Predominantly Cone-System Dysfunction as Rare Form of Retinal Degeneration in Patients With Molecularly Confirmed Bardet-Biedl Syndrome

Am J Ophthalmol. 2015 Aug;160(2):364-372.e1. doi: 10.1016/j.ajo.2015.05.007. Epub 2015 May 15.


Purpose: To describe a series of patients with Bardet-Biedl syndrome (BBS) and predominantly retinal cone dysfunction, a previously only rarely reported association.

Design: Retrospective observational case series.

Methods: Seven patients with clinically proven Bardet-Biedl syndrome had undergone detailed ocular phenotyping, which included fundus examination, Goldmann visual fields, fundus autofluorescence imaging (FAF), optical coherence tomography (OCT), and electroretinography (ERG). Mutational screening in the BBS genes was performed either by direct Sanger sequencing or targeted next-generation sequencing.

Results: All 7 patients had proven BBS mutations; 1 had a cone dystrophy phenotype on ERG and 6 had a cone-rod pattern of dysfunction. Macular atrophy was present in all patients, usually with central hypofluorescence surrounded by a continuous hyperfluorescent ring on fundus autofluorescence imaging. OCT confirmed loss of outer retinal structure within the atrophic areas. No clear genotype-phenotype relationship was evident.

Conclusions: Patients with Bardet-Biedl syndrome usually develop early-onset retinitis pigmentosa. In contrast, the patients described herein, with molecularly confirmed Bardet-Biedl syndrome, developed early cone dysfunction, including the first reported case of a cone dystrophy phenotype associated with the disorder. The findings significantly expand the phenotype associated with Bardet-Biedl syndrome.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bardet-Biedl Syndrome / complications*
  • Bardet-Biedl Syndrome / genetics
  • DNA / genetics*
  • DNA Mutational Analysis
  • Electroretinography
  • Eye Proteins / genetics*
  • Female
  • Fluorescein Angiography
  • Fundus Oculi
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Degeneration / etiology*
  • Retinal Degeneration / genetics
  • Retinal Degeneration / physiopathology
  • Retrospective Studies
  • Tomography, Optical Coherence
  • Visual Acuity
  • Visual Fields


  • Eye Proteins
  • DNA