calcium channels.

In rodents, administration of the L-type calcium channel activators, +/-Bay K 8644 and FPL 64176, causes an unusual neurobehavioral syndrome that includes dystonia and self-injurious biting. To determine the regional influence of these drugs in the brain, the induction of c-FOS was mapped after administration of these drugs to mice. In situ hybridization with an antisense riboprobe directed to c-FOS mRNA revealed widespread induction, with the highest levels in the striatum, cortex, hippocampus, locus coeruleus, and cerebellum. The induction of c-FOS mRNA was dose dependent, reached maximal expression approximately 60 min after drug treatment, and could be blocked by pretreatment with the L-type calcium channel antagonist, nifedipine. Immunohistochemical stains with an antibody directed to c-FOS protein revealed a pattern of induction similar to that obtained with in situ hybridization in most brain regions. These results demonstrate a very heterogeneous influence of L-type calcium channel activation in different brain regions, despite the nearly universal expression of these channels implied by more classical anatomical methods.