Congenital Hyperinsulinism and Long QT Syndrome Attributable to a Variant in KCNE1

This is a report of a child with congenital hyperinsulinism associated with a loss-of-function variant in KCNE1. KCNE1 encodes a human potassium channel accessory (beta) subunit that modulates potassium channel Kv7.1 (encoded by KCNQ1). Loss-of-function pathogenic variants in either the KCNQ1 or KCNE1 genes result in long QT syndrome by causing prolongation in the action potential duration at the cellular level. In addition to long QT syndrome, the phenotype associated with loss-of-function pathogenic variants in KCNQ1 is characterized by postprandial hyperinsulinemic hypoglycemia.

Clinical data for the proband were extracted from the medical records. The proband presented with fasting hypoglycemia due to hyperinsulinism in early childhood as well as postprandial hypoglycemia triggered by carbohydrates and by protein. Whole-exome sequencing was undertaken in genomic DNA isolated from proband and both parents. Whole-exome sequencing revealed a variant in KCNE1 inherited from the father, who also has a history of hyperinsulinism. Both the patient and father were subsequently diagnosed with long QT syndrome. The proband and father underwent phenotype testing including fasting test, oral glucose tolerance test, oral protein tolerance test, and exercise tolerance test.

This case illustrates that loss-of-function variants in KCNE1, similar to KCNQ1, are associated with a cardiac and a beta cell phenotype, and thus, this patient population should be screened for hypoglycemia, particularly in the postprandial state.