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Lattice corneal dystrophy
Letters to the Editor
Lattice Corneal Dystrophy Dear Editor: Stewart et al1 have recently reported a new mutation (His626Arg) in the transforming growth factor -induced gene (ig-h3 gene) located on chromosome 5q31, linked to lattice corneal dystrophy (LCD). The affected individuals had an asymmetric, late-onset form of LCD, which was considered as a variant of type III-A. Interestingly, the phenotype displayed by these individuals was clearly heterogeneous, even within the two families described, concerning age at the onset of the disease, time of bilateral involvement, and occurrence of corneal epithelial breakdown. Contrasting with this heterogeneity, we found a strikingly homogeneous clinical expression in the members of a Caucasian family bearing this mutation [Schmitt-Bernard et al Invest Ophthalmol Vis Sci 1999;40(suppl.):468]. Eight members of a family with a history of LCD have been molecularly explored for mutations in the ig-h3 gene and clinically assessed or treated in our center since 1997. Three of the eight investigated individuals already had clinical signs of LCD at the first clinical examination. Affected members characteristically had a severe decrease of their visual acuity during the fourth decade of life, requiring corneal grafting in the fifth decade. They had no history of corneal erosions. Slit-lamp microscope examination showed subepithelial opaque, dense amyloid clumps and stromal thick lattice lines (Fig 1). Congo red staining of corneal
buttons displayed the characteristic red-green dichroism under polarized light, confirming the amyloid nature of the deposits. No multiorgan involvement was observed in any of the patients. The 58-year-old mother presented at the outpatient clinic with a bilateral dense corneal amyloid dystrophy leaving her best-corrected visual acuity as low as 20/400. Her 60-yearold sister had a clinically identical bilateral LCD. Both of them experienced dramatic reduction of visual acuity during the fourth decade of life. The initial slit-lamp examination of her 29-year-old son showed unilateral stellate amyloid deposits located in the lower center of his left cornea, which became bilateral the following year. Her two daughters (22 and 26 years old) did not display any clinically obvious corneal deposit at the first examination. One year later, the older daughter (aged 27), although asymptomatic, displayed stellate amyloid deposits initiating in the lower center of her left cornea. The younger one (23 years old) remained asymptomatic and had a normal clinical examination. Therefore, according to the clinical findings observed in the affected family members, the onset of the amyloid deposits can be situated at around 28 years of age. The deposits, first unilateral, are likely to become bilateral within the first years of the disease, and their progression leads to low visual acuity during the fourth decade of life. Recurrent corneal epithelial erosions did not occur in this family. Genetic screening identified the ig-h3 Hist626Arg mutation in all the affected family members. The phenotype of corneal amyloid dystrophy in this family was homogeneous and contrasted with those reported previously. The differences with types I and III-A were evident regarding all the clinical aspects of LCD: age of onset of the disease, age of severely reduced visual acuity, morphology of the subepithelial deposits, and occurrence of corneal erosions. Therefore, on the basis of the present observations and those reported by Stewart et al,1 the corneal disease associated with the single Hist626Arg mutation of the ig-h3 gene may be considered as a new type of clinically differentiated LCD, intermediate between type I and type III-A. Future reports of new families bearing this mutation will certainly shed more light on the clinical characterization of this new type of LCD. CLAIR-FLORENT SCHMITT-BERNARD, MD MIREILLE CLAUSTRES, MD, PHD BERNARD ARNAUD, MD JACQUES DEMAILLE, MD, PHD ` NGEL ARGILES, MD, PHD A Montpellier, France Reference
Figure 1. Slit-lamp microscopy. Corneal lattice dystrophy in the 58-yearold mother: stromal thick lattice lines (black arrow) and subepithelial clumps (white arrow) of amyloid deposits.
1. Stewart H, Black GC, Donnai D, et al. A mutation within exon 14 of the TGFBI (BIGH3) gene on chromosome 5q31 causes an asymmetric, late-onset form of lattice corneal dystrophy. Ophthalmology 1999;106:964 –70.
