Alternative titles; symbols
SNOMEDCT: 417065002; ORPHA: 98960; DO: 0060455;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q31.1 | Corneal dystrophy, Thiel-Behnke type | 602082 | Autosomal dominant | 3 | TGFBI | 601692 |
A number sign (#) is used with this entry because of evidence that Thiel-Behnke corneal dystrophy (CDTB) 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 Reis-Bucklers corneal dystrophy (CDRB, or CDB1; 608470), lattice type I corneal dystrophy (CDL1; 122200), lattice type IIIA corneal dystrophy (CDL3A; 608471), Avellino corneal dystrophy (ACD; 607541), Groenouw type I corneal dystrophy (CDGG1; 121900), and epithelial basement membrane corneal dystrophy (EBMD; 121820).
Thiel-Behnke corneal dystrophy (CDTB) is characterized by progressive honeycomb-like, subepithelial corneal opacities with recurrent erosions (Thiel and Behnke, 1967).
Thiel and Behnke (1967) described an autosomal dominant form of corneal dystrophy characterized by progressive honeycomb-like, subepithelial corneal opacities with recurrent erosions. They examined 74 members of a 4-generation family and identified 26 affected individuals.
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 CDTB in 3 families studied by Hou et al. (2012) 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 (121900), anterior basement membrane dystrophy (121820), lattice dystrophy (see 122200), 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.
Small et al. (1996) found linkage of Thiel-Behnke corneal dystrophy to markers on chromosome 5q in a single 5-generation family. They initially diagnosed the family as having Reis-Bucklers corneal dystrophy, but in a later report (Yee et al., 1997) stated that the finding of 'curly fibers' by electron microscopy was more consistent with a diagnosis of Thiel-Behnke corneal dystrophy. Multipoint analysis generated a maximum lod score of 4.25 between D5S414 and the IL9 gene (146931), which maps to 5q31.1. They pointed out that lattice type I, Avellino, and granular corneal dystrophies also map to the same region, suggesting that a corneal gene family exists in this region, or that these corneal dystrophies represent allelic heterogeneity, or that these are all the same disorder.
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.
Kim et al. (2002) studied the molecular properties of wildtype and mutant BIGH3 proteins: specifically, the arg124-to-leu (R124L; 601692.0007) (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). Mutations did not significantly affect these properties. Kim et al. (2002) concluded that mutant forms of BIGH3 might require other cornea-specific factors to form the abnormal accumulations seen in 5q31-linked corneal dystrophies.
Hou et al. (2012) identified an R555Q mutation (601692.0002) in the TGFBI gene in 6 affected members of 3 families (NTUH7, NTUH8, NTUH18) with corneal dystrophy of the Bowman layer with the characteristic honeycomb presentation of CDTB.
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]
Hou, Y.-C., Wang, I.-J., Hsiao, C.-H., Chen, W.-L., Hu, F.-R. Phenotype-genotype correlations in patients with TGFBI-linked corneal dystrophies in Taiwan. Molec. Vision 18: 362-371, 2012. [PubMed: 22355247]
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]
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]
Small, K. W., Mullen, L., Barletta, J., Graham, K., Glasgow, B., Stern, G., Yee, R. Mapping of Reis-Bucklers' corneal dystrophy to chromosome 5q. Am. J. Ophthal. 121: 384-390, 1996. [PubMed: 8604731] [Full Text: https://doi.org/10.1016/s0002-9394(14)70434-9]
Thiel, H.-J., Behnke, H. Eine bisher unbekannte subepitheliale hereditaere Hornhautdystrophie. Klin. Monatsbl. Augenheilkd. 150: 862-874, 1967. [PubMed: 5301630]
Yee, R. W., Sullivan, L. S., Lai, H. T., Stock, E. L., Lu, Y., Khan, M. N., Blanton, S. H., Daiger, S. P. Linkage mapping of Thiel-Behnke corneal dystrophy (CDB2) to chromosome 10q23-q24. Genomics 46: 152-154, 1997. [PubMed: 9403072] [Full Text: https://doi.org/10.1006/geno.1997.5028]