Evaluation of candidate loci culminated in the identification of a heterozygous 
missense mutation (R67W) in KCNJ2, the gene encoding the inward-rectifying 
potassium current, Kir2.1, in 41 members of a kindred in which ventricular 
arrhythmias (13 of 16 female members [81%]) and periodic paralysis (10 of 25 
male members [40%]) segregated as autosomal dominant traits with sex-specific 
variable expressivity. Some mutation carriers exhibited dysmorphic features, 
including hypertelorism, small mandible, syndactyly, clinodactyly, cleft palate, 
and scoliosis, which, together with cardiodysrhythmic periodic paralysis, have 
been termed "Andersen syndrome." However, no individual exhibited all 
manifestations of Andersen syndrome, and this diagnosis was not considered in 
the proband until other family members were examined. Other features seen in 
this kindred included unilateral dysplastic kidney and cardiovascular 
malformation (i.e., bicuspid aortic valve, bicuspid aortic valve with 
coarctation of the aorta, or valvular pulmonary stenosis), which have not been 
previously associated. Nonspecific electrocardiographic abnormalities were 
identified in some individuals, but none had a prolonged QT interval. 
Biophysical characterization of R67W demonstrated loss of function and a 
dominant-negative effect on Kir2.1 current. These findings support the 
suggestion that, in addition to its recognized role in function of cardiac and 
skeletal muscle, KCNJ2 plays an important role in developmental signaling.