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Rieger anomaly(RIEG)

MedGen UID:
78558
Concept ID:
C0265341
Disease or Syndrome
Synonyms: Goniodysgenesis hypodontia; Iridogoniodysgenesis with somatic anomalies; RIEG
SNOMED CT: Rieger's syndrome (47507006); Rieger anomaly (47507006); Rieger syndrome (47507006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related genes: PITX2, FOXC1
 
HPO: HP:0000558
Monarch Initiative: MONDO:0019628
Orphanet: ORPHA91483

Definition

Axenfeld-Rieger syndrome is primarily an eye disorder, although it can also affect other parts of the body. This condition is characterized by abnormalities of the front part of the eye, an area known as the anterior segment. For example, the colored part of the eye (the iris), may be thin or poorly developed. The iris normally has a single central hole, called the pupil, through which light enters the eye. People with Axenfeld-Rieger syndrome often have a pupil that is off-center (corectopia) or extra holes in the iris that can look like multiple pupils (polycoria). This condition can also cause abnormalities of the cornea, which is the clear front covering of the eye.

About half of affected individuals develop glaucoma, a serious condition that increases pressure inside the eye. When glaucoma occurs with Axenfeld-Rieger syndrome, it most often develops in late childhood or adolescence, although it can occur as early as infancy. Glaucoma can cause vision loss or blindness.

The signs and symptoms of Axenfeld-Rieger syndrome can also affect other parts of the body. Many affected individuals have distinctive facial features such as widely spaced eyes (hypertelorism); a flattened mid-face with a broad, flat nasal bridge; and a prominent forehead. The condition is also associated with dental abnormalities including unusually small teeth (microdontia) or fewer than normal teeth (oligodontia). Some people with Axenfeld-Rieger syndrome have extra folds of skin around their belly button (redundant periumbilical skin). Other, less common features can include heart defects, the opening of the urethra on the underside of the penis (hypospadias), narrowing of the anus (anal stenosis), and abnormalities of the pituitary gland that can result in slow growth.

Researchers have described at least three types of Axenfeld-Rieger syndrome. The types, which are numbered 1 through 3, are distinguished by their genetic cause. [from MedlinePlus Genetics]

Conditions with this feature

Irido-corneo-trabecular dysgenesis
MedGen UID:
91031
Concept ID:
C0344559
Congenital Abnormality
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Patients with ASGD5 have been reported with the Peters anomaly, Axenfeld anomaly, and Rieger anomaly subtypes. Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (Peters, 1906). It occurs as an isolated ocular abnormality or in association with other ocular defects. In Axenfeld anomaly, strands of iris tissue attach to the Schwalbe line; in Rieger anomaly, in addition to the attachment of iris tissue to the Schwalbe line, there is clinically evident iris stromal atrophy with hole or pseudo-hole formation and corectopia (summary by Smith and Traboulsi, 2012).
SHORT syndrome
MedGen UID:
164212
Concept ID:
C0878684
Disease or Syndrome
SHORT syndrome is a mnemonic for short stature, hyperextensibility, ocular depression (deeply set eyes), Rieger anomaly, and teething delay. It is now recognized that the features most consistently observed in SHORT syndrome are mild intrauterine growth restriction (IUGR); mild to moderate short stature; partial lipodystrophy (evident in the face, and later in the chest and upper extremities, often sparing the buttocks and legs); and a characteristic facial gestalt. Insulin resistance may be evident in mid-childhood or adolescence, although diabetes mellitus typically does not develop until early adulthood. Other frequent features include Axenfeld-Rieger anomaly or related ocular anterior chamber dysgenesis, delayed dentition and other dental issues, and sensorineural hearing loss.
Pierson syndrome
MedGen UID:
373199
Concept ID:
C1836876
Disease or Syndrome
Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).
Growth delay due to insulin-like growth factor I resistance
MedGen UID:
338622
Concept ID:
C1849157
Disease or Syndrome
Patients with mutations in the receptor for insulin-like growth factor I show intrauterine growth retardation and postnatal growth failure, resulting in short stature and microcephaly. Other features may include delayed bone age, developmental delay, and dysmorphic features.
Axenfeld-Rieger anomaly with partially absent eye muscles, distinctive face, hydrocephaly, and skeletal abnormalities
MedGen UID:
349489
Concept ID:
C1862373
Disease or Syndrome
Anterior segment dysgenesis 3
MedGen UID:
355748
Concept ID:
C1866560
Disease or Syndrome
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Some patients with ASGD3 have been reported with the following subtypes: iridogoniodysgenesis, Peters anomaly, Axenfeld anomaly, and Rieger anomaly. Iridogoniodysgenesis, which is characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma, is the result of aberrant migration or terminal induction of the neural crest cells involved in the formation of the anterior segment of the eye (summary by Mears et al., 1996). Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (Peters, 1906). In Axenfeld anomaly, strands of iris tissue attach to the Schwalbe line; in Rieger anomaly, in addition to the attachment of iris tissue to the Schwalbe line, there is clinically evident iris stromal atrophy with hole or pseudo-hole formation and corectopia (summary by Smith and Traboulsi, 2012).
4p partial monosomy syndrome
MedGen UID:
408255
Concept ID:
C1956097
Disease or Syndrome
Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (Battaglia et al., 2008).
Axenfeld-Rieger syndrome type 1
MedGen UID:
811487
Concept ID:
C3714873
Disease or Syndrome
Axenfeld-Rieger syndrome is an autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals (Fitch and Kaback, 1978). Systemic anomalies are associated, including dental hypoplasia, failure of involution of periumbilical skin, and maxillary hypoplasia (Alkemade, 1969). Genetic Heterogeneity of Axenfeld-Rieger Syndrome Linkage studies indicate that a second type of Axenfeld-Rieger syndrome maps to chromosome 13q14 (RIEG2; 601499). A third form of Axenfeld-Rieger syndrome (RIEG3; 602482) is caused by mutation in the FOXC1 gene (601090) on chromosome 6p25. See 109120 for a form of Axenfeld-Rieger syndrome associated with partially absent eye muscles, hydrocephalus, and skeletal abnormalities.

