OMIM ID:
Optic Atrophy, Areflexia, Ataxia, Hearing Loss
Alternate Names
Defective Genes
Clinical Characteristics
Ocular 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.
Genetics
Inheritance
This 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 dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission