cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2

Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 is a neurodevelopmental condition that primarily affects coordination, balance, and cognitive functioning. It is caused by mutations in the WDR81 gene, which plays an important role in normal brain development. The condition typically presents in early childhood with global developmental delay and challenges in motor skills such as walking and maintaining balance. Although specific prevalence data are not available, the consistent presence of features such as cerebellar atrophy and intellectual impairment makes the diagnosis recognizable among affected individuals.

Individuals with this condition most commonly exhibit global developmental delay and cerebellar atrophy, which are observed in every affected person. Early clinical features include delays in walking and difficulties with motor coordination, often manifested as a broad-based gait and ataxia. In addition, many experience cognitive challenges and may show signs of intention tremor and sensorineural hearing impairment, although these features can vary in severity. Not all individuals experience all of these features, and severity varies considerably.

This condition is caused by pathogenic variants in the WDR81 gene. The WDR81 gene is essential for proper neurological development, and mutations in this gene disrupt normal brain structure and function. It is inherited in an autosomal recessive pattern, meaning that both parents typically carry one copy of the altered gene. As a result, each pregnancy has a 25% chance of resulting in an affected child, and genetic counseling is recommended for families.

Currently, management focuses on supportive care and symptom management as there are no specifically approved treatments for this condition. Treatment is tailored to the individual, typically involving a multidisciplinary team to address motor difficulties, cognitive challenges, and communication needs. Supportive therapies such as physical therapy, occupational therapy, and specialized educational interventions can help maximize functional abilities. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to assist with family planning and management decisions.

The condition is lifelong, and outcomes vary depending on symptom severity, age at diagnosis, and access to multidisciplinary care. With current standards of supportive care, many individuals benefit from interventions that help improve quality of life, although challenges related to motor coordination and cognitive functioning may persist. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists, including genetic counselors, to explore support networks and gain further guidance.