Axenfeld-Rieger syndrome in the age of molecular genetics

Am J Ophthalmol. 2000 Jul;130(1):107-15. doi: 10.1016/s0002-9394(00)00525-0.


Purpose: To review the molecular genetics of Axenfeld-Rieger syndrome and related phenotypes and to discuss how this information might affect the way that we classify these disorders.

Methods: A review of historical and recent literature on Axenfeld-Rieger syndrome and related disorders. The review includes clinical and molecular genetic literature relevant to these phenotypes.

Results: Three chromosomal loci have recently been demonstrated to link to Axenfeld-Rieger syndrome and related phenotypes. These loci are on chromosomes 4q25, 6p25, and 13q14. The genes at chromosomes 4q25 and 6p25 have been identified as PITX2 and FKHL7, respectively. Mutations in these genes can cause a wide variety of phenotypes that share features with Axenfeld-Rieger syndrome. Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis anomaly, iridogoniodysgenesis syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia all have sufficient genotypic and phenotypic overlap that they should be considered one condition.

Conclusions: Axenfeld-Rieger syndrome is a term that can be used to describe a variety of overlapping phenotypes. To date, at least three known genetic loci can cause these disorders. The single most important feature of these phenotypes is that they confer a 50% or greater risk of developing glaucoma. Currently there is a fairly arbitrary grouping of disorders into small categories. Considering all of these phenotypes under the heading of Axenfeld-Rieger syndrome will allow easier communication between clinicians and scientists and eliminate arbitrary and confusing subclassification.

Publication types

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

MeSH terms

  • Anterior Eye Segment / abnormalities*
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 4 / genetics
  • Chromosomes, Human, Pair 6 / genetics
  • DNA-Binding Proteins / genetics
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / history
  • Forkhead Transcription Factors
  • Genetic Linkage
  • Glaucoma / genetics*
  • Glaucoma / history
  • History, 19th Century
  • History, 20th Century
  • Homeodomain Proteins / genetics
  • Humans
  • Intraocular Pressure / genetics
  • Iris / abnormalities*
  • Molecular Biology
  • Mutation
  • Nuclear Proteins*
  • Paired Box Transcription Factors
  • Phenotype
  • Syndrome
  • Transcription Factors / genetics


  • DNA-Binding Proteins
  • FOXC1 protein, human
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Nuclear Proteins
  • Paired Box Transcription Factors
  • Transcription Factors
  • homeobox protein PITX1
  • homeobox protein PITX3
  • homeobox protein PITX2