CANVAS syndrome is a rare neurological disorder that affects multiple body systems, including the brain, spinal cord, and nerves. It is characterized by its progressive nature, meaning symptoms worsen over time.
Understanding CANVAS Syndrome
CANVAS is an acronym for Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome. Cerebellar ataxia refers to problems with muscle coordination due to issues in the cerebellum. This can manifest as an unsteady gait, stumbling, and difficulty with balance. Individuals may also experience challenges with fine motor control, such as writing or eating, and slow, slurred speech.
Neuropathy involves problems with nerves that transmit signals about sensation. This can lead to numbness, tingling, or burning sensations in the hands and feet. It also impacts proprioception, the body’s ability to sense its position and movement, which further affects balance.
Vestibular areflexia indicates that reflexes related to balance from the inner ear’s vestibular system are not functioning correctly. This often results in a loss of balance and an unsteady feeling when walking or standing. Some individuals may experience blurry or jumpy vision, known as oscillopsia, especially when their head moves.
Beyond these core components, other common features include a chronic, unexplained cough, which can appear decades before other neurological symptoms. Autonomic dysfunction can also occur, leading to issues like sudden drops in blood pressure upon standing, chronic constipation, urinary difficulties, or altered sweating. The severity and combination of symptoms can vary among individuals, even within the same family.
The Genetic Cause
CANVAS syndrome is a genetic disorder. The primary cause identified for CANVAS is a specific mutation in the RFC1 gene. This mutation involves a biallelic AAGGG pentanucleotide repeat expansion located in an intron of the gene. While healthy RFC1 genes typically have AAAAG repeats, in CANVAS, the ratio of A and G is altered, leading to an expansion of AAGGG repeats.
For a diagnosis of CANVAS, an individual typically has over 400 AAGGG repeats in the RFC1 gene. This condition follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated RFC1 gene—one from each parent—to develop the syndrome.
Parents who carry one copy of the mutated gene are typically asymptomatic, but they can pass it on to their children. If both parents are carriers, each child has a 25% chance of inheriting two copies of the mutated gene and developing CANVAS syndrome. They also have a 50% chance of being an asymptomatic carrier like their parents, and a 25% chance of being unaffected and not a carrier.
Identifying and Tracking the Syndrome
Diagnosing CANVAS syndrome typically begins with a thorough clinical evaluation by a neurologist, who assesses symptoms consistent with the condition. Given the varied symptoms, further diagnostic tests are often tailored to the individual. Genetic testing for the RFC1 gene mutation is the definitive method for confirming a CANVAS diagnosis. These pathogenic expansions cannot be detected by standard sequencing methods like exome sequencing but can be suspected by genome sequencing.
Neuroimaging, such as an MRI of the brain, is often performed and may reveal cerebellar atrophy. This atrophy can be subtle in early stages and may even precede the onset of cerebellar symptoms. Nerve conduction studies can identify neuropathy by assessing nerve function, while vestibular function tests evaluate the inner ear’s balance system. Audiometry may also be used to assess hearing, though hearing is typically unaffected in CANVAS syndrome.
The average age of symptom onset is around 50 years, but it can range widely from the early 20s to the 70s. Early signs can be subtle, such as a chronic cough or minor sensory changes, and it may take decades for balance problems to become prominent enough for individuals to seek medical attention. The rate of progression can vary among individuals, but it generally proceeds slowly.
Supportive Care and Management
Currently, there is no treatment that can reverse or halt the progression of CANVAS syndrome. Management focuses on alleviating symptoms and improving an individual’s quality of life through supportive care. This often involves a multidisciplinary approach with therapies tailored to specific symptoms.
Physical therapy is a common intervention to address ataxia and balance issues, helping to improve walking, strength, and endurance. Occupational therapy assists individuals in adapting to daily living activities affected by the syndrome. Speech therapy can aid those experiencing dysarthria (slurred speech) and dysphagia (swallowing difficulties).
Vestibular rehabilitation, an exercise-based therapy, helps the brain compensate for the impaired signals from the inner ear’s balance system. This may include exercises to reduce symptoms that occur with head movements. For hearing loss, hearing aids can be used. Medications may also be prescribed to manage specific symptoms, such as neuropathic pain, chronic cough, or orthostatic hypotension (sudden drops in blood pressure).