Corneal Dystrophy, Lattice Type I

A number sign (#) is used with this entry because of evidence that lattice corneal dystrophy type I (LCD1) is caused by heterozygous mutation in the gene encoding keratoepithelin (TGFBI; 601692) on chromosome 5q31.

Heterozygous mutation in the TGFBI gene causes several other forms of autosomal dominant corneal dystrophy.

Clinical Features

Frayer and Blodi (1959) described a family. Grayish lines like cotton threads are mainly limited to a zone between the center of the cornea and the periphery, usually not extending to the limbus. Rounded dots with distinct borders are scattered everywhere. The cornea between opacities is relatively clear. Visual activity is usually normal in childhood. In this and the granular type, the histologic findings are hyaline degeneration and absence of acid mucopolysaccharide deposition. The changes involve particularly the central portion of the cornea, becoming evident in adolescence and consisting of delicate, double-contoured, interdigitating, elongated deposits that form a reticular pattern in the corneal stroma. Recurrent corneal ulceration sometimes occurs. Progression to severe visual impairment by the fifth or sixth decade is the rule. No signs of systemic abnormality have been described.

Klintworth (1967) presented evidence that corneal dystrophy of the lattice type is a local variety of amyloidosis. Lattice corneal dystrophy accompanied systemic amyloidosis of the Finnish type (105120).

Meretoja (1973) suggested the existence of 2 and perhaps 3 distinct forms of lattice corneal dystrophy without systemic abnormality. In type I, manifestation is early, i.e., in the first or second decade. In type II, manifestation is later with reasonably good visual acuity retained until age 50 to 70. The lattice lines in type II are thicker and fewer, leaving portions of the central cornea clear, with few or no spots or crystals. Patients have fewer erosions. Type III, of more questionable distinctness, is illustrated by the case of Wolter and Henderson (1963). Waring et al. (1978) and Gorevic et al. (1984) distinguished 3 inherited forms of lattice corneal dystrophy on clinical and histologic grounds: type I, the autosomal dominant form discussed here, which is not associated with systemic amyloidosis; type II, which is associated with systemic amyloidosis (the Finnish type); and type III, the recessive form, which has an onset at age 70 to 90 years and is not associated with systemic amyloidosis (the Japanese type; 204870).

The Meretoja form of lattice corneal dystrophy is part of the Finnish form of amyloidosis and is due to a specific mutation in the gelsolin gene (137350.0001). In a large multigeneration Manitoba kindred of Belgian descent, Wiens et al. (1992) demonstrated that the gene causing autosomal dominant lattice corneal dystrophy without systemic amyloidosis was not linked to the gelsolin gene.

Clinical Management

Dinh et al. (1999) reviewed 50 excimer laser phototherapeutic keratectomy (PTK) procedures. Preoperative diagnoses included Reis-Bucklers dystrophy (see 121900), granular dystrophy (121900), 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 re-treatment with PTK is possible.

Mapping

Stone et al. (1994) found that the gene for lattice corneal dystrophy type I maps to 5q, in the same region as the gene for granular corneal dystrophy Groenouw type I (CDGG1; 121900) and the atypical combined granular/lattice corneal dystrophy known as the Avellino form (ACD; 607541).

Molecular Genetics

Munier et al. (1997) established that mutation of the gene encoding keratoepithelin (601692.0003) can cause LCD1. They postulated that the mutation resulted in amyloidogenic intermediates.

Kim et al. (2002) studied the molecular properties of wildtype and mutant TGFBI proteins: specifically, the arg124-to-leu (R124L; 601692.0007) (Reis-Bucklers corneal dystrophy (CDRB; 608470)), arg124-to-cys (R124C; 601692.0003) (LCD1), arg124-to-his (R124H; 601692.0004) (ACD), arg555-to-trp (R555W; 601692.0001) (CDGG1), and arg555-to-gln (R555Q; 601692.0002) (Thiel-Behnke corneal dystrophy (CDTB; 602082)) 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 TGFBI. TGFBI 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 TGFBI might require other cornea-specific factors to form the abnormal accumulations seen in 5q31-linked corneal dystrophies.

In an extensively studied African American family with lattice corneal dystrophy, Klintworth et al. (2004) and Aldave et al. (2004) reported 2 heterozygous mutations in the TGFBI gene (ala546 to asp and pro551 to gln; 601692.0009).