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Report of a New Family with Dominant Congenital Heredity Stromal Dystrophy of the Cornea

Van Ginderdeuren, Rita M.D.; De Vos, Rita Ph.D.; Casteels, Ingele M.D., Ph.D.; Foets, Bea M.D., Ph.D.

Case Reports
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Purpose. To report a new family with the rare form of congenital and hereditary stromal dystrophy of the cornea.

Methods. A mother and son, showing a bilateral congenital clouding of the cornea, were studied clinically and by biomicroscopy. After corneal transplantation, light microscopy and electron microscopy were performed.

Results. The stroma of the cornea was bilaterally and symmetrically thickened with diffuse and homogeneous small opacities. The opacities were present at birth and slowly progressive. Visual acuity was reduced to 2/10. Electron microscopy of the excised corneas showed a thickened stroma owing to cleaving of the lamellae by alternating layers of small-diameter collagen fibrils arranged in a random fashion. The epithelium, Bowman's membrane, the endothelium, and Descemet's membrane were normal.

Conclusions. This family presents with a congenital stromal dystrophy of the cornea not linked to endothelial defects and thus differs from the more common form of congenital hereditary corneal endothelial dystrophy.

From the Departments of Ophthalmology (R.V.G., I.C., B.F.) and Pathology (R.D.V.), UZ Leuven, Belgium.

Submitted March 31, 2001.

Revision received September 10, 2001.

Accepted September 11, 2001.

Address correspondence and reprint requests to Dr. R. Van Ginderdeuren, Dept. Oogziekten, UZ Leuven, Kapucijnenvoer 33, B 3000 Leuven, Belgium. E-mail: Rita.Vanginderdeuren@uz.kuleuven.ac.be

Bilateral congenital opacifications of the cornea can be related to congenital glaucoma, malformation of the anterior segment, inflammation, systemic storage disease, or dystrophy. 1,2 Congenital dystrophy of the cornea has been linked in most cases to an endothelial dysfunction with stromal edema as the presenting sign and fits into the category of congenital hereditary endothelial dystrophy or posterior polymorphous dystrophy. 1,2 Another very rare hereditary dystrophy with presentation at childhood is the posterior amorphous corneal dystrophy, which consists of changes in the posterior stroma and Descemet's layer and loss of endothelial cells. 3,4

Only two pedigrees are known with a different form of congenital dystrophy, which is not linked to the endothelium but is a result of disordered stromal fibrogenesis; this disorder is termed congenital hereditary stromal dystrophy of the cornea, and the inheritance is autosomal dominant. A very large French family with an American branch and a different unrelated American family were described in 1978 5 and in 1979, 6 respectively. There are no other known cases or families. We recently found a new Belgian family with mother and son with identical findings.

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PATIENTS AND METHODS: REPORT OF CLINICAL CASES

The first patient (case 1, female, born 24 January 1970) was known to have bilateral corneal opacities and impaired vision since early childhood. Her mother reported that her vision deteriorated until the age of 16 years. Her father, mother, and only sister as well as other members of the family had normal corneas. Her medical history was negative. She had no pain or redness. There was severe photophobia but no nystagmus.

A clinical examination was performed at the age of 20 years. Visual acuity was 0.16 right and 0.1 left with optimal correction of −9 and −9.5 D with contact lenses. Intraocular pressure was 17 mm Hg bilaterally. Biomicroscopy showed corneas of normal thickness and a smooth and regular epithelium. There were no signs of inflammation. The stroma showed a bilateral and symmetric homogeneous diffuse flaky clouding over the whole cornea in all layers of the stroma; frequent and small white opacities were found evenly distributed centrally, in the periphery, and anterior and posterior (Figs. 1 and 2). Clinical examination of the endothelium and Descemet's membrane was very difficult and not possible with specular microscopy.

FIG. 1.

FIG. 1.

FIG. 2.

FIG. 2.

A penetrating keratoplasty of the right eye was performed 18 October 1990 with postoperative vision of 0.8. The graft remained perfectly clear during the next 10 years. A lamellar keratoplasty of the left eye was performed 8 May 2000 resulting in a clear graft and corrected vision of 0.6.

The only child of this patient (case 2, a son, born 9 June 1998) was examined 1 month after birth because of bilateral corneal clouding. The opacities were visible from the first day of life. The eyes were not inflamed, and the corneas showed a picture similar to that in the mother, but with much less pronounced diffuse and flaky clouding homogeneously distributed over the whole cornea. A pediatric examination did not reveal any other abnormalities.

Examination with cycloplegia showed a normal fundus and a refractive error of +5 and +6. The child was followed during his first 2 years, and the corneal haze progressed slightly, making a refractive examination difficult. There was no nystagmus or strabismus visible. Vision at the age of 3 years was 2/5 in both eyes, determined by the Ffooks test.

