Axenfeld syndrome

Axenfeld syndrome
a) Microdontia and hypodontia. b) Slit pupil and iris atrophy right eye. c) Corectopia with iris atrophy left eye. d) Posterior embryotoxon right eye. e) Posterior embryotoxon left eye. f) Broad peripheral anterior synechiae right eye.^[1]
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^[2] disorder, which affects the development of the teeth, eyes, and abdominal region.^[3]

Eponym

It is named after the German ophthalmologist Theodor Axenfeld^[4]^[5] who studied anterior segment disorders, especially those such as Rieger Syndrome and the Axenfeld Anomaly.

Axenfeld-Rieger syndrome is characterized by abnormalities of the eyes, teeth, and facial structure.^[6] Rieger Syndrome, by medical definition, is determined by the presence of malformed teeth, underdeveloped anterior segment of the eyes, and cardiac problems associated with the Axenfeld anomaly.^[7] The term "Rieger syndrome" is sometimes used to indicate an association with glaucoma.^[8] Glaucoma occurs in up to 50% of patients with Rieger Syndrome. Glaucoma develops during adolescence or late-childhood, but often occurs in infancy.^[5]^[9] In addition, a prominent Schwalbe's line, an opaque ring around the cornea known as posterior embryotoxon, may arise with hypoplasia of the iris.^[10] Below average height and stature, stunted development of the mid-facial features and mental deficiencies may also be observed in patients.^[10]

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.^[8]

The most characteristic feature affecting the eye is a distinct corneal posterior arcuate ring, known as an "embryotoxon".^[5] The iris is commonly adherent to the Schwalbe's line (posterior surface of the cornea).

Diagnosis One of the three known genetic mutations which cause Rieger Syndrome can be identified through genetic samples analysis. About 40% of Axenfeld-Rieger sufferers display mutations in one of the three genes known as PAX6,[8][9] PITX2 and FOXC1. The difference between Type 1, 2, and 3 Axenfeld Syndrome is the genetic cause, all three types display the same symptoms and abnormalities.^[6]

The OMIM classification is as follows:

Type	OMIM	Gene
Type 1	180500	PITX2
Type 2	601499	possibly FOXO1A^[7]
Type 3	602482	FOXC1
DeHauwere syndrome	109120	Unknown^[9]

Detection of any of these mutations can give patients a clear diagnosis and prenatal procedures such as preimplantation genetic diagnosis, Chorionic villus sampling and Amniocentesis can be offered to patients and prospective parents.^[11]

Pathophysiology

Axenfeld syndrome has an autosomal dominant pattern of inheritance.^[12]

The molecular genetics of Axenfeld syndrome are poorly understood, but centers on three genes identified by cloning of chromosomal breakpoints from patients.^[10]^[13]

This disorder is inheritable as an autosomal dominant trait,^[12] 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.

References

↑ Dhir, L; Frimpong-Ansah, K; Habib, Nabil E (2008). "Missed case of Axenfeld-Rieger syndrome: a case report". Cases Journal. 1 (1): 299. doi:10.1186/1757-1626-1-299. PMC 2585579. PMID 18990239.
↑ Vieira, Véronique; David, Gabriel; Roche, Olivier; de la Houssaye, Guillaume; Boutboul, Sandrine; Arbogast, Laurence; Kobetz, Alexandra; Orssaud, Christophe; Camand, Olivier; Schorderet, Daniel F.; Munier, Francis; Rossi, Annick; Delezoide, Anne Lise; Marsac, Cécile; Ricquier, Daniel; Dufier, Jean-Louis; Menasche, Maurice; Abitbol, M. (2006). "Identification of four new PITX2 gene mutations in patients with Axenfeld-Rieger syndrome". Molecular Vision. 12: 1448–60. PMID 17167399.
↑ Fitch, Naomi; Kaback, Martin (1978). "The Axenfeld syndrome and the Rieger syndrome". Journal of Medical Genetics. 15 (1): 30–4. doi:10.1136/jmg.15.1.30. PMC 1012820. PMID 416212.
↑ synd/1284 at Who Named It?
1 2 3 Axenfeld, T (1920). "Embryotoxon cornea posterius". Berichte der Deutschen ophthalmologischen Gesellschaft. 42: 301–2.
1 2 "Axenfeld-Rieger syndrome". United States Department of Health and Human Services. November 8, 2016.
1 2 Phillips, Jeffrey C.; del Bono, Elizabeth A.; Haines, Jonathan L.; Pralea, Anca Madalina; Cohen, John S.; Greff, Linda J.; Wiggs, Janey L. (1996). "A second locus for Rieger syndrome maps to chromosome 13q14". American Journal of Human Genetics. 59 (3): 613–9. PMC 1914897. PMID 8751862.
1 2 Meyer-Marcotty, P.; Weisschuh, N.; Dressler, P.; Hartmann, J.; Stellzig-Eisenhauer, A. (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.
1 2 Lowry, R. Brian; Gould, Douglas B.; Walter, Michael A.; Savage, Paul R. (2007). "Absence of PITX2, BARX1, and FOXC1 mutations in De Hauwere syndrome (Axenfeld–Rieger anomaly, hydrocephaly, hearing loss): A 25-year follow up". American Journal of Medical Genetics Part A. 143A (11): 1227–30. doi:10.1002/ajmg.a.31732. PMID 17486624.
1 2 3 Suzuki, Katsuhiro; Nakamura, Makoto; Amano, Emi; Mokuno, Kumiko; Shirai, Shoichiro; Terasaki, Hiroko (2006). "Case of chromosome 6p25 terminal deletion associated with Axenfeld–Rieger syndrome and persistent hyperplastic primary vitreous". American Journal of Medical Genetics Part A. 140 (5): 503–8. doi:10.1002/ajmg.a.31085. PMID 16470791.
↑ "How are genetic conditions diagnosed?". United States Department of Health and Human Services. November 8, 2016. Missing or empty |url= (help)
1 2 "Axenfeld-Rieger syndrome type 1". National Center for Biotechnology Information.
↑ Tonoki, Hidefumi; Harada, Naoki; Shimokawa, Osamu; Yosozumi, Ayako; Monzaki, Kadomi; Satoh, Kohei; Kosaki, Rika; Sato, Atsushi; Matsumoto, Naomichi; Iizuka, Susumu (2011). "Axenfeld-Rieger anomaly and Axenfeld-Rieger syndrome: Clinical, molecular-cytogenetic, and DNA array analyses of three patients with chromosomal defects at 6p25". American Journal of Medical Genetics Part A. 155A (12): 2925–32. doi:10.1002/ajmg.a.33858. PMID 22009788.

