A Complex Phenotype in an Adult with Recurrent Syncope (P8-5.020)

A 70 year male who has a Complex phenotype with at chronic history of persistent autonomic dysfunction compatible with pure autonomic failure. He subsequently revealed to have chronic hyposmia and REM sleep behaviour which was followed by subsequent development of clinical Parkinsonism and abnormal DAT. He was noted with bilateral nonfatigable ptosis and early external ophthalmoplegia and reported a insidious onset of gradually reduced visual acuity and abnormal/delayed visual evoked responses bilaterally suggestive of optic neuropathy. During his follow up he was diagnosed with a left PCA territory infarct. Due to the multidomain neurological symptomatology and after extensive investigations, mitochondrial genetic testing has identified a pathogenic mutation in TWNK confirming a diagnosis of autosomal dominant TWNK-related mitochondrial disease. The natural history of TWNK related mitochondrial disorders is that it is invariably fatal and most commonly present during childhood as a life shortening and terminal illness.