CAPOS syndrome is a rare genetic neurological disorder which is characterized by abnormalities of the feet, eyes and brain which affect their normal function. These symptoms occur episodically when a fever-related infection is present within the body. The name is an acronym for "cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss".

Signs and symptoms

Usually, individuals with this condition have cerebellar ataxia,

areflexia Hyporeflexia is the reduction or absence of normal bodily reflexes. It can be detected through the use of a reflex hammer and is the opposite of hyperreflexia. Hyporeflexia is generally associated with a deficit in the lower motor neurons (at t ...

, high-arched feet, optic nerve wasting/degeneration, sensorineural

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is writte ...

. These symptoms have variable onset, but they generally begin episodically after having a

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

-causing infection such as the

common cold The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...

, manifesting mainly as sudden-onset ataxic episodes and

encephalopathy Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...

. Other triggers include

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

and giving birth. Other symptoms that occur during the episodic ataxia includes

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) Eye movement (sensory), eye movement. People can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in visual impairment, re ...

strabismus Strabismus is an eye disorder in which the eyes do not properly align with each other when looking at an object. The eye that is pointed at an object can alternate. The condition may be present occasionally or constantly. If present during a ...

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. It is a condition in which problems effectively occur with the ...

dysphagia Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...

hyporeflexia Hyporeflexia is the reduction or absence of normal bodily reflexes. It can be detected through the use of a reflex hammer and is the opposite of hyperreflexia. Hyporeflexia is generally associated with a deficit in the lower motor neurons (at ...

, and temporary deafness. More serious symptoms include

loss of consciousness Unconsciousness is a state in which a living individual exhibits a complete, or near-complete, inability to maintain an awareness of self and environment or to respond to any human or environmental stimulus. Unconsciousness may occur as the re ...

and/or onset of a

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...

. These symptoms usually improve alongside the illness that caused the fever. General frequency of episodes with people suffering from CAPOS syndrome is 1-3.

Complications

There are various complications associated with the disorder, some of them include

vision impairment Visual or vision impairment (VI or VIP) is the partial or total inability of visual perception. In the absence of treatment such as corrective eyewear, assistive devices, and medical treatment, visual impairment may cause the individual difficul ...

/blindness due to

optic atrophy Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain. Damage and death of these nerve cells, or neurons, leads to characteristic featu ...

characteristic of the disorder,

due to atrophy of the nerves that aid in hearing, problems with walking due to the ataxia, etc.

Causes

This condition is caused by autosomal dominant

missense mutations In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Missense mutations change amino acids, which in turn al ...

in the

ATP1A3 Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ''ATP1A3'' gene. Function The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of ...

gene, in

chromosome 19 Chromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 61.7 million base pairs, the building material of DNA. It is considered the most Gene density, gene-ri ...

. The mutation is thought to be gain-of-function.

Epidemiology

According to OMIM, only 14 cases have been described in medical literature.

History

This condition was first discovered in 1996 by Nicolaides et al. when they described a mother and two siblings (brother and sister) with (summarized) early-onset reoccurring cerebellar ataxia and progressive optic atrophy accompanied by sensorineural deafness.

References

{{reflist Rare genetic syndromes Syndromes with sensorineural hearing loss Syndromes affecting the optic nerve Autosomal dominant disorders Episodic and paroxysmal disorders