Mutations of the RET-GDNF signaling pathway in Ondine's curse

Sarcoidosis is a multi-systemic granulomatous disease of unknown cause. It commonly involves lymph nodes, lungs, eyes, and skin. Cardiac sarcoid may be isolated, or associated with systemic involvement. Cardiac involvement is found in 20-50% of autopsied patients with sarcoidosis. However, it only gives rise to clinical manifestations in about 5% of patients. Cardiac involvement by sarcoid has been reported to manifest as complete heart block, papillary muscle dysfunction, congestive heart failure, pericarditis and/or effusion, conduction abnormality or arrhythmia, chest pain, and sudden death. The most common site of involvement is the interventricular septum base, which when involved may lead to heart block or arrhythmia. We report a case of sudden death in a 33-year-old male with a history of surgically repaired congenital heart disease. Although his congenital heart disease was originally postulated to be important in his death, autopsy examination revealed cardiac sarcoid with prominent involvement of the conduction system.