Infections, recurrent, associated with encephalopathy, hepatic dysfunction and cardiovascular malformations
The FADD gene at 11q13.3 codes for the adapter peptide with 208 amino acids, FAS-associated death domain protein. This is a component of both the ripoptosome and death-inducing signaling complex (DISC), both important organelles in programmed cell death. It can be regarded as an apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated CD95 (FAS receptor, where its death domain binds to the corresponding domain within Fas receptor forming the DISC) or CD120a (tumour necrosis factor receptor 1A) receptors. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis and necroptosis. Involved in the interferon-mediated antiviral immune response, with a role in the positive regulation of interferon signalling.
Mutations of FADD cause infections, recurrent, associated with encephalopathy, hepatic dysfunction and cardiovascular malformations (IEHDCM, OMIM:613759) which is an autoimmune lymphoproliferative syndrome causing recurrent, episodes of fever, encephalopathy, and mild liver dysfunction sometimes accompanied by generalized seizures. Triggers include varicella zoster virus, MMR attenuated vaccine, parainfluenza virus, and Epstein-Barr virus.