To present a small kindred with a unique dominantly inherited corneal stromal dystrophy.
A 31-year-old man was noted to have bilateral, symmetric, central discoid corneal stromal opacification. We performed bilateral penetrating keratoplasties for decreased visual acuity, glare, and photophobia.
Light microscopy revealed multiple extracellular vacuoles, concentrated in the anterior one-half of the central corneal stroma. Material within the vacuoles demonstrated intense reactivity with alcian blue and colloidal iron stains, consistent with glycosaminoglycan deposition. Transmission electron microscopy demonstrated nonmembrane-bound vacuoles in the stroma that contained a faintly osmiophilic matrix and black circular profiles. Immunohistochemical analysis of the vacuolar deposits revealed that chondroitin sulfate was the primary glycosaminoglycan present. A clinical and serologic evaluation revealed no evidence of a systemic storage disorder. Genetic analysis did not reveal a mutation in the coding region of the CHST6 gene.
Given these unique clinical and histopathologic findings as well as nearly identical clinical findings in the patient's father and one of four brothers, the authors believe that this represents a previously unreported, dominantly inherited corneal stromal dystrophy.
[Show abstract][Hide abstract] ABSTRACT: The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis.
The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis.
The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature.
This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available.
The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d.
[Show abstract][Hide abstract] ABSTRACT: To determine whether central discoid corneal dystrophy (CDCD), previously reported as a novel corneal dystrophy, is actually Schnyder corneal dystrophy (SCD) through screening of the UBIAD1 gene in the members of the family in which CDCD was reported.
Genetic analysis was performed in 3 affected members and 1 unaffected member of a pedigree with CDCD including the affected 31-year-old proband.
All 4 affected members of the described pedigree demonstrated discoid central corneal clouding, with subtle, superficial, crystalline deposits noted in one of the affected individuals. Screening of UBIAD1 in the affected individuals demonstrated a previously unreported missense mutation, p.Asp240Asn, which was not identified in an unaffected family member or in 100 control individuals.
The clinical findings of the family reported to have CDCD were indistinguishable from those found in SCD. However, CDCD was originally thought to be distinct from SCD because of the absence of positive lipid staining and the presence of alcian blue staining consistent with glycosaminoglycans in the proband's cornea. Our recent investigation has revealed that corneal specimens from other patients with SCD have also demonstrated staining for glycosaminoglycans. Discovery that mutations in UBIAD1 caused SCD allowed genetic testing of this CDCD family. Our newly reported UBIAD1 mutation suggests that CDCD is actually a variant of SCD. This report underscores the utility of genetic testing in determining whether newly described corneal dystrophies are in fact unique entities or just variants of well-known diseases.
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