chorea-acanthocytosis

Chorea-acanthocytosis, also known as CHAC or Levine-Critchley syndrome, is a neurological condition that belongs to the neuroacanthocytosis spectrum and is characterized by progressive movement disturbances and psychiatric manifestations. Affected individuals typically experience a range of symptoms including involuntary movements, dysarthria, and behavioral changes such as self-mutilation of the tongue and lips. The condition is caused by pathogenic variants in the VPS13A gene, which plays a crucial role in normal cellular function. Because precise prevalence estimates are not available, chorea-acanthocytosis is considered rare and exhibits considerable variability in its clinical course.

The clinical presentation of chorea-acanthocytosis is dominated by persistent neurological features. Nearly all affected individuals exhibit dysarthria, chorea, orofacial dyskinesia, and self-mutilation behaviors affecting the tongue and lips due to involuntary movements. Other consistent findings include lateral ventricle dilatation, caudate atrophy, peripheral axonal neuropathy, hypotonia, and dysphagia. In addition, psychiatric and behavioral issues such as apathy, depression, anxiety, and bruxism are frequently reported. Some individuals may also experience variable features including elevated levels of lactate dehydrogenase and creatine kinase, as well as bilateral tonic-clonic seizures and, in a subset, dementia. Not all individuals experience every feature, and severity varies widely between individuals.

Chorea-acanthocytosis is caused by pathogenic variants in the VPS13A gene. This gene is essential for maintaining normal cellular function, and disruption in its activity is associated with both the neurological and hematological abnormalities observed in the condition. The disorder follows an autosomal recessive inheritance pattern, which means that an affected individual must inherit two altered copies of VPS13A—one from each parent. As a result, parents who carry a single mutated copy are typically asymptomatic, while each sibling of an affected individual has a 25% chance of being affected. Families are encouraged to consider genetic counseling to understand these risks and explore family planning options.

Currently, management of chorea-acanthocytosis centers on supportive care and symptom management, as there are no FDA-approved or targeted treatments available. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include neurologists, psychiatrists, and physical therapists to address movement disturbances, speech difficulties, and behavioral changes. Regular surveillance is an essential part of long-term care, as ongoing monitoring can help detect complications early and inform timely interventions. Additionally, genetic counseling is recommended to help patients and their families understand the condition and explore appropriate management strategies.

The course of chorea-acanthocytosis is highly variable between individuals. Although many affected individuals experience a progressive decline in neurological function, the rate of symptom progression can differ significantly, with some experiencing periods of relative stabilization. With current standards of care and a focus on supportive management, many individuals live into adulthood and sustain a quality of life that can be improved with early intervention and ongoing care. Outcomes described in medical literature continue to evolve as standards of care improve, and patients are encouraged to work closely with specialists and genetic counselors to navigate the uncertainties and tailor management to their specific needs.