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At a glance

A congenital neurologic syndrome that already presents in infancy. CAPOS is an acronym that stands for Cerebellar ataxia with Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss.

Synonyms

CAOS Syndrome (due to the fact that pes cavus is absent in approximately 70% of patients); Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, Sensorineural Hearing Loss Syndrome.

History

First described in 1996 in a mother and her two children by Paola Nicolaides, Richard Appleton, and Alan Fryer, physicians in the UK.

Incidence

Approximately 25 cases have been described to date. Both genders are equally affected.

Genetic inheritance

Autosomal dominant. The defect is caused by a c.2452G>A (p.Glu818Lys) mutation in the neuron-specific ATP1A3 (ATPase Na+/K+-transporting subunit alpha 3) gene that has been mapped to chromosome 19q13.2. The ATP1A3 encoded alpha-3 catalytic subunit of the Na+/K+-ATPase transmembrane ion pump is mainly expressed in the optic nerve, cochlea, cerebellar cortex, basal ganglia, hippocampus, and muscle-innervating nerve fibers, which could explain the characteristic signs of this disease.

Clinical aspects

A nonspecific recurrent febrile illness triggers an acute onset of cerebellar ataxia, often in combination with signs of encephalopathy/encephalitis and generalized hypotonia in previously healthy infants typically occurring between the age of 12 and 48 months (range 6 months to 7 years). Most patients (but not all) almost fully recover from the ataxia and encephalopathy between episodes. Other symptoms during acute episodes may include apathy/lethargy or coma, dysarthria, dysphagia, nystagmus, ophthalmoparesis (strabismus), and acute hearing and/or vision loss. It is noteworthy that three patients had a neurologic examination before their first febrile episode and already then showed mild symptoms of the disease (described as clumsiness, poor coordination, mild gait instability, and generalized areflexia). Most patients have between 1 and 3 such episodes in their lives and although they recover to some extent after each episode, they show a slow progression of the disease and eventually all will develop ataxia, areflexia, and sensorineural hearing loss and only one of all the reported patients does not suffer from optic atrophy, yet. Optic atrophy in this population is most likely slowly progressive over years and seems not to cause visual impairment in the initial stages. Fortunately, these patients remain mentally normal. Pes cavus is found in approximately 30% of patients. One patient experienced severe, step-wise exacerbations of her neurologic symptoms during each of her pregnancies and the immediate postpartum period. During the first pregnancy, her sensorineural hearing loss became progressively worse eventually requiring hearing aids, and during her second and third pregnancies, both, her vision and ataxia deteriorated significantly with her ending up being legally blind. She has had a total of six acute episodes of acute neurologic deterioration with the ...

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