Alternative titles; symbols
SNOMEDCT: 1674008; ICD10CM: H18.52; ICD9CM: 371.51; ORPHA: 98954; DO: 0080670;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q21.2 | Meesmann corneal dystrophy 1 | 122100 | Autosomal dominant | 3 | KRT12 | 601687 |
A number sign (#) is used with this entry because of evidence that Meesmann corneal dystrophy-1 (MECD1) is caused by heterozygous mutation in the KRT12 gene (601687) on chromosome 17q21.
Meesmann corneal dystrophy-1 (MECD1) is a dominantly inherited disorder characterized by the presence of multitudinous microcysts within the anterior epithelium on slit lamp examination. The disorder can cause foreign body sensation and photophobia but is often asymptomatic and detected in the course of routine eye examination. Microcysts are evident even in asymptomatic individuals. Rarely, a more severe phenotype with corneal erosions and scarring can lead to significant loss of visual acuity requiring treatment by keratoplasty or corneal grafting. A subtle feature is the presence of gray serpiginous lines within the anterior epithelium (summary by Liao et al., 2011).
Genetic Heterogeneity of Meesmann Corneal Dystrophy
MECD2 (618767) is caused by mutation in the KRT3 gene (148043) on chromosome 12q13.
Meesmann corneal epithelial dystrophy was originally described in Germany by Meesmann and Wilke (1939) and later documented by Stocker and Holt (1954, 1954) in descendants of German immigrants in the US. The condition usually appears in the first year or two of life, commencing with signs of irritation. The corneal changes, seen only with magnification, consist of myriads of fine punctate opacities in the epithelium and occasionally in Bowman membrane. Vision is only rarely impaired to a serious degree.
Behnke and Thiel (1965) demonstrated that all cases in Schleswig-Holstein were members of one kindred traced back to 1620. In the 4 living generations, 120 cases were demonstrated. Progression did not occur.
Alkemade and Van Balen (1966) observed 10 affected persons in 1 family. None had ocular complaints. Light microscopy shows a thickened basement membrane and electron microscopy shows a peculiar intracytoplasmic substance. Microcysts are filled with debris.
Badr et al. (1998) described the disorder in a Saudi Arabian family. The disorder was identified in 7 individuals, all but 1 of whom were 17 years of age or older. The findings were considered consistent with autosomal dominant inheritance with probable incomplete penetrance or delayed onset of phenotypic expression.
Liao et al. (2011) reported an extended, multigenerational British family with a severe form of autosomal dominant MECD. Affected persons tended to have recurrent corneal erosions with scarring leading to pain and reduced visual acuity. Slit-lamp photography revealed multiple microcysts in the anterior epithelium and also uneven corneal topography secondary to damage and scarring of the underlying basement membrane and anterior stroma. Several affected individuals in the family had been treated with corneal grafting, which is uncommon in MECD.
Chen et al. (2015) described an 8-year-old boy with Meesmann corneal dystrophy who had episodes of photophobia since age 1 year. His parents reported a negative family history of MECD or corneal transplantation. The boy's uncorrected visual acuity was 20/200-1 OD (pinhole 20/80) and 20/80 OS (pinhole no improvement). Slit-lamp examination revealed diffuse, bilateral punctate gray-white epithelial opacities. In the superior and inferior corneal quadrants, the epithelial opacities appeared in parallel lines that stained with fluorescein and extended to the limbus.
The transmission pattern of MECD1 in the families reported by Meesmann and Wilke (1939) (later by Irvine et al. (1997)), Stocker and Holt (1954, 1954), and Liao et al. (2011) was consistent with autosomal dominant inheritance. The family reported by Stocker and Holt (1954, 1954) had affected members in possibly 8 generations (4 generations were examined).
Patients with Meesmann corneal dystrophy are intolerant of contact lenses, as these devices directly traumatize the corneal epithelium (Irvine et al., 1997).
The intermediate filament cytoskeleton of corneal epithelial cells is composed of cornea-specific keratins KRT3 and KRT12. Because Meesmann corneal dystrophy causes fragility of the anterior corneal epithelium, where KRT3 and KRT12 are specifically expressed, Irvine et al. (1997) postulated that dominant-negative mutations in these keratins might be the cause of the disorder. In Meesmann's original German kindred, they obtained linkage to the KRT12 locus on 17q21 and found cosegregation with the KRT12 locus also in a pedigree in Northern Ireland. Linkage studies in a second pedigree in Northern Ireland showed cosegregation with the KRT3 locus on 12q13 (see MECD2, 618767).
