P3.1 Brown–Vialetto–Van Laere and Fazio Londe overlap sindromes: A clinical, biochemical and genetic study in 6 patients

Brown-Vialetto-Van Laere Syndrome: Clinical and Neuropathologic Findings with Immunohistochemistry for C20orf54 in Three Affected Patients

“…Although studies of additional cases are required for definitive conclusions, the results suggest that in the right clinical setting, immunohistochemistry for the C20orf54 protein may eventually serve as a screening tool when selecting cases for sequencing of the C20orf54 gene to diagnose BVVLS at autopsy. Little is yet known about the function or importance of the genetic mutations or about their relation to riboflavin transport, although at least 1 study [10] has claimed riboflavin supplementation is able to stabilize and inhibit symptom progression. Loss of the normal punctate synaptic/axonal staining may be a primary consequence of the genetic mutation or may be related to secondary axonal degeneration, although the finding of such a pattern in the apparently unaffected cerebral cortex would argue for the former.…”

“…This latter fact has led to the use of riboflavin supplementation as a treatment to the disorder, with the apparent effect of cessation of symptom progression [9,10]. To date, fewer than 100 cases have been reported, mostly as clinical case reports in the neurology literature.…”

“…To date, fewer than 100 cases have been reported, mostly as clinical case reports in the neurology literature. Series with detailed neuropathologieal analysis of these cases, most of which involve young children, are very rare [6][7][8][9][10][11].…”

“…Recently, genetic analyses of a consanguineous family with multiple affected individuals with BVVLS have demonstrated mutations in the C20orf54 gene, which encodes the human homolog of a rat riboflavin transporter and is thought to play a role in riboflavin transport in human as well [7,8]. This latter fact has led to the use of riboflavin supplementation as a treatment to the disorder, with the apparent effect of cessation of symptom progression [9,10]. To date, fewer than 100 cases have been reported, mostly as clinical case reports in the neurology literature.…”

“…Specific affected areas/findings described include cranial nerves and cranial nerve nuclei III-XII, neuronal loss and gliosis in the substantiae nigrae, loci cerulei, inferior colliculi, subthalamic nuclei, solitary nuclei, cuneate and gracile nuclei, olivary nuclei, loss of cerebellar Purkinje neurons, loss of anterior horn spinal motor neurons, and degeneration of the spinocerebellar, central tegmental, solitary, and pyramidal tracts as well as the medial longitudinal fasciculus. The neurons of the neocortex, allocortex, and deep gray matter structures are spared [9][10][11][12][13].…”