Professional guidelines

PubMed

Zhou L, Wang X, An J, Zhang Y, He M, Tang L
Exp Eye Res 2023 Jan;226:109307. Epub 2022 Nov 25 doi: 10.1016/j.exer.2022.109307. PMID: 36442680
Holtz AM, VanCoillie R, Vansickle EA, Carere DA, Withrow K, Torti E, Juusola J, Millan F, Person R, Guillen Sacoto MJ, Si Y, Wentzensen IM, Pugh J, Vasileiou G, Rieger M, Reis A, Argilli E, Sherr EH, Aldinger KA, Dobyns WB, Brunet T, Hoefele J, Wagner M, Haber B, Kotzaeridou U, Keren B, Heron D, Mignot C, Heide S, Courtin T, Buratti J, Murugasen S, Donald KA, O'Heir E, Moody S, Kim KH, Burton BK, Yoon G, Campo MD, Masser-Frye D, Kozenko M, Parkinson C, Sell SL, Gordon PL, Prokop JW, Karaa A, Bupp C, Raby BA
Genet Med 2022 Oct;24(10):2065-2078. Epub 2022 Aug 18 doi: 10.1016/j.gim.2022.07.005. PMID: 35980381Free PMC Article
Ma AS, Grigg JR, Jamieson RV
Hum Genet 2019 Sep;138(8-9):899-915. Epub 2018 Sep 21 doi: 10.1007/s00439-018-1935-7. PMID: 30242500

Recent clinical studies

Etiology

Achanta DSR, Chaurasia S, Mohamed A, Barur SR, Ramappa M, Edward DP
Cornea 2023 Oct 1;42(10):1216-1220. Epub 2022 Oct 17 doi: 10.1097/ICO.0000000000003163. PMID: 36255854
Karaconji T, Zagora S, Grigg JR
Clin Exp Ophthalmol 2022 Mar;50(2):232-246. Epub 2022 Jan 25 doi: 10.1111/ceo.14039. PMID: 35023613
Mandal AK, Pehere N
Eye (Lond) 2016 Jul;30(7):936-42. Epub 2016 Apr 8 doi: 10.1038/eye.2016.66. PMID: 27055677Free PMC Article
Amendt BA, Semina EV, Alward WL
Cell Mol Life Sci 2000 Oct;57(11):1652-66. doi: 10.1007/pl00000647. PMID: 11092457
Alward WL
Am J Ophthalmol 2000 Jul;130(1):107-15. doi: 10.1016/s0002-9394(00)00525-0. PMID: 11004268

