Ophthalmic and systemic findings of a family with Axenfeld-Rieger Anomaly

Objective & Hypothesis:Purpose: Axenfeld-Rieger Anomaly (ARA) is an autosomal dominant disorder of malformation of the anterior segment of the eye.

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Key Findings & Data:Methods: After getting history about 40 members of 5 generations, 17 subjected in last 3 generations were examined.

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Conclusion & Impact:The other subjects of families with affected members with ARA have to be evaluated systemically and ophthalmologically.

🔬Design:Research Article

📍Scope:Comprehensive Sample

⚙️Variables:Domain Parameters

Abstract

Purpose: Axenfeld-Rieger Anomaly (ARA) is an autosomal dominant disorder of malformation of the anterior segment of the eye. There are hetegenous clinical expressions. Different genetical defects have been reported from families with different origin. Systemic, genetic and ophthalmic features of members of a large pedigree, which was discovered from twin sisters whom diagnosed as ARA was evaluated in that study. Methods: After getting history about 40 members of 5 generations, 17 subjected in last 3 generations were examined. Blood samples were drawn from 15 subjects for DNA isolation and screened for PITX2, FOXC1 (FKHL7) and RIEG2 gene mutations. Results: ARA was affected 11 of family members and the glaucoma was diagnosed in 7 of them. Both probands underwent bilateral trabeculectomy and intraoperative Mitomycine C (MMC) application due insufficiency of topical antiglaucomatous medications. One of them underwent one-sided second trabeculectomy + MMC. Molecular genetic analyzes did not confirm genetic mutation of PITX2, FOXC1 (FHKL7) ve RIEG2 genes. Conclusion: Since none of the previously reported genes for ARA was found in that family there must be various responsible genetic mutations resulting in ARA. The other subjects of families with affected members with ARA have to be evaluated systemically and ophthalmologically.

Özet

Amaç: Bilateral gelişimsel ön kamara açı anomalilerinin bulunduğu Axenfeld-Rieger Anomalisi (ARA) genellikle otozomal dominant geçiş gösterir. Klinik bulgular bireyler arasında heterojen dağılır. Farklı ülkelerden bildirilen ailelerde farklı genetik defektler mevcuttur. Bu çalışmada ARA'lı tek yumurta ikizi kardeşlerin 40 bireyli ailelerinin oftalmik, sistemik ve genetik özellikleri incelendi. Yöntem: Probandlara ait 5 kuşak ile ilgili öykü elde edilip, 17 bireye detaylı oftalmolojik muayene uygulanmıştır. Bu olguların 15'inden periferik kan alınarak DNA'ları izole edilmiş PITX2, FOXC1 (FHKL7) ve RIEG2 gen içi mutasyonu taranmıştır. Bulgular: Aile ağacındaki bireylerden 11'inde ARA mevcut olup 7 olguda glokom saptanmıştır. Probandlara tıbbi tedavinin yetersiz kalması üzerine her iki gözlerine trabekülektomi ve intraoperatif Mitomisin C (MMC) uygulandı. Olgulardan birinde 4 yıl sonra bir gözüne ikinci kez trabekülektomi + MMC uygulandı. Aile bireylerinin moleküler analizinde PITX2, FOXC1 (FHKL7) ve RIEG2 geni içinde mutasyon gösterilememiştir. Sonuç: Otozomal dominant geçişin izlendiği bu ailede bilinen genetik lokuslara uyumlu genetik bir defektin bulunmaması ARA'sinde genetik çeşitliliği bir kez daha ortaya koymaktadır. ARA'lı olgular ve aile bireyleri göz ve sistemik tutulum yönünden incelenmeli ve tedavileri yönlendirilmelidir.

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Cite This Article

YALVAÇ, I., DUMAN, S., EKŞİOĞLU, Ü., MİDİLLİOĞLU, K. İ. (2022). Ophthalmic and systemic findings of a family with Axenfeld-Rieger Anomaly. Türk Oftalmoloji Dergisi, Cilt: 33 - Sayı: 4, 511–517. https://ajindex.com/articles/638965

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References (17)

Schields MB, Buckley E, Klintworth GK, Tresher R: Axenfeld-Rieger syndrome. A spectrum of developmental disorder. Surv Ophthalmol 1985;29:387-409
Riise R, Storhaug K, Brondum-Nielsen K: Rieger syndro- me is associated with PAX6 deletion. Acta Ophthalmol Scandinavica 2001; 79:201-3
Reese AB, Ellsworth RM: The anterior chamber cleavage syndrome. Arch Ophthalmol 1966;75:307-18
Özden S, Elyas H: Axenfeld-Rieger anomalisi. T Klin Oft 1993;3:302-6
Murray JC, Bennett SR, Kwitek AE, et al: Linkage of Ri- eger syndrome to the region of the epidermal growth fac- tor gene on chromosome 4. Nat Genet 1992,2:46-9
Heon E, Sheth BP, Kalenak JW, et al: Linkage of autoso- mal dominant iris hypoplasia to the Rieger syndrome lo- cus (4q25). Hum Mol Genet 1995;4:1435-9
Mears AJ, Jordan T, Mirzayans F, et al: Mutations of the forkhead/ winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly. Am J Hum Genet 1998;63:1316-28
Nishimura DY, Swiderski RE, Alward WLM, et al: The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6q25. Nat Genet 1998; 19:140-7
Perveen R, Lloyd IC, Clayton-SmithJ, et al: Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations. Invest Ophthalmol Vis Sci 2000;41:2456-60
Alward WLM, Semina EV, Kalenak JW, et al: Autosomal dominant iris hypoplasia is caused by a mutation in the Rieger syndrome (RIEG/PITX2) gene. Am J Opthtalmol 1998;125:98-100
Borges AS, Junior RS, Carani JCE et al: Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil. J Glaucoma 2002; 11:51-6
Koçak-Midillioğlu I, Karadeniz N, Yalvaç I, Koçak-Al- tıntaş AG, Duman S: Eight years follow-up of Axenfeld- Rieger syndrome with Turner syndrome. Euro J Ophthal- mol (basımda)
Philips JC, del Bono EA, Haines JL, et al: A second lokus for Rieger syndrome maps to chromosome 13ql4. Am J Hum Genet 1996;59:613-9
Caudill M, Barsoum-Homsy M, Chevrette L, Koçak I, Or M, Alper O, Lüleci G, Akarsu AN, Sarfarazi M: Mutation screening of the forkhead transcription factor FKHL7 in families with Axenfeld-Rieger Anomaly. Am J Hum Ge- net 1998:63;650
Turaçh ME, Aktan SG, Şaylı BS, Akarsu AN: Therapeu- tical and genetical aspects of congenital glaucomas. Int Ophthalmol 1992; 16:359-62
Sarfarazi M, Stoilov I: Molecular genetics of primary congenital glaucoma. Eye 2000; 14:422-8
Legius E, de Die Smulders CEM, Verbraak F, et al: Ge- netic