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Light and Electron Microscopic Findings

The first corneal button in case 1 (full thickness) was immediately sectioned after transplantation into three parts for fixing in 4% buffered formalin, fixing in ice-cold 2% buffered glutaraldehyde, and freezing for stocking purpose. The second corneal button (lamellar) was bisected after the operation and fixed in the same way. The material fixed in formalin was processed in the normal way for light microscopy and stained with hematoxylin-eosin, periodic acid–Schiff, Masson's trichrome, Alcian blue, and Congo red. The corneal sections, fixed in glutaraldehyde, were processed for routine electron microscopy and embedded in epoxy resin.

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Light Microscopic Findings

The corneal button was of normal thickness. Normal epithelium rested on an uninterrupted Bowman's membrane of normal thickness. The stroma contained a normal population and distribution of keratocytes of normal appearance. The stromal lamellae were separated from each other in a regular manner. No infiltration, vessels, or inflammatory or storage material could be found. Descemet's membrane was intact and covered by normal endothelium.

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Electron Microscopic Findings

The corneal epithelium, its thin basement membrane, and Bowman's layer showed a normal ultrastructural appearance without inclusions. Between the normal collagen lamellae of the stroma, abnormal fibrillar layers were obvious (Fig. 3). These special fibrillar layers, rather homogeneously distributed throughout the whole stroma, were composed of straight, short, and long filaments of 12 to 18 nm diameter, randomly oriented and embedded in an electron lucent matrix (Fig. 4). The keratocytes were regularly distributed in the stroma and had a normal appearance without inclusions. Descemet's membrane was of normal thickness with a normal banding of the anterior portion; the endothelium did not show any special alterations.

FIG. 3.

FIG. 3.

FIG. 4.

FIG. 4.

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DISCUSSION

This is the third report of, as well as the third pedigree found in the literature with, congenital hereditary stromal dystrophy in which electron microscopic examination revealed the cause of the congenital corneal clouding, although the nature of the strange fibrillar material in the stroma remained obscure. 5,6 A few older reports can all be linked to the same French family. 7,8

Our family is not linked to the other families, and the mother is the first person in her family with the disease. The electron microscopic photographs of the stroma were identical to the published ones. 5,6 However we found a normal characteristic banding of the anterior portion of Descemet's membrane, as was found by Pouliquen et al., 6 but not by Witschel et al. 5 The inheritance follows a dominant pattern with a very high penetration rate. The gene has not yet been explored but can be looked for now that more families are known.

The aberrations in the stroma appear to be the result of disordered stromal fibrogenesis, which is the reason why they are detected very early in life. Our second case had a slightly hazy cornea at birth, which became more opaque during the first 2 years. His mother showed no further evolution after she was 16 years old. In the other families, the stromal opacities remained stationary during life, but they were not observed as early as ours; the children were known to have opacities shortly after birth but were not examined by the authors until the ages of 4 and 5 years or older. 5,6 There is probably corneal fibrogenesis after birth. This family presents with better vision than that of the other families; however, it is not known whether the difference in the banding of the anterior portion of Descemet's membrane is the cause of this variability. After penetrating keratoplasty, there were no clinical recurrences of the stromal pattern in our cases and in those in the literature. 5–8 However, as in other congenital opacities, deprivation amblyopia, strabismus, and high refractive errors are a difficult problem. The mother in our family had very good visual acuity after transplantation, and, although she has a high myopic refractive error, as in the other cases in the literature, she regained very good vision, which may mean a better prognosis for her child.

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Acknowledgment:

The authors thank Prof. Dr. Witschel (Freiburg, Germany) for reviewing and discussing the electron microscopic photographs.

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REFERENCES

1. Townsend WM. Congenital anomalies of the cornea. In: Kaufman HE, Barron BA, McDonald MB, eds. The cornea. Boston: Butterworth-Heinemann, 1998: 365–89.
2. Judge J, Waring GO, Blocker RJ. Congenital and neonatal corneal abnormalities. In: Leibowitz HM, Waring GO, ed. Corneal disorders. clinical diagnosis and management. Philadelphia: Saunders, 1998: 202–23.
3. Carpel EF, Sigelman RJ, Doughman DJ. Posterior amorphous corneal dystrophy. Am J Ophthalmol 1977; 83: 629–32.
4. Johnson AT, Folberg R, Vrabec MP, et al. The pathology of posterior amorphous corneal dystrophy. Ophthalmology 1990; 97: 104–9.
5. Witschel H, Fine BS, Grützner P, et al. Congenital hereditary stromal dystrophy of the cornea. Arch Ophthalmol 1978; 96: 1043–51.
6. Pouliquen Y, Lacombe E, Schreinzer C, et al. La dystrophie congénital héréditaire du stroma cornéen de Turpin. J Fr Ophtalmol 1979; 2: 115–25.
7. Desvignes P, Vigo. À propos d'un cas de dystrophie cornéenne parenchymateuse familiale à hérédite dominante. Bull Soc Ophtal Fr 1955; 20: 220–5.
8. Turpin R, Tisserand J, Sérane J. Opacités cornéennes héréditaires et congénitales réparties sur trois générations et atteignants deux jumelles monozygotes. Arch Ophtal (Paris) 1939; 3: 109–11.
Keywords:

Cornea; Dystrophy; Stromal dystrophy; Congenital corneal opacities; Dominant congenital stromal dystrophy

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