Diagnosis

Reis LM, Amor DJ, Haddad RA, Nowak CB, Keppler-Noreuil KM, Chisholm SA, Semina EV
Genes (Basel) 2023 Oct 17;14(10) doi: 10.3390/genes14101948. PMID: 37895297Free PMC Article
Shakrawal J, Bhatnagar KR, Agarwal N
J Fr Ophtalmol 2023 Sep;46(7):829-830. Epub 2023 May 22 doi: 10.1016/j.jfo.2022.12.033. PMID: 37225607
Reis LM, Maheshwari M, Capasso J, Atilla H, Dudakova L, Thompson S, Zitano L, Lay-Son G, Lowry RB, Black J, Lee J, Shue A, Kremlikova Pourova R, Vaneckova M, Skalicka P, Jedlickova J, Trkova M, Williams B, Richard G, Bachman K, Seeley AH, Costakos D, Glaser TM, Levin AV, Liskova P, Murray JC, Semina EV
J Med Genet 2023 Apr;60(4):368-379. Epub 2022 Jul 26 doi: 10.1136/jmg-2022-108646. PMID: 35882526Free PMC Article
Karaconji T, Zagora S, Grigg JR
Clin Exp Ophthalmol 2022 Mar;50(2):232-246. Epub 2022 Jan 25 doi: 10.1111/ceo.14039. PMID: 35023613
Eldib A, Janczewski S, Nischal KK
Dev Ophthalmol 2021;61:40-45. Epub 2021 Feb 16 doi: 10.1159/000511816. PMID: 33592614

Therapy

Kumar P, Senthil S
J Glaucoma 2019 Aug;28(8):e136-e139. doi: 10.1097/IJG.0000000000001283. PMID: 31135590
Atkinson CS, Brodsky MC, Hiles DA, Simon JW
J Pediatr Ophthalmol Strabismus 1994 Nov-Dec;31(6):387-90. doi: 10.3928/0191-3913-19941101-09. PMID: 7714703

Prognosis

Nastasi S, Gonzalez A, Blake CR, Beck A, Agarwal-Sinha S
J Glaucoma 2018 Oct;27(10):e165-e167. doi: 10.1097/IJG.0000000000001046. PMID: 30095606
Mandal AK, Pehere N
Eye (Lond) 2016 Jul;30(7):936-42. Epub 2016 Apr 8 doi: 10.1038/eye.2016.66. PMID: 27055677Free PMC Article
Mortemousque B, Amati-Bonneau P, Couture F, Graffan R, Dubois S, Colin J, Bonneau D, Morissette J, Lacombe D, Raymond V
Arch Ophthalmol 2004 Oct;122(10):1527-33. doi: 10.1001/archopht.122.10.1527. PMID: 15477465
Komatireddy S, Chakrabarti S, Mandal AK, Reddy AB, Sampath S, Panicker SG, Balasubramanian D
Mol Vis 2003 Feb 18;9:43-8. PMID: 12592227
Panicker SG, Sampath S, Mandal AK, Reddy AB, Ahmed N, Hasnain SE
Invest Ophthalmol Vis Sci 2002 Dec;43(12):3613-6. PMID: 12454026

Clinical prediction guides

Gołaszewska K, Dub N, Saeed E, Mariak Z, Konopińska J
BMC Ophthalmol 2021 Mar 29;21(1):154. doi: 10.1186/s12886-021-01899-2. PMID: 33781219Free PMC Article
Espinosa-Barberi G, Galván González JF, Antón A
Rom J Ophthalmol 2020 Oct-Dec;64(4):455-458. doi: 10.22336/rjo.2020.70. PMID: 33367186Free PMC Article
Thauvin-Robinet C, Auclair M, Duplomb L, Caron-Debarle M, Avila M, St-Onge J, Le Merrer M, Le Luyer B, Héron D, Mathieu-Dramard M, Bitoun P, Petit JM, Odent S, Amiel J, Picot D, Carmignac V, Thevenon J, Callier P, Laville M, Reznik Y, Fagour C, Nunes ML, Capeau J, Lascols O, Huet F, Faivre L, Vigouroux C, Rivière JB
Am J Hum Genet 2013 Jul 11;93(1):141-9. Epub 2013 Jun 27 doi: 10.1016/j.ajhg.2013.05.019. PMID: 23810378Free PMC Article
Reis LM, Tyler RC, Volkmann Kloss BA, Schilter KF, Levin AV, Lowry RB, Zwijnenburg PJ, Stroh E, Broeckel U, Murray JC, Semina EV
Eur J Hum Genet 2012 Dec;20(12):1224-33. Epub 2012 May 9 doi: 10.1038/ejhg.2012.80. PMID: 22569110Free PMC Article
Kniestedt C, Taralczak M, Thiel MA, Stuermer J, Baumer A, Gloor BP
Ophthalmology 2006 Oct;113(10):1791.e1-8. Epub 2006 Jul 31 doi: 10.1016/j.ophtha.2006.05.017. PMID: 16876867

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