A team of twelve geneticists and neurologists from centers in the Netherlands studied the phenotypes and penetrance of paroxysmal kinesigenic dyskinesia (PKD), infantile convulsion and choreoathetosis (ICCA) syndrome, and benign familial infantile convulsions (BFIC), caused by PRRT2 mutations. Three different PRRT2 heterozygous mutations were detected in 2 families with ICCA, 2 families with PKD, and one individual with sporadic PKD. PRRT2 mutations were not detected with febrile convulsions or with migraine. The estimated penetrance of PRRT2 mutations in cases involving only PKD was 61%; it was nearly complete if infantile convulsions (BFIC) were also included. The identification of PRRT2 as a major gene for the PKD-ICCA-BFIC spectrum allows better disease classification, molecular confirmation of the clinical diagnosis, and genetic testing and counseling. [1]

COMMENT. PRRT2 mutations are the major cause of PKD or ICCA, but they are not involved in the etiology of febrile convulsions and migraine. Paroxysmal kinesigenic dyskinesia/choreoathetosis is characterized by brief attacks of involuntary movements (dystonia, chorea, athetosis, and ballism), precipitated by a kinesigenic trigger such as sudden movement or startle. Attacks last <1 minute, without loss of consciousness; they begin during childhood, and are controlled by anticonvulsant medication. Neurologic examination and MRI are normal, and ictal EEG shows nonspecific abnormalities. PKD is sporadic or familial. Familial cases have an autosomal dominant transmission with incomplete penetrance. PKD may be associated with BFIC or ICCA and with migraine.