Optic Atrophy, Areflexia, Ataxia, Hearing Loss Clinical CharacteristicsOcular Features: Progressive optic atrophy is a consistent feature of all reported cases. It may have its onset during the first year or two of life but always before the age of 10 years. Nystagmus may be seen early during acute febrile episodes but eventually becomes permanent. Systemic Features: Onset of neurological symptoms usually occurs in childhood during or following an acute febrile illness which may be recurrent. This may consist of cerebellar ataxia, hypotonia, drowsiness, dysarthria, and lethargy. There may be partial or full recovery following the febrile illness initially but some signs remain after subsequent episodes. Areflexia and sensorineural deafness can be additional signs and pes cavus eventually appears. The acute febrile episodes tend to decrease in time along with the progression of neurological signs. Plantar responses remain normal while peripheral neuropathy and seizures are not consistent features. MRI imaging of the brain is normal. Cognitive function usually remains normal but some children have autism features and social adjustment problems have been noted. GeneticsThis is an autosomal dominant condition (which may be considered a form of ‘ataxia-plus’) secondary to heterozygous mutations in the ATP1A3 gene (19q13.31). The protein product is a subunit of an ATPase enzyme primarily active in neural tissue. Other mutations in the same gene have been found in dystonia-12 and alternating hemiplegia of childhood. Pedigree: Autosomal dominantTreatmentTreatment Options: No treatment is known for this condition but physical therapy and mobility-assistive devices may be helpful. Low vision aids may be useful as well. ReferencesArticle Title: A novel recurrent mutation in ATP1A3 causes CAPOS syndrome Demos MK, van Karnebeek CD, Ross CJ, Adam S, Shen Y, Zhan SH, Shyr C, Horvath G, Suri M, Fryer A, Jones SJ, Friedman JM; FORGE Canada Consortium. A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet J Rare Dis. 2014 Jan 28;9:15. PubMed ID: 24468074 Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome Nicolaides P, Appleton RE, Fryer A. Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome. J Med Genet. 1996 May;33(5):419-21.. PubMed ID: 8733056 Read more about Optic Atrophy, Areflexia, Ataxia, Hearing Loss
A novel recurrent mutation in ATP1A3 causes CAPOS syndrome Demos MK, van Karnebeek CD, Ross CJ, Adam S, Shen Y, Zhan SH, Shyr C, Horvath G, Suri M, Fryer A, Jones SJ, Friedman JM; FORGE Canada Consortium. A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet J Rare Dis. 2014 Jan 28;9:15. PubMed ID: 24468074
Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome Nicolaides P, Appleton RE, Fryer A. Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome. J Med Genet. 1996 May;33(5):419-21.. PubMed ID: 8733056
