Sir, The current report by Carelli and colleagues is a timely contribution the literature on autosomal dominant optic atrophy (DOA) (Carelli et al. , 2014). Similar to a recently published Letter to the Editor in Brain by Bonneau et al. (2014), they describe the intriguing association of a Behr-like phenotype in an Italian family harbouring presumed compound heterozygous OPA1 mutations. The majority of patients with DOA harbour single heterozygous mutations within the OPA1 gene and haploinsufficiency is widely regarded as the major disease mechanism that precipitates retinal ganglion cell loss and progressive visual failure (Lenaers et al. , 2012). However, several fundamental questions remain unanswered, in particular, the wide intra- and inter-familial variability in disease severity that is observed not only in relation to the degree of visual loss, but also with the increasing realisation that a sizeable proportion of OPA1 mutation carriers will develop significant neurological complications during their lifetime (Yu-Wai-Man et al. , 2010). We must now reconcile these diverging genotypes and phenotypes in a disorder that has until recently been viewed as being limited to the optic nerve with a straightforward …