Cornea plana is clinically characterized by reduced corneal curvature leading in most cases to hyperopia, hazy corneal limbus, and arcus lipoides at an early age. An autosomal dominant form (CNA1; 121400) is mild, whereas an autosomal recessive form ... Cornea plana is clinically characterized by reduced corneal curvature leading in most cases to hyperopia, hazy corneal limbus, and arcus lipoides at an early age. An autosomal dominant form (CNA1; 121400) is mild, whereas an autosomal recessive form (CNA2) is severe and frequently associated with additional ocular manifestations (Tahvanainen et al., 1996).
Eriksson et al. (1973) pointed out that the autosomal recessive form has more severe manifestations than the dominant form (CNA1; 121400) in terms of reduced visual activity, extreme hyperopia (usually +10 diopters (D) or more), hazy corneal limbus, ... Eriksson et al. (1973) pointed out that the autosomal recessive form has more severe manifestations than the dominant form (CNA1; 121400) in terms of reduced visual activity, extreme hyperopia (usually +10 diopters (D) or more), hazy corneal limbus, opacities in the corneal parenchyma, and marked arcus senilis (often detected at an early age). Tahvanainen et al. (1996) noted that a round and opaque thickening, approximately 5 mm in width and located centrally, occurs in most cases of the recessive form but never in the dominant form. Additional anomalies such as malformations of the iris, a slit-like pupil, and adhesions between the iris and cornea are more prevalent in the recessive form. Tahvanainen et al. (1996) compared dominant and recessive forms of cornea plana in the Finnish population by measuring horizontal corneal refraction values in diopters. A control population of 473 individuals had a mean value of 43.4 (SD = 1.5 D) for men and 43.7 (SD = 1.6 D) for women, whereas in 51 subjects affected with CNA2, the mean value was 29.9 (SD = 5.1 D), and in 5 subjects affected with CNA1, the mean value was 37.8 (SD = 1.6 D).
Pellegata et al. (2000) cloned the human KERA gene as a candidate gene for CNA2 and identified mutations in 47 CNA2 patients. Forty-six Finnish patients were homozygous for a founder missense mutation leading to the substitution of a ... Pellegata et al. (2000) cloned the human KERA gene as a candidate gene for CNA2 and identified mutations in 47 CNA2 patients. Forty-six Finnish patients were homozygous for a founder missense mutation leading to the substitution of a highly conserved amino acid (603288.0001), and 1 Chinese American patient was homozygous for a mutation leading to a premature stop codon that truncates the KERA protein (603288.0002). In a consanguineous pedigree in which corneal plana cosegregated with microphthalmia, Lehmann et al. (2001) identified a homozygous thr215-to-lys substitution (603288.0003) at the start of a highly conserved leucine-rich repeat motif in keratocan. Structural modeling predicted that this mutation altered the length and position of 1 of these motifs on the beta-sheet array of keratocan. The authors concluded that normal corneal function is dependent on the regular spacing of collagen fibrils, and the predicted alteration of the tertiary structure of KERA is the probable mechanism of the cornea plana phenotype. Khan et al. (2004) described the ophthalmic phenotype of a family with autosomal recessive cornea plana due to a novel KERA mutation. Five of 6 sibs were affected and had small, flat corneas with arcus juvenilis and variable degrees of corneal clouding, variable anterior chamber depth, and severe hyperopia due to decreased axial length. Genetic testing revealed a novel homozygous nonsense mutation in exon 3 (603288.0004) of the keratocan gene in affected individuals. The clinically unaffected parents were confirmed as carriers; the clinically unaffected sib had no KERA mutation. The authors stated that this novel point mutation in the KERA gene was the fourth described to that time.