Cerebellar Ataxia, Impaired Intellectual Development, and Disequilibrium Syndrome-2: A Case Report

Area of Science:

• Genetics and rare diseases
• Neurodevelopmental disorders

Background:

• Cerebellar ataxia, intellectual disability, and disequilibrium syndrome-2 (CAMRQ2) is a rare genetic disorder.
• Pathogenic variants in the WDR81 gene are associated with CAMRQ2, typically presenting with congenital cerebellar ataxia and intellectual disability.

Observation:

• A mildly affected female from a non-consanguineous family presented with developmental delays, feeding difficulties, and unsteady gait.
• Initial diagnostic evaluations, including brain MRI and genetic testing, were nondiagnostic.
• Reanalysis of genetic data at age five identified a homozygous pathogenic WDR81 variant.

Findings:

• The identified WDR81 variant expands the known clinical spectrum of CAMRQ2.
• The patient exhibits cerebellar ataxia and hypotonia, with academic progress supported by tutoring.
• This case demonstrates the value of iterative genetic testing in diagnosing rare conditions.

Implications:

• Highlights the phenotypic variability of CAMRQ2.
• Underscores the importance of considering WDR81 variants in patients with cerebellar ataxia, irrespective of consanguinity.
• Emphasizes the utility of periodic re-evaluation of genetic data for diagnosing rare and complex disorders.