CAPOS Syndrome

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Article initiated by:

Aroucha Vickers, DO

All contributors:

Aroucha Vickers, DO, Sannah Vasaya, Kendall Chaffin, Nagham Al-Zubidi, MD, Aroucha Vickers, DO

Assigned editor:

Nagham Al-Zubidi, MD

Review:

Assigned status Update Pending

 by Nagham Al-Zubidi, MD on May 16, 2024.

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Contributing Editors:	add

Disease Entity

Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome is a rare chronic neurological disorder named for its unique constellation of symptoms.

History

CAPOS syndrome was first described in the literature in 1996 by Nicoladies when three family members were found to each have early onset cerebellar ataxia, progressive optic atrophy, areflexia, and a pes cavus deformity. Having no clear etiology, Nicoladies described this constellation of symptoms as “a separate syndrome of early onset cerebellar ataxia with associated features (cerebellar ataxia plus)”.

Epidemiology

The number of people with CAPOS disease is estimated to be fewer than 1,000. As of 2020, 33 cases of CAPOS syndrome have been reported in the English literature. Symptoms of this disease may begin as early as infancy.

Etiology 

CAPOS syndrome is caused by a mutation in the ATP1A3 gene on chromosome 19q13 which affects the alpha-3 polypeptide of ATPase, Na+/K+ transporte. This leads to a distortion of electrochemical gradients across membranes.

Diagnosis of CAPOS syndrome can be made clinically or by identifying the ATP1A3 variant on genotyping. ATP1A3 variants can be inherited or occur de novo, meaning that a family history is not required to make the diagnosis. CAPOS syndrome is inherited in an autosomal dominant fashion, meaning that each child of an affected individual has a 50% chance of inheriting the disease. Prenatal testing for fetuses is possible.

ATP1A3 mutations are associated with three neurological disorders; CAPOS syndrome, rapid onset dystonia parkinsonism, and alternating hemiplegia of childhood. There is consideration that these represent a clinical spectrum of disorders. Unifying features include an abrupt onset of symptoms in the presence of triggering factors and an asymmetric anatomical distribution.

Diagnosis

Symptoms

Cerebellar Ataxia	Loss of coordination of muscle movement due to inflammation of the cerebellum
Areflexia	Absence of deep tendon reflexes
Pes Cavus	High arched feet
Optic Atrophy	Death of the retinal ganglion cell axons that comprise the optic nerve
Sensorineural hearing loss	Hearing loss resulting from damage to the inner ear or auditory nerve

Other less common symptoms may include the following: hypotonia or dystonia, myoclonus, bradykinesia, irregular eye movements (nystagmus or strabismus), dysarthria (difficulty speaking), dysphagia (difficulty swallowing), hyporeflexia (decreased reflexes), autistic behavior, intellectual disability, cardiac conduction blocks, and cognitive impairment. Loss of consciousness, seizure, or onset of coma may occur during an episode in rare circumstances.

Ocular Manifestations

Progressive vision loss due to optic atrophy or episodic abnormal eye movements such as nystagmus or strabismus may be observed.

Disease Progression

Symptoms are typically triggered by an infection-induced fever or childbirth. Initial manifestations of CAPOS syndrome are typically episodic ataxia and encephalopathy. Sensorineural hearing loss and optic atrophy may occur at onset or later in the course of the disease. Although symptoms typically resolve once the infection has cleared, neurologic sequelae of the disease such as movement problems, vision loss, and hearing loss may persist. Permanence of these symptoms vary. People diagnosed with CAPOS syndrome experience 1-3 episodes on average during their lifetime.

Management

There is no definitive treatment for CAPOS syndrome. Treatment primarily focuses on symptomatic control and preventative measures. For movement-related symptoms, physical, occupational, and speech therapy are recommended. Vision and hearing loss are controlled with standard treatment. Preventative measures include avoiding triggers that can lead to acute attacks as well as the following medications and countermeasures: flunarizine, topiramate, a ketogenic diet, and sleep. Additionally, Acetazolamide may be considered to prevent episodes of ataxia. Being a carbonic anhydrase inhibitor, acetazolamide creates a state of metabolic acidosis which reduces ion leakage and may normalize neuron excitability. Case studies however have shown limited success.