Axenfeld syndrome

Axenfeld syndrome
1a Microdontia and hypodontia. 1b Slit pupil and iris atrophy right eye. 1c Corectopia with iris atrophy left eye. 1d Posterior embryotoxon right eye. 1e Posterior embryotoxon left eye. 1f Broad peripheral anterior synechiae right eye.
Classification and external resources
ICD-9-CM	743.44
DiseasesDB	30800

Axenfeld syndrome (also known as Axenfeld-Rieger syndrome or Hagedoom syndrome) is a rare autosomal dominant^[1] disorder, which affects the development of the teeth, eyes, and abdominal region.

Eponym

It is named after the German ophthalmologist Theodor Axenfeld^[2][3] who studied anterior segment disorders, especially those such as Rieger Syndrome and the Axenfeld Anomaly.

The term "Rieger syndrome" is sometimes used to indicate an association with glaucoma.^[4] Rieger Syndrome is by medical definition determined by the presence of malformations of the teeth, the underdevelopment of the anterior segment of the eye, along with the manifestations caused by the Axenfeld anomaly.^[5] In addition to these occurrences, a prominent Schwalbe's line, an opaque ring around the cornea known as posterior embryotoxon, and hypoplasia of the iris can occur. Glaucoma occurs in up to 50% of patients with Axenfeld-Rieger Syndrome.^[6] Other defects such as a lower than average height and stature, a stunt in the development of the mid-facial features and mental deficiencies may be observed.

Diagnosis

Although most recognized for its correlation with the onset of glaucoma, the malformation is not limited to the eye, as Axenfeld syndrome when associated with the PITX2 genetic mutation usually presents congenital malformations of the face, teeth, and skeletal system.^[7]

The most characteristic feature affecting the eye is a distinct corneal posterior arcuate ring, known as an "embryotoxon".^[3] The iris is commonly adherent to the Schwalbe's line (posterior surface of the cornea).

Analysis of genetic samples from affected patients could result in the discovery of one of the three known genetic mutations which cause the syndrome. About 40% of Axenfeld-Rieger sufferers display mutations in one of the genes known as PAX6,^[8][9] PITX2 and FOXC1. ^[10]

The OMIM classification is as follows:

Type	OMIM	Gene
Type 1	180500	PITX2
Type 2	601499	possibly FOXO1A[11]
Type 3	602482	FOXC1
DeHauwere syndrome	109120	Unknown[12]

Detection of any of these mutations can give patients a clear diagnosis and post and antenatal procedures such as Preimplantation genetic diagnosis, Chorionic villus sampling and Amniocentesis can be offered to patients. From here, it is a decision for the prospective parent to decide whether they wish to use the genetic diagnosis that they have acquired to prevent the condition from being passed on to future generations.

Pathophysiology

Axenfeld syndrome has an autosomal dominant pattern of inheritance.

The molecular genetics of Axenfeld syndrome are poorly understood, and centers on three genes identified by cloning of chromosomal breakpoints from patients.

This disorder is inheritable as an autosomal dominant trait, which means the defective gene is located on an autosome, and only one copy of the gene is sufficient to cause the disorder when inherited from a parent who has the disorder. As shown in the diagram, this gives a 50/50 chance of offspring inheriting the condition from an affected parent.

See also

• Primary juvenile glaucoma
• SHORT syndrome
• Autosome
• Chorionic villus sampling
• Amniocentesis
• Preimplantation genetic diagnosis

References

1. Vieira, V; David, G; Roche, O; De, La, Houssaye, G; Boutboul, S; Arbogast, L; Kobetz, A; Orssaud, C; Camand, O; Schorderet, Df; Munier, F; Rossi, A; Delezoide, Al; Marsac, C; Ricquier, D; Dufier, Jl; Menasche, M; Abitbol, M (December 2006). "Identification of four new PITX2 gene mutations in patients with Axenfeld-Rieger syndrome" (Free full text). Molecular vision 12: 1448–60. PMID 17167399.
2. synd/1284 at Who Named It?
3. Axenfeld T (1920). "Embryotoxon cornea posterius". Berichte der Deutschen ophthalmologischen Gesellschaft 42: 301.
4. "eMedicine - Glaucoma, Secondary Congenital : Article by Inci Irak-Dersu". Archived from the original on 16 February 2008. Retrieved 2008-03-24.
5. "whonamedit - Rieger's Syndrome". Archived from the original on 6 April 2009. Retrieved 2009-03-06.
6. Yoko A Ito, Michael A Walter. Genomics and anterior segment dysgenesis: a review. Clinical and Experimental Ophthalmology 2014; 42: 13–24
7. Meyer-Marcotty, P; Weisschuh, N; Dressler, P; Hartmann, J; Stellzig-Eisenhauer, A (March 2008). "Morphology of the sella turcica in Axenfeld-Rieger syndrome with PITX2 mutation". Journal of Oral Pathology & Medicine 37 (8): 504–10. doi:10.1111/j.1600-0714.2008.00650.x. PMID 18331556.
8. "Rieger Syndrome and PAX6 Deletion". Retrieved 2009-03-06.
9. Riise R, Storhaug K, Brøndum-Nielsen K (April 2001). "Rieger syndrome is associated with PAX6 deletion". Acta Ophthalmol Scand 79 (2): 201–3. doi:10.1034/j.1600-0420.2001.079002201.x. PMID 11284764.
10. "Wikigenes - Disease relevance of PAX6". Retrieved 2009-03-06.
11. Phillips JC, del Bono EA, Haines JL; et al. (September 1996). "A second locus for Rieger syndrome maps to chromosome 13q14". Am. J. Hum. Genet. 59 (3): 613–9. PMC 1914897. PMID 8751862.
12. Lowry RB, Gould DB, Walter MA, Savage PR (June 2007). "Absence of PITX2, BARX1, and FOXC1 mutations in De Hauwere syndrome (Axenfeld-Rieger anomaly, hydrocephaly, hearing loss): a 25-year follow up". Am. J. Med. Genet. A 143A (11): 1227–30. doi:10.1002/ajmg.a.31732. PMID 17486624.

External links

• Axenfeld Rieger syndrome at NIH's Office of Rare Diseases
• Axenfeld Rieger anomaly with cardiac defects and sensorineural hearing loss at NIH's Office of Rare Diseases