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

Pathogenic variants in the WDR81 gene on chromosome 17p13.3 have been linked to cerebellar ataxia, impaired intellectual development, and disequilibrium syndrome-2 (CAMRQ2), a rare disorder characterized by congenital cerebellar ataxia (a condition causing impaired coordination and balance due to cerebellar dysfunction), intellectual disability, and gait abnormalities. Additional features include thoracic kyphosis, scoliosis, short stature, intention tremor, and cerebellar atrophy. We present a case of a mildly affected female from a non-consanguineous family, expanding the clinical spectrum of this disorder. The patient, born at term as part of a dizygotic-diamniotic twin pregnancy, exhibited developmental delays, feeding difficulties, and unsteady gait. This case highlights the importance of iterative genetic testing, as initial evaluations, including brain MRI and genetic testing, were nondiagnostic. However, reanalysis at age five identified a homozygous pathogenic variant in WDR81, demonstrating how periodic re-evaluation of genetic data can aid in diagnosing rare disorders that may have been previously unrecognized. The patient continues to experience cerebellar ataxia and hypotonia, characterized by decreased muscle tone and reduced strength, with no other major medical conditions. She receives physical and occupational therapies and is academically at grade level with tutoring support. This case highlights the phenotypic variability of CAMRQ2 and underscores the importance of considering WDR81 variants in patients with cerebellar ataxia, even in the absence of consanguinity.