Familial dyskinesia and facial myokymia (FDFM): A novel movement disorder

We describe here familial dyskinesia and facial myokymia (FDFM), a novel au tosomal dominant disorder characterized by adventitious movements that some times appear choreiform and that are associated with perioral and periorbit al myokymia. We report a 5-generation family with 18 affected members (10 m ales and 8 females) with FDFM. The disorder has an early childhood or adole scent onset. The involuntary movements are paroxysmal at early ages, increa se in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improv ement in old age. The adventitious movements are worsened by anxiety but no t by voluntary movement, startle, caffeine, or alcohol. The disease is soci ally disabling, but there is no intellectual impairment or decrease in life span. A candidate gene and haplotype analysis was performed in 9 affected a nd 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to II regions containing genes associated with chorea and myokymia : 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dyston ic choreoathetosis gene at 2q34; 3) the dentatorubral-pallidoluysian atroph y gene at 12p13; 4) the choreoathetosis/spasticity disease locus on Ip that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chore a-acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11,2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and th e CACNA1A gene, a brain-specific P/Q-type calcium channel gene associated w ith ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition.