Spastic paraplegia in 'dominant optic atrophy plus' phenotype due to OPA1 mutation

Abstract

Sir, We read the papers by Yu-Wai-Man et al. (2010) and Marelli et al. (2011) with much interest. The authors described three families with dominant optic atrophy plus phenotype due to OPA1 mutations presenting spastic paraplegia among the extra-ocular neurological features. Two families, reported by Yu-Wai-Man et al . (2010), harboured a deletion c.876-878del(TGT) and a nonsense GTPase mutation c.899C>T, respectively, both resulting in premature termination codons. The affected members presented neuropathy in addition to spastic paraplegia and dominant optic atrophy. Marelli et al. (2011) described a third family in which a missense mutation c.1652G>A in the dynamin domain was associated with Behr syndrome. We report here, a patient in whom a deletion c.2708_2711delTTAG of OPA1 was associated with dominant optic atrophy, spastic paraplegia, Duane retraction syndrome, migraine with atypical aura, patent foramen ovale and muscle fibre abnormalities. Considering the previous reports, we extend the mutations of OPA1 as possibly responsible for dominant optic atrophy plus phenotypes presenting spastic paraplegia, and identify some features shared by patients with optic atrophy plus and spastic pyramidal involvement. The proband, a 28-year-old Italian female belonging to a family from Sicily, has suffered from loss of central vision due to optic atrophy since childhood. She was referred to our unit for the onset, appeared a few years earlier, of slowly progressive …