SHORT COMMUNICATION Atypical, perhaps under-recognized? An unusual phenotype of Friedreich ataxia Beate Diehl & Michael S. Lee & Janet R. Reid & Craig D. Nielsen & Marvin R. Natowicz Received: 3 August 2009 / Accepted: 29 December 2009 / Published online: 17 February 2010 # Springer-Verlag 2010 Abstract Friedreich ataxia (FRDA) is typically characterized by slowly progressive ataxia, depressed tendon reflexes, dysarthria, pyramidal signs, and loss of position and vibration sense with onset before 25 years. While several atypical forms of FRDA are recognized, profound vision deficit is rare. We describe here a 41-year-old man with profound vision deficit and episodic complete blindness associated with marked optic atrophy, spastic paraparesis, and sensory neuropathy without ataxia whose diagnostic evaluation revealed compound heterozygosity for two frataxin mutations, a 994 GAA repeat intronic expansion and c.389G>T (p.G130V) missense mutation. This case emphasizes that FRDA should be considered for individuals with significant vision deficit with optic atrophy and sensory neuropathy, even in the absence of ataxia. This case also raises the additional, related concern that prior studies may underestimate the frequency and varieties of variant forms of FRDA. Keywords Atypical Friedreich ataxia . Variant Friedreich ataxia . Frataxin . Mitochondrial . Optic atrophy Introduction Friedreich ataxia (FRDA), an autosomal recessive progressive neurological condition, is the most common inherited ataxia. Its onset is often in childhood and usually before 25 years of age. Clumsiness of gait and frequent falls is the most common initial presentation. Its subsequent course is typically that of a slowly progressive mixed cerebellar-sensory ataxia associated with dysarthria, muscle weakness, spasticity, scoliosis, blad- der dysfunction, loss of lower limb reflexes, and loss of propioception and vibration sensation. Cardiomyopathy and diabetes are other common, age-dependent findings [1]. Mutations in the frataxin (FXN) gene cause FRDA and approximately 95–98% of individuals with FRDA are homozygous for a GAA triplet repeat expansion in intron 1 of FXN. Approximately 2–5% of individuals with FRDA are compound heterozygotes with a GAA expansion in the disease-causing range in one FXN allele and a different FXN mutation of the other allele [1]. While most individuals with FRDA have the clinical findings noted above, phenotypic variation is well recog- nized and includes extremes in age of onset, FRDA with retained reflexes, and spastic paraparesis without ataxia [1]. We report here the clinical findings of an individual with FRDA due to compound heterozygosity of FXN mutations B. Diehl National Hospital for Neurology and Neurosurgery, London, UK M. S. Lee Department of Ophthalmology, University of Minnesota, Minneapolis, MN, USA J. R. Reid Radiology Institute, Cleveland Clinic, Cleveland, OH, USA C. D. Nielsen Medicine Institute, Cleveland Clinic, Cleveland, OH, USA M. R. Natowicz (*) Genomic Medicine Institute, NE-5 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA e-mail: natowim@ccf.org M. R. Natowicz Institutes of Pathology and Laboratory Medicine, Neurology and Pediatrics, Cleveland Clinic, Cleveland, OH, USA Neurogenetics (2010) 11:261–265 DOI 10.1007/s10048-009-0233-x