In affected members of the original German kindred reported by Meesmann and Wilke (1939), Irvine et al. (1997) identified heterozygosity for a mutation in the KRT12 gene (601687.0001).
In affected members of a pedigree in Northern Ireland with MECD1, Irvine et al. (1997) identified heterozygosity for mutation in the KRT12 (601687.0002) gene. The mutation was not found in 100 normal unrelated chromosomes.
In all affected members of an extended, multigenerational British family with a severe form of autosomal dominant MECD, Liao et al. (2011) identified a heterozygous leu132-to-pro (L132P; 601687.0008) mutation in the KRT12 gene. The mutation was not found in 50 control individuals. Functional analyses showed that the L132P mutation was significantly more disruptive than the most common KRT12 mutation, arg135 to thr (R135T; 601687.0001), and resulted in greater keratin aggregate formation.
Alkemade, P. P. H., Van Balen, A. T. M. Hereditary epithelial dystrophy of the cornea. Brit. J. Ophthal. 50: 603-605, 1966. [PubMed: 5297150] [Full Text: https://doi.org/10.1136/bjo.50.10.603]
Badr, I. A., Basaffar, S., Jabak, M., Wagoner, M. D. Meesmann corneal epithelial dystrophy in a Saudi Arabian family. Am. J. Ophthal. 125: 182-186, 1998. [PubMed: 9467444] [Full Text: https://doi.org/10.1016/s0002-9394(99)80089-0]
Behnke, H., Thiel, H. J. Ueber die hereditaere Epitheldystrophie der Hornhaut (Typ Meesmann-Wilke) in Schleswig-Holstein. Klin. Monatsbl. Augenheilkd. 147: 662-672, 1965. [PubMed: 5296628]
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Chen, J. L., Lin, B. R., Gee, K. M., Gee, J. A., Chung, D.-W. D., Frausto, R. F., Deng, S. X., Aldave, A. J. Identification of presumed pathogenic KRT3 and KRT12 gene mutations associated with Meesmann corneal dystrophy. Molec. Vision 21: 1378-1386, 2015. [PubMed: 26788030]
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Irvine, A. D., Corden, L. D., Swensson, O., Swensson, B., Moore, J. E., Frazer, D. G., Smith, F. J. D., Knowlton, R. G., Christophers, E., Rochels, R., Uitto, J., McLean, W. H. I. Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's corneal dystrophy. Nature Genet. 16: 184-187, 1997. [PubMed: 9171831] [Full Text: https://doi.org/10.1038/ng0697-184]
Kuwabara, T., Ciccarelli, E. C. Meesmann's corneal dystrophy: a pathological study. Arch. Ophthal. 71: 672-682, 1964. [PubMed: 14120659] [Full Text: https://doi.org/10.1001/archopht.1964.00970010692015]
Liao, H., Irvine, A. D., Macewen, C. J., Weed, K. H., Porter, L., Corden, L. D., Gibson, A. B., Moore, J. E., Smith, F. J., McLean, W. H., Moore, C. B. Development of allele-specific therapeutic siRNA in Meesmann epithelial corneal dystrophy. PLoS One 6: e28582, 2011. Note: Electronic Article. [PubMed: 22174841] [Full Text: https://doi.org/10.1371/journal.pone.0028582]
Meesmann, A., Wilke, F. Klinische und anatomische Untersuchungen ueber eine bisher unbekannte, dominant vererbte Epitheldystrophie der Hornhaut. Klin. Monatsbl. Augenheilkd. 103: 361-391, 1939.
Snyder, W. B. Hereditary epithelial corneal dystrophy. Am. J. Ophthal. 55: 56-61, 1963. [PubMed: 13993171] [Full Text: https://doi.org/10.1016/0002-9394(63)91648-9]
Stocker, F. W., Holt, L. B. A rare form of hereditary epithelial dystrophy of the cornea: a genetic, clinical, and pathologic study. Trans. Am. Ophthal. Soc. 52: 133-144, 1954. [PubMed: 13274420]
Stocker, F. W., Holt, L. B. Rare form of hereditary epithelial dystrophy of the cornea: genetic, clinical, and pathologic study. AMA Arch. Ophthal. 53: 536-541, 1954. [PubMed: 14360886]