Axenfeld-Rieger Syndrome, Type 3

Clinical Characteristics

Ocular Features:

The most important ocular feature is glaucoma, found in greater than 50% of patients. It is frequently difficult to control and blindness is far too common. The ocular phenotype has many similar features found in type 1 [1] (RIEG1) but is discussed separately in this database since it is caused by a different mutation (see Axenfeld-Rieger syndrome, type 1 [1] for a full description of the phenotype). It has the typical findings of anterior segment dysgenesis including anterior displacement of Schwalbe's line, iris stromal hypoplasia, correctopia, and, of course, glaucoma.

Systemic Features:

Patients with this type of Axenfeld-Rieger disorder are less likely to have the systemic anomalies such as craniofacial and dental defects often seen in RIEG1 [1]. However, they often have a sensorineural hearing impairment and many have cardiac valvular and septal defects not usually seen in RIEG1 [1].

Genetics

This is an autosomal dominant disorder resulting from a mutation in the FOXC1 [2], a transcription factor gene located at 6p25. Mutations in the same gene also cause iris hypoplasia/iridogoniodysgenesis (IGDA) (IRID1 [3]) 601631 [4]) which is sometimes reported as a unique disorder but is either allelic or the same disorder as the type of Axenfeld-Rieger syndrome discussed here.

Type 1 Axenfeld-Rieger syndrome [1] (180500 [5]) results from mutations in the PITX1 [6] transcription factor gene and type 4 from mutations in PRDM5 [7], also a transcription factor gene. However, digenic cases have also been reported with mutations in both PITX1 and FOXC1 [2] genes.

The mutation responsible for t [8]ype 2 Axenfeld-Rieger syndrome [8] [8](601499 [9]) has as yet not been identified. Diagnosis is best made by ruling out mutations in PITX1 [6] and FOXC1 [2] although it is claimed that maxillary hypoplasia and umbilical defects are less common in type 2.

Treatment

Treatment Options:

All patients with Axenfeld-Rieger syndromes must be monitored and treated for glaucoma throughout their lives.

References

Article Title:

Axenfeld-Rieger syndrome [10]

Seifi M, Walter MA. Axenfeld-Rieger syndrome. Clin Genet. 2017 Oct 3. doi: 10.1111/cge.13148. [Epub ahead of print] Review.

PubMed ID:

28972279

Digenic inheritance in axenfeld rieger syndrome [11]

Weisschuh N. Digenic inheritance in axenfeld rieger syndrome. Hum Mutat. 2011 Oct;32(10):iv. doi: 10.1002/humu.21593.

PubMed ID:

21932364

Axenfeld-Rieger syndrome in the age of molecular genetics [12]

Alward WL. Axenfeld-Rieger syndrome in the age of molecular genetics. Am J
Ophthalmol. 2000 Jul;130(1):107-15. Review.

PubMed ID:

11004268

Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations [13]

Tumer Z, Bach-Holm D. Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur J Hum Genet. 2009 Dec;17(12):1527-39.

PubMed ID:

19513095