Familial Hyperinsulinism (KCNJ11-Related) (KCNJ11)
Familial hyperinsulinism (KCNJ11-related) is an autosomal recessive, pan-ethnic disorder caused by pathogenic variants in the gene KCNJ11. While age of onset and severity can vary between patients, affected infants usually have a high birth weight. The inadequate suppression of insulin secretion results in severe hypoglycemia causing seizures and coma. This hypoglycemia can be difficult to regulate with diet and medication and may require surgical resection of the pancreas. Without early diagnosis and treatment, hypoglycemia may result in brain damage. With proper treatment, life expectancy is normal. Some patients may have a milder phenotype, which can make diagnosis difficult. The severity of the disease cannot be predicted based on the inherited variants. In approximatley 1% of cases where only the father is a carrier of a KCNJ11 mutation, a somatic loss of the maternal allele during fetal development results in focal congenital hyperinsulinism. Typically, surgical removal of the focal lesion is curative.
For information about carrier frequency and residual risk, please see the residual risk table.