A syndrome of congenital hyperinsulinism and rhabdomyolysis is caused by KCNJ11 mutation.

Background Congenital hyperinsulinism is a genetically heterogeneous disorder, but mutations in the components of the ATP-sensitive potassium channel K-(ATP) account for more than a third of all isolated congenital hyperinsulinism cases. The association between congenital hyperinsulinism and rhabdomyolysis has not been reported. Objective To describe significant skeletal muscle manifestations in a family with a novel mutation in KCNJ11 (encoding the Kir6.2 component of K-(ATP)). Methods Cross-sectional analysis of members of a large multiplex consanguineous family with congenital hyperinsulinism and rhabdomyolysis using autozygosity mapping and exome sequencing. Results Five affected members of an extended consanguineous Saudi family were recruited along with relevant unaffected relatives. We were able to map an apparently novel syndrome of congenital hyperinsulinism and severe rhabdomyolysis leading to acute renal failure to a single locus that harbours KCNJ11 in which we identified a novel homozygous mutation. Conclusions This study expands the phenotype associated with KCNJ11 loss of function in humans and calls for increased awareness of rhabdomyolysis as a potential late-onset life-threatening complication of KCNJ11-related congenital hyperinsulinism.