cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome

CAPOS syndrome is a rare autosomal dominant neurological disorder that primarily affects the cerebellum, peripheral nerves, and sensory organs. It is characterized by early onset cerebellar ataxia along with areflexia, progressive optic atrophy, sensorineural hearing impairment, and a pes cavus foot deformity. Pathogenic variants in the ATP1A3 gene disrupt normal neural function, leading to the observed symptoms. Although precise prevalence estimates are not available, the condition is considered very rare, affecting fewer than 1 in 1,000,000 people.

Individuals with CAPOS syndrome typically present with a range of neurological and sensory abnormalities. Early features include cerebellar ataxia, areflexia, and hypotonia, while hallmark findings such as undetectable visual evoked potentials, reduced consciousness, and optic atrophy lead to significant visual impairment. Sensorineural hearing loss, arm dystonia, postural instability, and episodic ataxia are also consistently observed with many patients, and additional features like nystagmus, gait ataxia, pes cavus, dysarthria, and even seizures appear in a subset of cases. Not all individuals experience all features, and severity varies considerably.

CAPOS syndrome is caused by pathogenic variants in the ATP1A3 gene, which is essential for maintaining the electrochemical gradients in neurons. Disruption of ATP1A3 function impairs normal neural signaling, resulting in the diverse neurological and sensory impairments seen in the condition. The disorder is inherited in an autosomal dominant pattern, meaning that an affected individual has a 50% chance of passing the mutation to their offspring. Genetic counseling is recommended for families to better understand the implications of this inheritance pattern and the variable expression of symptoms.

Currently, management of CAPOS syndrome focuses on supportive care and symptom management, as there are no specific foundational or targeted therapies available. Treatment is highly individualized and typically involves a multidisciplinary team approach, including physical therapy, occupational therapy, and other supportive interventions tailored to the patient’s needs. Regular surveillance is an essential part of long-term care, helping to identify potential complications at an early stage. Patients and families are encouraged to discuss treatment options with their healthcare team and to seek genetic counseling to understand the inheritance pattern and plan accordingly.

The course of CAPOS syndrome varies widely between individuals, with outcomes influenced by the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, many individuals manage their symptoms into adulthood, although the condition may progress, stabilize, or show a variable course over time. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists familiar with the condition for ongoing support and guidance.

Clinical trials are underway exploring new treatment approaches for CAPOS syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.