Axenfeld syndrome

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Axenfeld syndrome
Other namesAxenfeld-Rieger syndrome or Hagedoom syndrome
Axenfeld syndrome.jpg
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]
Specialty Medical genetics   OOjs UI icon edit-ltr-progressive.svg

Axenfeld syndrome is a rare autosomal dominant [2] disorder, which affects the development of the teeth, eyes, and abdominal region. [3]

Dominance (genetics) relationship between alleles of a gene, in which the phenotypic effect of one allele masks the phenotypic effect (phenotype) of another allele at the same locus

Dominance, in genetics, is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes (autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked, and these show a very different inheritance and presentation pattern to autosomal traits which depends on the sex of the individual. Additionally, there are other forms of dominance such as incomplete dominance, in which a gene variant has a partial effect compared to when it is present on both chromosomes, and co-dominance, in which different variants on each chromosome both show their associated traits.

Contents

Pathophysiology

Axenfeld syndrome has an autosomal dominant pattern of inheritance. Autosomal dominant - en.svg
Axenfeld syndrome has an autosomal dominant pattern of inheritance.

The molecular genetics of Axenfeld syndrome are poorly understood, but center on three genes identified by cloning of chromosomal breakpoints from patients. [5] [6]

Molecular genetics is the field of biology that studies the structure and function of genes at a molecular level and thus employs methods of both molecular biology and genetics. The study of chromosomes and gene expression of an organism can give insight into heredity, genetic variation, and mutations. This is useful in the study of developmental biology and in understanding and treating genetic diseases.

This disorder is inheritable as an autosomal dominant trait, [4] 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.[ citation needed ]

Autosome Any chromosome other than a sex chromosome.

An autosome is a chromosome that is not an allosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome pairs which may have different structures. The DNA in autosomes is collectively known as atDNA or auDNA.

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]

Glaucoma eye disease that is characterized by an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function

Glaucoma is a group of eye diseases which result in damage to the optic nerve and cause vision loss. The most common type is open-angle glaucoma with less common types including closed-angle glaucoma and normal-tension glaucoma. Open-angle glaucoma develops slowly over time and there is no pain. Peripheral vision may begin to decrease followed by central vision resulting in blindness if not treated. Closed-angle glaucoma can present gradually or suddenly. The sudden presentation may involve severe eye pain, blurred vision, mid-dilated pupil, redness of the eye, and nausea. Vision loss from glaucoma, once it has occurred, is permanent.

PITX2 protein-coding gene in the species Homo sapiens

Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.

The most characteristic feature affecting the eye is a distinct corneal posterior arcuate ring, known as an "embryotoxon". [8] The iris is commonly adherent to the Schwalbe's line (posterior surface of the cornea).[ citation needed ]

Schwalbes line

Schwalbe's line is the anatomical line found on the interior surface of the eye's cornea, and delineates the outer limit of the corneal endothelium layer. Specifically, it represents the termination of Descemet's membrane. In many cases it can be seen via gonioscopy.

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 have displayed mutations in genes PITX2, [7] FOXC1, and PAX6. [9] [10] The difference between Type 1, 2, and 3 Axenfeld Syndrome is the genetic cause, all three types display the same symptoms and abnormalities. [11]

Forkhead box C1 protein-coding gene in the species Homo sapiens

Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the FOXC1 gene.

PAX6 protein-coding gene in the species Homo sapiens

Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the PAX6 gene.

The OMIM classification is as follows:

Type OMIM Gene
Type 1 180500 PITX2
Type 2 601499 possibly FOXO1A [12]
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. [13] [ failed verification ]

Management

Eponym

It is named after the German ophthalmologist Theodor Axenfeld [14] [8] who studied anterior segment disorders, especially those such as Rieger Syndrome and the Axenfeld Anomaly.[ citation needed ]

Axenfeld-Rieger syndrome is characterized by abnormalities of the eyes, teeth, and facial structure. [11] 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. [12] The term "Rieger syndrome" is sometimes used to indicate an association with glaucoma. [7] Glaucoma occurs in up to 50% of patients with Rieger Syndrome. Glaucoma develops during adolescence or late childhood, but often occurs in infancy. [8] [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. [5] Below average height and stature, stunted development of the mid-facial features and mental deficiencies may also be observed in patients. [5]

See also

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References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. 1 2 "Axenfeld-Rieger syndrome type 1". National Center for Biotechnology Information.
  5. 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.
  6. ↑ 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.
  7. 1 2 3 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.
  8. 1 2 3 Axenfeld, T (1920). "Embryotoxon cornea posterius". Berichte der Deutschen Ophthalmologischen Gesellschaft. 42: 301–2.
  9. 1 2 3 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.
  10. ↑ Reis, LM; Semina, EV (September 2011). "Genetics of anterior segment dysgenesis disorders". Current Opinion in Ophthalmology. 22 (5): 314–24. doi:10.1097/ICU.0b013e328349412b. PMC   3558283 . PMID   21730847.
  11. 1 2 "Axenfeld-Rieger syndrome". United States Department of Health and Human Services. November 8, 2016.
  12. 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.
  13. ↑ "How are genetic conditions diagnosed?". United States Department of Health and Human Services. November 8, 2016.
  14. ↑ synd/1284 at Who Named It?

Further reading

Classification
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