Alternative titles; symbols
SNOMEDCT: 231930000; ORPHA: 98961; DO: 0060453;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q31.1 | Corneal dystrophy, Reis-Bucklers type | 608470 | Autosomal dominant | 3 | TGFBI | 601692 |
A number sign (#) is used with this entry because of evidence that Reis-Bucklers corneal dystrophy (CDRB, or CDB1) is caused by heterozygous mutation in the TGFBI gene (601692) on chromosome 5q31.
The TGFBI gene is mutant in several other forms of corneal dystrophy, including Thiel-Behnke corneal dystrophy (CDTB, or CDB2; 602082), lattice type I corneal dystrophy (CDL1; 122200), lattice type IIIA corneal dystrophy (CDL3A; 608471), Avellino corneal dystrophy (ACD; 607541), and Groenouw type I corneal dystrophy (CDGG1; 121900).
Reis-Bucklers corneal dystrophy (CDRB) is an autosomal dominant disorder of the superficial corneal stroma that manifests as recurrent corneal erosions in early childhood. Affected individuals develop corneal opacities that result in significant visual impairment. Microscopically, CDRB may be differentiated from other forms of corneal dystrophy by confluent opacities in the Bowman layer and subepithelium, which are the product of extracellular bodies that stain red with Masson trichrome stain and appear as crystalloid rod-shaped bodies on transmission electron microscopy (summary by Tanhehco et al., 2006).
Paufique and Bonnet (1966) described a family with members in 3 generations affected by Reis-Buckler corneal dystrophy. Most of the affected persons also had strabismus. The cornea presented a 'dusty' opacity and a rough map-like surface with a peripheral condensation ring separated from the limbus by a narrow strip of normal cornea. The lesions are primarily in Bowman membrane with secondary involvement of the epithelium and superficial part of the stroma. Relapsing corneal erosions occur between ages 8 and 20 and again in more severe form at about 40 or 50 years. The ultrastructure was described by Rice et al. (1968) and Akiya and Brown (1971). Almost every epithelial cell, but especially the basal cells, showed degenerative changes, i.e., swollen mitochondria, large vacuoles, swelling and disruption of the endoplasmic reticulum. Bowman membrane was almost completely replaced by masses of disoriented collagen fibrils and smaller electron-dense fibrils whose composition and origin have not been determined.
Moller (1989) concluded that Reis-Bucklers corneal dystrophy may be the same entity as Groenouw type I granular corneal dystrophy.
To clarify whether Thiel-Behnke corneal dystrophy is a separate entity from Reis-Bucklers corneal dystrophy, Kuchle et al. (1995) examined 28 corneal specimens with a clinically suspected diagnosis of corneal dystrophy of the Bowman layer by light and electron microscopy and reviewed the literature. Eight specimens came from patients with a honeycomb-shaped pattern of opacities at the level of the Bowman layer. Study of these 8 specimens disclosed destruction of Bowman layer, a subepithelial fibrocellular tissue with an undulant configuration, absence of the epithelial basement membrane in many areas, and the presence of 'curly' collagen fibers with a diameter of 9 to 15 nm. Kuchle et al. (1995) concluded that 2 distinct autosomal dominant CDBs exist and proposed the designation CDB type I (geographic or 'true' Reis-Bucklers dystrophy) and CDB type II (honeycomb-shaped or Thiel-Behnke dystrophy). Eight corneas were characterized as CDB type II. Visual loss is significantly greater in CDB I, and recurrences after keratoplasty or keratectomy seem to be earlier and more extensive in CDB I. Most cases previously reported as Reis-Bucklers dystrophy were thought by Kuchle et al. (1995) to be CDB II.
Kobayashi and Sugiyama (2007) used in vivo laser confocal microscopy to investigate microstructures in patients with genetically confirmed Thiel-Behnke or Reis-Bucklers corneal dystrophy. In the Thiel-Behnke type, the deposits in the epithelial basal cell layer showed homogeneous reflectivity with round edges accompanying dark shadows. In contrast, deposits in the Reis-Bucklers type in the same cell layer showed extremely high reflectivity from small granular materials without any shadows in all cases. In each dystrophy, the Bowman layer was replaced totally with pathologic materials; the reflectivity of those materials is much higher in the Reis-Bucklers type than in the Thiel-Behnke type.
The transmission pattern of Reis-Bucklers corneal dystrophy in the family reported by Paufique and Bonnet (1966) was consistent with autosomal dominant inheritance.
Dinh et al. (1999) reviewed 50 excimer laser phototherapeutic keratectomy (PTK) procedures. Preoperative diagnoses included Reis-Bucklers dystrophy, granular dystrophy, anterior basement membrane dystrophy (121820), lattice dystrophy, and Schnyder crystalline dystrophy (121800). The authors concluded that PTK can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies. Even though corneal dystrophies are likely to recur eventually after PTK, successful retreatment with PTK is possible.
In 6 families with various forms of corneal dystrophy, Munier et al. (1997) identified missense mutations in the TGFBI gene. All the mutations occurred at the CpG dinucleotide of 2 arginine codons: arg555 to trp (R555W; 601692.0001) in a family with CDGG1, arg555 to gln (R555Q; 601692.0002) in a family with CDTB, arg124 to cys (R124C; 601692.0003) in 2 families with CDL1, and arg124 to his (R124H; 601692.0004) in 2 families with ACD. The observations established a common molecular origin of several 5q31-linked corneal dystrophies. The family with CDTB was initially described as having Reis-Buckler corneal dystrophy, but in a later report (Munier et al., 2002) the phenotype was reclassified as CDTB.
