In approximately 20 % of patients with OPA1 mutations, a more complex neurodegenerative disorder with extraocular manifestations, known as ADOA Plus, can arise.
Specific OPA1 mutations are responsible for several distinct clinical presentations, such as ADOA with deafness (ADOAD), and severe multi-systemic syndromes, the so-called "ADOA plus" disorders, which involve neurological and neuromuscular symptoms similar to those due to mitochondrial oxidative phosphorylation defects or mitochondrial DNA instability.