Abstract

Brown-Vialetto-Van Laere syndrome (BVVL) is an exceptionally rare juvenile-onset motor neuron disease characterized by progressive ponto-bulbar palsy, sensorineural hearing loss, and multiple cranial nerve involvement, caused by mutations in riboflavin transporter genes SLC52A1, SLC52A2, and SLC52A3. Fewer than 90 cases have been documented in the literature to date. We report a familial case series of three siblings of Indian descent, born to non-consanguineous parents, presenting with bilateral lower motor neuron palsies involving cranial nerves VII, VIII, IX, X, and XII, progressive sensorineural hearing loss, dysarthria, dysphonia, and bilateral vocal cord paralysis. Notably, all three siblings reported a preceding febrile illness prior to symptom onset, a pattern previously described in the literature, though its pathophysiological significance remains uncertain. Markedly reduced plasma riboflavin levels were documented in all three patients. Clinical exome sequencing identified a heterozygous missense mutation in exon 2 of the SLC52A3 gene (chr20:g.746030A>T, p.Met130Lys) in all three siblings — a single allelic heterozygous mutation, which is an atypical and rarely symptomatic genotype. This case series is significant as it highlights that heterozygous single allelic SLC52A3 mutations can produce significant clinical manifestations, expands the phenotypic spectrum of BVVL in an Indian familial context, and underscores the critical importance of early genetic diagnosis. All three patients were initiated on high-dose riboflavin supplementation (200 mg twice daily), with the eldest reporting meaningful functional improvement. This report reinforces that timely recognition and treatment of BVVL can substantially alter disease trajectory.

Key words: Brown-Vialetto-Van Laere syndrome, Juvenile onset MND, Riboflavin transporter deficiency, Ponto-bulbar palsy, SLC52A3