title: Acute optic neuropathy associated with a novel MFN2 mutation.
abstract: Mutations in the mitofusin 2 (MFN2) gene cause CMT2A the most common form of autosomal dominant axonal Charcot-Marie-Tooth (CMT). In addition, mutations in MFN2 have been shown to be responsible for Hereditary Motor Sensory Neuropathy type VI (HSMN VI), a rare early-onset axonal CMT associated with optic neuropathy. Most reports of HMSN VI presented with a sub-acute form of optic neuropathy. Herein, we report a CMT2A patient, who developed very rapidly progressing severe optic neuropathy. A 40-year-old Caucasian man was evaluated for gait disturbance and lower limbs weakness, slowly progressed over the last 2 years. Due to clinical data and family history, a diagnosis of CMT2 was made. The novel heterozygous c.775C > T (p.Arg259Cys) mutation in MFN2 was detected in the patient and his clinical affected mother. Interestingly, the patient developed a severe sudden bilateral visual deterioration few years early, with clinical and instrumental picture suggestive of acute bilateral optic neuropathy. Our report expands the spectrum of MFN2-related manifestation because it indicates that visual symptoms of HMSN VI may enter in the differential with acquired or hereditary acute optic neuropathies, and that severe optic neuropathy is not invariably an early manifestation of the disease but may occur as disease progressed. This report could have an impact on clinicians who evaluate patients with otherwise unexplainable bilateral acute-onset optic neuropathy, especially if associated with a motor and sensory axonal neuropathy.
authors.affiliation: Dept. Scienze e Biotecnologie Medico-Chirurgiche, Rome Sapienza University Polo Pontino, Rome, Italy, leonardi.luca89@gmail.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Leonardi
authors.forename: Christian
authors.initials: C
authors.lastname: Marcotulli
authors.forename: Eugenia
authors.initials: E
authors.lastname: Storti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Mariano
authors.initials: M
authors.lastname: Serrao
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Parisi
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Pierelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Casali
mesh_terms: D000328:Adult; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009901:Optic Nerve Diseases / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human