Okada et al. (1998) described an arg124-to-leu mutation (R124L; 601692.0007) mutation in a 25-year-old man with progressive subepithelial geographic opacities of the cornea. This was thought to be an example of 'true' Reis-Bucklers corneal dystrophy with geographic opacities rather than honeycomb-shaped opacities (CDTB).
Kim et al. (2002) studied the molecular properties of wildtype and mutant BIGH3 proteins: specifically, the R124L (CDRB), R124C (CDL1), R124H (ACD), R555W (CDGG1), and R555Q (CDTB) mutations commonly found in 5q31-linked corneal dystrophies. They found that the mutations did not significantly affect the fibrillar structure, interactions with other extracellular matrix proteins, or adhesion activity in cultured corneal epithelial cells. In addition, the mutations apparently produced degradation products similar to those of wildtype BIGH3. BIGH3 polymerizes to form a fibrillar structure and strongly interacts with type I collagen (see 120150), laminin (see 150320), and fibronectin (135600).
Tanhehco et al. (2006) reported 2 unrelated cases of Reis-Bucklers corneal dystrophy caused by spontaneous mutations in the TGFBI gene. Both children had had multiple corneal erosions, and neither had a family history of corneal dystrophy. Analysis of the TGFBI gene identified the R124L mutation in both children. The mutation was not found in any of the parents.
Akiya, S., Brown, S. I. The ultrastructure of Reis-Bucklers' dystrophy. Am. J. Ophthal. 72: 549-554, 1971. [PubMed: 4105521] [Full Text: https://doi.org/10.1016/0002-9394(71)90851-8]
Bucklers, M. Ueber eine weitere familiaere Hornhautdystrophie (Reis). Klin. Monatsbl. Augenheilkd. 114: 386-397, 1949.
Dinh, R., Rapuano, C. J., Cohen, E. J., Laibson, P. R. Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy. Ophthalmology 106: 1490-1497, 1999. [PubMed: 10442892] [Full Text: https://doi.org/10.1016/S0161-6420(99)90441-4]
Hall, P. Reis-Bucklers dystrophy. Arch. Ophthal. 91: 170-173, 1974. [PubMed: 4592568] [Full Text: https://doi.org/10.1001/archopht.1974.03900060178002]
Kim, J-E., Park, R-W., Choi, J-Y., Bae, Y-C., Kim, K-S., Joo, C-K., Kim, I-S. Molecular properties of wild-type and mutant beta-IG-H3 proteins. Invest. Ophthal. Vis. Sci. 43: 656-661, 2002. [PubMed: 11867580]
Kobayashi, A., Sugiyama, K. In vivo laser confocal microscopy findings for Bowman's layer dystrophies (Thiel-Behnke and Reis-Bucklers corneal dystrophies). Ophthalmology 114: 69-75, 2007. [PubMed: 17198850] [Full Text: https://doi.org/10.1016/j.ophtha.2006.05.076]
Kuchle, M., Green, W. R., Volcker, H. E., Barraquer, J. Reevaluation of corneal dystrophies of Bowman's layer and the anterior stroma (Reis-Bucklers and Thiel-Behnke types): a light and electron microscopic study of eight corneas and a review of the literature. Cornea 14: 333-354, 1995. [PubMed: 7671605] [Full Text: https://doi.org/10.1097/00003226-199507000-00001]
Moller, H. U. Granular corneal dystrophy Groenouw type I (Grl) and Reis-Bucklers' corneal dystrophy (R-B): one entity? Acta Ophthal. 67: 678-684, 1989. [PubMed: 2694746] [Full Text: https://doi.org/10.1111/j.1755-3768.1989.tb04401.x]
Munier, F. L., Frueh, B. E., Othenin-Girard, P., Uffer, S., Cousin, P., Wang, M. X., Heon, E., Black, G. C. M., Blasi, M. A., Balestrazzi, E., Lorenz, B., Escoto, R., Barraquer, R., Hoeltzenbein, M., Gloor, B., Fossarello, M., Singh, A. D., Arsenijevic, Y., Zografos, L., Schorderet, D. F. BIGH3 mutation spectrum in corneal dystrophies. Invest. Ophthal. Vis. Sci. 43: 949-954, 2002. [PubMed: 11923233]
Munier, F. L., Korvatska, E., Djemai, A., Le Paslier, D., Zografos, L., Pescia, G., Schorderet, D. F. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nature Genet. 15: 247-251, 1997. [PubMed: 9054935] [Full Text: https://doi.org/10.1038/ng0397-247]
Okada, M., Yamamoto, S., Watanabe, H., Inoue, Y., Tsujikawa, M., Maeda, N., Shimomura, Y., Nishida, K., Kinoshita, S., Tano, Y. Granular corneal dystrophy with homozygous mutations in the kerato-epithelin gene. Am. J. Ophthal. 126: 169-176, 1998. [PubMed: 9727509] [Full Text: https://doi.org/10.1016/s0002-9394(98)00075-0]
Paufique, L., Bonnet, M. La dystrophie corneenne heredo-familiale de Reis-Bucklers. Ann. Ocul. (Paris) 199: 14-37, 1966. [PubMed: 5295360]
Rice, N. S. C., Ashton, N., Jay, B., Blach, R. K. Reis-Bucklers' dystrophy: a clinico-pathological study. Brit. J. Ophthal. 52: 577-603, 1968. [PubMed: 5303616] [Full Text: https://doi.org/10.1136/bjo.52.8.577]
Tanhehco, T. Y., Eifrig, D. E., Jr., Schwab, I. R., Rapuano, C. J., Klintworth, G. K. Two cases of Reis-Bucklers corneal dystrophy (granular corneal dystrophy type III) caused by spontaneous mutations in the TGFBI gene. Arch. Ophthal. 124: 589-593, 2006. [PubMed: 16606891] [Full Text: https://doi.org/10.1001/archopht.124.4.589]