Axenfeld-Rieger syndrome represents a spectrum of developmental disorders characterized by an anteriorly displaced Schwalbe line (posterior embryotoxon), with attached iris strands, iris hypoplasia, and anterior chamber dysgenesis; progression to glaucoma occurs during childhood or adulthood in 50% of cases (
Figs 18-3, 18-4, 18-5Fig 18-3,
Fig 18-4, and
Fig 18-5). The conditions, previously called Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis anomaly and syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia, all have genotypic and phenotypic overlap and are now considered a single entity known as Axenfeld-Rieger syndrome. With the identification of several causative genes and loci for these disorders, it is now known that there are cases in which the same ocular appearance is caused by different genes, and others in which very different ocular presentations, which previously would have been classified as distinct conditions (Peters anomaly, Rieger anomaly, or primary glaucoma, for example), are caused by the same mutated gene.
Axenfeld-Rieger syndrome may include a smooth, cryptless iris surface and a high iris insertion, sometimes accompanied by iris transillumination. Iris hypoplasia can range from mild stromal thinning to marked atrophy with hole formation, corectopia, and ectropion uveae. The severity of the iris hypoplasia may be so great as to mimic aniridia. Posterior embryotoxon, megalocornea (secondary to glaucoma), or microcornea may occur. Most important, glaucoma develops in 50% of cases. Associated nonocular abnormalities include small teeth, which may also be reduced in number; redundant periumbilical skin; hypospadias; and anomalies in the region of the pituitary gland.
Autosomal dominant inheritance is most common. Mutations in the PITX2 gene on band 4q25 have been identified. This is a paired homeobox gene that regulates expansion of other genes during embryonic development. Patients with mutations of PITX2 have been reported with phenotypes of aniridia, Peters anomaly, Rieger anomaly, and Axenfeld anomaly. The nonocular findings are actually more consistent and should be sought with any of these ocular phenotypes. Mutations in the forkhead transcription factor gene FOXC1 (formerly called FKHL7) also cause Axenfeld-Rieger syndrome, with features such as autosomal dominant iris hypoplasia, juvenile glaucoma, Rieger anomaly and syndrome, posterior embryotoxon, Peters anomaly, and primary congenital glaucoma. FOXC1 is also expressed in the heart, and some patients have cardiac valve abnormalities.
. Axenfeld-Rieger syndrome in the age of molecular genetics.2000;130(1):107–115.
, AldahmeshMA, Al-AmriA. Heterozygous FOXC1 mutation (M161K) associated with congenital glaucoma and aniridia in an infant and a milder phenotype in her mother.2008;29(2):67–71.
, KozlowskiK, WalterMA. Molecular genetics of Axenfeld-Rieger malformations.2002;11(10):1177–1184.
, LloydIC, Clayton-SmithJ, et al. Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations.2000;41(9):2456–2460.