At present, there is insufficient evidence to confirm a causal relationship between CACNA1C and congenital hyperinsulinism. While CACNA1C is an established disease gene for Timothy syndrome and Brugada syndrome, its role in isolated hyperinsulinism remains unclear. Although approximately 40% of individuals with Timothy syndrome report episodes of hypoglycaemia, increased insulin secretion or action has not been confirmed as the underlying mechanism in these patients.
Only limited case-level evidence exists linking CACNA1C variants to hyperinsulinism, without consistent segregation data or convincing mechanistic support. Given the large size and high polymorphism of calcium channel genes, rare missense variants may be identified incidentally and should be interpreted with caution. We are currently screening CACNA1C in patients with hyperinsulinism to gain further insight into its potential role in this condition.