gene: UBIAD1
Only 50% of affected patients have corneal crystals. The severity of dyslipidemia does not directly correlate with the amount of corneal lipid deposition (PMID:21540632).
Schnyder corneal dystrophy (SCCD), also known as Schnyder crystalline corneal dystrophy, is an autosomal dominant eye disease characterized by abnormal deposition of cholesterol and phospholipids in the cornea. The consequent corneal opacification is progressive and bilateral, resulting in ... Schnyder corneal dystrophy (SCCD), also known as Schnyder crystalline corneal dystrophy, is an autosomal dominant eye disease characterized by abnormal deposition of cholesterol and phospholipids in the cornea. The consequent corneal opacification is progressive and bilateral, resulting in glare and loss of vision that is postulated to be caused by light scattering. Patients demonstrate a characteristic pattern of corneal opacification dependent on age, and only half have crystalline corneal cholesterol deposits. Patients with noncrystalline disease have a more subtle presentation with only corneal haze, which may be difficult to diagnose (summary by Nickerson et al., 2013).
Schnyder corneal dystrophy, which begins early in life, presents as an oval or annular clouding of the central part of the cornea with the periphery remaining clear. Involvement extends toward the limbus but usually leaves a clear peripheral ... Schnyder corneal dystrophy, which begins early in life, presents as an oval or annular clouding of the central part of the cornea with the periphery remaining clear. Involvement extends toward the limbus but usually leaves a clear peripheral area. Corneal sensitivity is normal. Slit-lamp examination shows in the opacified area many small iridescent needle-shaped shiny crystals of unknown composition. The opacity is located in the anterior portion of the stroma just posterior to Bowman membrane. The epithelium is normal. Gillespie and Covelli (1963) reported father-to-son transmission. The cornea has the appearance of crystalline dystrophy in cystinosis. Malbran et al. (1953) described a family. Luxenberg (1967) gave further information on members of a family reported by Fry and Pickett (1950). Clouding may be congenital but progresses little. The lesions are bilateral, centrally located and irregular in outline. Deposits occur in the anterior stroma near Bowman membrane and extend irregularly into deeper layers. Delleman and Winkelman (1968) described 2 families. In 1 family, 21 persons in 6 generations were affected and genu valgum was rather consistently associated. By histochemistry and electron microscopy, the crystals were shown to be cholesterol (Garner and Tripathi, 1972). Lisch et al. (1986) examined 13 affected members of 2 unrelated families with SCCD, 8 of whom had previously been examined in 1975 and 1976. The corneal alterations were bilateral and symmetric in all patients. An exclusively crystalline form of corneal opacification was seen in 2 patients, an exclusively diffuse form in 4 patients, and a combined form in 7 patients. The corneal opacities never regressed, and progression was more frequent in diffuse than in crystalline opacities. Both crystalline and diffuse opacities reappeared and progressed following penetrating keratoplasty. Mean cholesterol levels in affected individuals were above normal and 6 patients had moderate IIa dyslipoproteinemia (see 143890), but 2 patients had low apoB (107730). The degree of corneal opacification showed no relationship to dyslipoproteinemia. Lisch et al. (1986) concluded that Schnyder corneal dystrophy involves the corneal lipid metabolism only and is not a systemic disease. From quantitative biochemical analysis performed on a corneal button obtained from a patient with clinically and pathologically proven Schnyder dystrophy, McCarthy et al. (1994) concluded that phospholipid, unesterified cholesterol and cholesterol ester are the predominant lipids. They suggested that this is a primary disorder of corneal lipid metabolism. Battisti et al. (1998) described a family in which SCCD was transmitted through 4 generations with, however, no instance of male-to-male transmission. The propositus and his mother had genu valgum in addition to the corneal dystrophy. The propositus also had mental retardation and mild cerebellar hypoplasia. The neurologic impairment was considered coincidental. Results of serum lipid analysis were normal in all patients. Ultrastructural study of a skin biopsy specimen and fibroblast pellet showed membrane-bound spherical vacuoles containing lipid material. Cultured fibroblasts stained with filipin, a fluorescent probe that specifically binds unesterified cholesterol, showed abnormal cytoplasmic fluorescent material, suggesting an abnormality of cholesterol metabolism. Nickerson et al. (2013) studied 4 large 6-generation Finnish SCCD families with a common surname, who had ancestry from towns located within 60 miles of each other and shared a common haplotype of chromosome 1p36 microsatellite markers and SNPs extending across the UBIAD1 locus, indicating a high probability that disease in these families occurred due to a founder mutation. Examination of affected individuals revealed that virtually all exhibited characteristic age-dependent corneal changes. Within each family, however, there were individuals with significant differences in clinical manifestation of disease: corneal crystals were found in some but not all affected members, and crystals were observed in only one eye of some patients. Thus, individuals with acrystalline and crystalline forms of disease were present within a family, suggesting that differences in disease phenotype might be due to additional unknown genetic or environmental factors. Nickerson et al. (2013) noted that review of family photographs from the late 1800s showed affected individuals and documented occurrence of the disease 3 decades before the seminal description of SCCD by Van Went and Wibaut (1924).
Orr et al. (2007) analyzed 9 candidate genes in 5 families with SCCD, including 2 families previously reported by McCarthy et al. (1994) and Battisti et al. (1998), respectively, and identified 5 different heterozygous missense mutations in the ... Orr et al. (2007) analyzed 9 candidate genes in 5 families with SCCD, including 2 families previously reported by McCarthy et al. (1994) and Battisti et al. (1998), respectively, and identified 5 different heterozygous missense mutations in the UBIAD1 gene (see 611632.0001 and 611632.0003-611632.0006, respectively). By DNA sequencing of the UBIAD1 gene in 6 families segregating SCCD, Weiss et al. (2007) identified heterozygous mutations in the UBAID1 gene (611632.0001-611632.0002). Weiss et al. (2008) analyzed the UBIAD1 gene in 30 affected and 6 unaffected members of 14 families with SCCD, including pedigrees 'I' and 'II' previously described by Lisch et al. (1986) and pedigrees '8' and '10' studied by Theendakara et al. (2004), and identified heterozygous missense mutations in all affected members (see, e.g. 611632.0001, 611632.0002, 611632.0004, 611632.0007-611632.0009). In 47 affected individuals from 4 large 6-generation Finnish families, a 3-generation Japanese family, and a 4-generation Turkish family, all segregating autosomal dominant SCCD, Nickerson et al. (2013) identified heterozygosity for a missense mutation in the UBIAD1 gene (G177E; 611632.0010).