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Lattice Corneal Dystrophy Dear Editor: Stewart et al1 have recently reported a new mutation (His626Arg) in the transforming growth factor -induced gene (ig-h3 gene) located on chromosome 5q31, linked to lattice corneal dystrophy (LCD). The affected individuals had an asymmetric, late-onset form of LCD, which was considered as a variant of type III-A. Interestingly, the phenotype displayed by these individuals was clearly heterogeneous, even within the two families described, concerning age at the onset of the disease, time of bilateral involvement, and occurrence of corneal epithelial breakdown. Contrasting with this heterogeneity, we found a strikingly homogeneous clinical expression in the members of a Caucasian family bearing this mutation [Schmitt-Bernard et al Invest Ophthalmol Vis Sci 1999;40(suppl.):468]. Eight members of a family with a history of LCD have been molecularly explored for mutations in the ig-h3 gene and clinically assessed or treated in our center since 1997. Three of the eight investigated individuals already had clinical signs of LCD at the first clinical examination. Affected members characteristically had a severe decrease of their visual acuity during the fourth decade of life, requiring corneal grafting in the fifth decade. They had no history of corneal erosions. Slit-lamp microscope examination showed subepithelial opaque, dense amyloid clumps and stromal thick lattice lines (Fig 1). Congo red staining of corneal
buttons displayed the characteristic red-green dichroism under polarized light, confirming the amyloid nature of the deposits. No multiorgan involvement was observed in any of the patients. The 58-year-old mother presented at the outpatient clinic with a bilateral dense corneal amyloid dystrophy leaving her best-corrected visual acuity as low as 20/400. Her 60-yearold sister had a clinically identical bilateral LCD. Both of them experienced dramatic reduction of visual acuity during the fourth decade of life. The initial slit-lamp examination of her 29-year-old son showed unilateral stellate amyloid deposits located in the lower center of his left cornea, which became bilateral the following year. Her two daughters (22 and 26 years old) did not display any clinically obvious corneal deposit at the first examination. One year later, the older daughter (aged 27), although asymptomatic, displayed stellate amyloid deposits initiating in the lower center of her left cornea. The younger one (23 years old) remained asymptomatic and had a normal clinical examination. Therefore, according to the clinical findings observed in the affected family members, the onset of the amyloid deposits can be situated at around 28 years of age. The deposits, first unilateral, are likely to become bilateral within the first years of the disease, and their progression leads to low visual acuity during the fourth decade of life. Recurrent corneal epithelial erosions did not occur in this family. Genetic screening identified the ig-h3 Hist626Arg mutation in all the affected family members. The phenotype of corneal amyloid dystrophy in this family was homogeneous and contrasted with those reported previously. The differences with types I and III-A were evident regarding all the clinical aspects of LCD: age of onset of the disease, age of severely reduced visual acuity, morphology of the subepithelial deposits, and occurrence of corneal erosions. Therefore, on the basis of the present observations and those reported by Stewart et al,1 the corneal disease associated with the single Hist626Arg mutation of the ig-h3 gene may be considered as a new type of clinically differentiated LCD, intermediate between type I and type III-A. Future reports of new families bearing this mutation will certainly shed more light on the clinical characterization of this new type of LCD. CLAIR-FLORENT SCHMITT-BERNARD, MD MIREILLE CLAUSTRES, MD, PHD BERNARD ARNAUD, MD JACQUES DEMAILLE, MD, PHD ` NGEL ARGILES, MD, PHD A Montpellier, France Reference
Figure 1. Slit-lamp microscopy. Corneal lattice dystrophy in the 58-yearold mother: stromal thick lattice lines (black arrow) and subepithelial clumps (white arrow) of amyloid deposits.
1. Stewart H, Black GC, Donnai D, et al. A mutation within exon 14 of the TGFBI (BIGH3) gene on chromosome 5q31 causes an asymmetric, late-onset form of lattice corneal dystrophy. Ophthalmology 1999;106:964 –70.
1613