Abstracts

To describe familial paroxysmal choreoathetosis associated with epileptiform abnormalities in a large family of French and Chippewa Native Americans. Epilepsy and epileptiform abnormalities have been described in familial kinesiogenic dyskinesias and choreoathetosis. To our knowledge, no cases of familial non-kinesiogenic paroxysmal choreoathetosis associated with epileptiform abnormalities have been reported.
A 34-year-old right handed woman and two of her four sons, ages 8 and 10, presented with spells of [quot]jumpy legs.[quot] In all individuals, the spells started at 3 years of age and were characterized by choreoathetoid movements of legs greater than arms, lasting 30 minutes up to 2 hours with preservation of awareness. Spells are limited to wakefulness. The mother[apos]s EEGs had consistently shown interictal generalized 3 Hz spike-and-wave discharges without temporal relationship to the clinical events. She does have a history of migraine headaches which at times occur during spells. Phenytoin, lamotrigine, and valproic acid were tried in the mother but were ineffective; oxcarbazepine was effective in decreasing spell frequency, duration, and intensity. Brain MRI in the mother was normal. In the mother and her affected sons, copper, ceruloplasmin levels, iron studies, and thyroid function tests were normal. There is some variability of the presentation within family members; the 8-year-old son has daily or every-other-day spells not improved on phenytoin monotherapy, while the 10-year-old son has spells about once per month and is not on medication. Both children also have headaches. There is no known history of epileptic seizures or cognitive decline. The family history is remarkable for multiple family members (approximately 22) with the same syndrome. Only one family member (mother[apos]s brother) had any evidence of seizures-- he had a single generalized tonic-clonic seizure. A pedigree of affected and unaffected relatives was constructed and blood was drawn for DNA analysis.
The inheritance pattern appears to be autosomal dominant with incomplete penetrance. Several family members have had EEGs, many of which have shown epileptiform abnormalities. Four major voltage-gated sodium channels of the central and peripheral nervous system, SCN1A, SCN2A, SCN3A on chromosome 2q24 and SCN8A on chromosome 12q13 are being evaluated as candidate genes by screening for coding and splice site mutations.
Prior studies have established that epilepsy and paroxysmal movement disorders may occur together in a familial pattern, and ion channel dysfunction may be the basis of this association. Our patients and their affected family members may represent a variant of this phenomenon.