Recent advances in bulbar syndromes: genetic causes and disease mechanisms

Curr Opin Neurol. 2014 Oct;27(5):506-14. doi: 10.1097/WCO.0000000000000133.


Purpose of review: With advances in next-generation gene sequencing, progress in deep phenotyping and a greater understanding of the pathogenesis of motor neuron disease, our knowledge of the progressive bulbar syndromes has significantly increased in recent years. This group of heterogeneous conditions, in which the primary disorder is focused around degeneration of the lower cranial nerves, can occur in children or adults and form a spectrum of severity, based around the common feature of bulbar dysfunction. Early genetic diagnosis may allow treatment in some bulbar syndromes.

Recent findings: Brown-Vialetto-Van Laere and Fazio-Londe syndromes are the most recent childhood forms of progressive bulbar palsy to be genetically defined. The clinical phenotype of this group of childhood disorders was first reported over 120 years ago. Recently, it was demonstrated that in a third of these patients Brown-Vialetto-Van Laere is caused by mutations in the SLC52A2 and SLC52A3 genes, both of which encode riboflavin transporters. Importantly, supplementation of riboflavin can lead to significant clinical improvement if started early in the disease process.

Summary: Here, we outline the clinical features, management and an update on the disease mechanisms and genetic causes of the progressive bulbar syndromes.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bulbar Palsy, Progressive / drug therapy*
  • Bulbar Palsy, Progressive / genetics*
  • Bulbar Palsy, Progressive / history
  • Bulbar Palsy, Progressive / physiopathology
  • Disease Management
  • Heat-Shock Proteins / genetics*
  • History, 19th Century
  • Humans
  • Mutation / genetics*
  • Phenotype
  • Riboflavin / therapeutic use
  • Sodium-Glucose Transporter 2 / genetics*
  • Symporters / genetics*
  • Vitamin B Complex / therapeutic use


  • Heat-Shock Proteins
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Symporters
  • Vitamin B Complex
  • SLC5A3 protein, human
  • Riboflavin