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
"Rieger syndrome". National Center for Biotechnology Information.

Congenital malformations and deformations of eyes (Q10–Q15, 743)

Adnexa

Eyelid	Ptosis Ectropion Entropion Distichia Blepharophimosis Ablepharon Marcus Gunn phenomenon

Lacrimal apparatus	Congenital lacrimal duct obstruction

Globe

Entire eye	Anophthalmia (Cystic eyeball, Cryptophthalmos) Microphthalmia

Lens	Ectopia lentis Aphakia

Iris	Aniridia

Anterior segment	Axenfeld syndrome

Cornea	Keratoglobus Megalocornea

Other	Buphthalmos Coloboma (Coloboma of optic nerve) Hydrophthalmos Norrie disease

Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies

(1) Basic domains

1.2	Feingold syndrome Saethre–Chotzen syndrome

1.3	Tietz syndrome

(2) Zinc finger
DNA-binding domains

2.1	(Intracellular receptor): Thyroid hormone resistance Androgen insensitivity syndrome PAIS MAIS CAIS Kennedy's disease PHA1AD pseudohypoaldosteronism Estrogen insensitivity syndrome X-linked adrenal hypoplasia congenita MODY 1 Familial partial lipodystrophy 3 SF1 XY gonadal dysgenesis

2.2	Barakat syndrome Tricho–rhino–phalangeal syndrome

2.3	Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome Denys–Drash syndrome Duane-radial ray syndrome MODY 7 MRX 89 Townes–Brocks syndrome Acrocallosal syndrome Myotonic dystrophy 2

2.5	Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains

3.1	ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 Synpolydactyly PDX1 MODY 4 LMX1B Nail–patella syndrome MSX1 Tooth and nail syndrome OFC5 PITX2 Axenfeld syndrome 1 POU4F3 DFNA15 POU3F4 DFNX2 ZEB1 Posterior polymorphous corneal dystrophy Fuchs' dystrophy 3 ZEB2 Mowat–Wilson syndrome

3.2	PAX2 Papillorenal syndrome PAX3 Waardenburg syndrome 1&3 PAX4 MODY 9 PAX6 Gillespie syndrome Coloboma of optic nerve PAX8 Congenital hypothyroidism 2 PAX9 STHAG3

3.3	FOXC1 Axenfeld syndrome 3 Iridogoniodysgenesis, dominant type FOXC2 Lymphedema–distichiasis syndrome FOXE1 Bamforth–Lazarus syndrome FOXE3 Anterior segment mesenchymal dysgenesis FOXF1 ACD/MPV FOXI1 Enlarged vestibular aqueduct FOXL2 Premature ovarian failure 3 FOXP3 IPEX

3.5	IRF6 Van der Woude syndrome Popliteal pterygium syndrome

(4) β-Scaffold factors
with minor groove contacts

4.2	Hyperimmunoglobulin E syndrome

4.3	Holt–Oram syndrome Li–Fraumeni syndrome Ulnar–mammary syndrome

4.7	Campomelic dysplasia MODY 3 MODY 5 SF1 SRY XY gonadal dysgenesis Premature ovarian failure 7 SOX10 Waardenburg syndrome 4c Yemenite deaf-blind hypopigmentation syndrome

4.11	Cleidocranial dysostosis

(0) Other transcription factors

0.6	Kabuki syndrome

Ungrouped

Transcription coregulators

Coactivator:	CREBBP Rubinstein–Taybi syndrome

Corepressor:	HR (Atrichia with papular lesions)

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