Brown-Vialetto-Van Laere syndrome: clinical and neuropathologic findings with immunohistochemistry for C20orf54 in three affected patients.

Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare degenerative neurological disorder characterized by pontobulbar palsy and sensorineural deafness. Since its initial description in 1894, fewer than 100 cases have been reported, and published neuropathological analyses of these cases are extremely rare. Recently, individuals with BVVLS have been found to carry mutations in the C20orf54 gene, which encodes the human homolog for a rat riboflavin transporter. We present the case of a male who presented at the age of 5 years with sensorineural deafness, as well as those of 2 infant sisters who presented at 11 and 13 months of age with weakness and ataxia, respectively. All cases were genetically confirmed. We include the 1st immunohistochemical characterization of C20orf54 expression in BVVLS and controls. Results showed punctate axonal staining in the control cases that was dramatically reduced in the 3 BVVLS cases compared to the 5 controls. This decreased staining was seen even in the neocortex, which was unaffected in the BVVLS cases by routine histology. While the implications of these results are far from definitive, and although the evaluation of more cases is needed, immunohistochemistry for the C20orf54 protein may eventually be useful, in the right clinical scenario, as a screening test when selecting cases for sequencing of the C20orf54 gene to diagnose BVVLS at autopsy.