Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes: A clinical, biochemical and genetic study

Marianna Ciccolella, Michela Catteruccia, Sabina Benedetti, Isabella Moroni, Graziella Uziel, Chiara Pantaleoni, Luisa Chiapparini, Alberto Bizzi, Adele D'Amico, Fabiana Fattori, Maria Letizia Salsano, Anna Pastore, Giulia Tozzi, Fiorella Piemonte, Enrico Bertini

Research output: Contribution to journalArticlepeer-review


Brown-Vialetto-van Laere (BVVL) and Fazio-Londe (FL) are rare and clinically overlapping motor neurons syndromes. Recently BVVL has been associated with mutations in C20orf54/hRFT2 and defective riboflavin transport. We compared clinical and laboratory features of 6 patients (age range 11-17 years), with features of BVVL and FL overlap syndromes. Patients were assessed as following: blood levels of riboflavin and redox status, electrophysiological, neuroradiological and pulmonary studies, ALS functional rating scale and molecular genetic analysis. Two patients manifested deafness at ages of 3 and 10 years, and developed later subacute progressive ponto-bulbar palsy. A third patient markedly improved after intravenous immunoglobulins (IVIG), but then relapsed remaining unresponsive to treatment; he was not deaf although had abnormal auditory evoked responses (BAERs). The remaining 3 patients had no deafness, although likewise manifested subacute progressive ponto-bulbar palsy. We found hRFT2 mutations in 3/6 patients manifesting deafness or abnormal BAERs. No patient had reduced riboflavin blood levels. However, on riboflavin supplementation (10 mg/kg/day) the most severely affected BVVL patient stopped progression of symptoms following 8 months of treatment. BVVL and FL are severe progressive diseases with overlapping symptoms although only hRFT2 mutated patients manifest deafness. Riboflavin supplementation seems to stabilize and improve progression of the disease.

Original languageEnglish
Pages (from-to)1075-1082
Number of pages8
JournalNeuromuscular Disorders
Issue number12
Publication statusPublished - Dec 2012

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology


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