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Cataract in Kniest Dysplasia: Clinicopathologic Correlation
Arch Ophthalmol. 2004;122:913-915.
Kniest dysplasia is a variant of the spondyloepiphyseal dysplasias caused by an abnormal synthesis of collagen type II. In 1952, Kniest1 reported the first specific description of a variety of chondrodystrophy that he termed an atypical chondrodystrophy, which came to be known as Kniest dysplasia. 1
A patient with Kniest dysplasia usually is seen with characteristic round facies, midfacial flatness, and proptosis. Radiologic findings are pathognomic and differentiate this syndrome from other bone dysplasias and dwarfism.2 Histologically the syndrome is characterized by abnormal cartilage with large chondrocytes embedded in loosely woven matrix that contains many empty spaces and gives rise to the name Swiss cheese cartilage syndrome. The chondrocytes have dilated cisternae of endoplasmic reticulum.3 Abnormal organization of type II collagen has been found to be due to a gene mutation.4
Kniest dysplasia is associated with multiple ocular abnormalities.5 Myopia, vitreous liquefaction and syneresis, vitreous condensation, traction at the vitreous base, areas of white without pressure at the retinal periphery, and extensive perivascular lattice degeneration are common findings. Cataracts tend to develop at an early age and are firm in consistency.5 We report the ultrastructural features of the lens capsule in a patient with Kniest dysplasia.
Report of a Case
A 4-year-old white girl was examined at the retina service with a 6-month history of decreased vision in the left eye. Results of examination showed that her best-corrected visual acuity was 20/60 OD (–5.00 diopters sphere) and light perception OS. Horizontal and vertical corneal diameters were 12.5 mm and 11.9 mm OD and 12.4 mm and 11.9 mm OS, respectively. Slitlamp examination of the right eye showed a deep anterior chamber and clear lens. The left eye had a shallow anterior chamber, elongated ciliary processes, and a dense white cataract centrally, with the capsule showing a corrugated (wrinkled) surface. The iris vessels were engorged, and a fine network of neovascularization, resembling the vessels of the tunica vasculosa lentis, was present on the anterior lens surface. Dense posterior synechiae were noted. Intraocular pressures were 14 mm Hg OD and 5 mm Hg OS.
Fundus examination results of the right eye showed prominent vitreous veils, liquefaction, syneresis, and a partial posterior vitreous detachment. Disc pallor was present, with a cup-disc ratio of 0.3. The peripheral retina had areas of lattice, extensive microcystoid degeneration, and long oral bays. The fundus of the left eye was not visible because of the white cataract. Ultrasonography of the right eye showed evidence of vitreous degeneration with sparse echoes in the posterior third of the vitreous. The left eye had total closed funnel retinal detachment.
Systemic examination findings showed abnormal growth with flexion contractures, delayed motor development, hearing loss, muscle atrophy, and normal intelligence. Radiographs showed vertebral defects, short tubular bones with epiphyseal irregularities, and metaphyseal enlargement of the femurs producing a typical "dumbbell-shaped" appearance, along with platyspondyly, vertebral spurs, and clefts in the vertebrae. Photographs showed that the patient had been born with short limbs and a hypoplastic midface, and she developed lumbar lordosis resulting in a typical "about to dive" posture. She had a dishlike facies with button nose and prominent eyes.
Pars plana vitrectomy with lensectomy was performed in the left eye. The central anterior and posterior capsules were dissected with scissors and placed in 2.5% glutaraldehyde for electron microscopy. The vitreous base demonstrated retracted vitreous with severe anterior loop traction, heavy deposits of pigments, and dense vitreous veils and strands. Schlierenlike subretinal fluid was drained through a superonasal hole. Giant retinal macrocysts made flattening of the thinned, foreshortened, cystic retina difficult. The retina remained flat and attached for a month, after which it redetached and eye became phthisical.
Histopathologic examination of the lens capsule disclosed thickened anterior and posterior capsules and metaplastic lens epithelium. Transmission electron microscopy of the anterior capsule confirmed the aforementioned findings and additionally demonstrated loss of normal architecture of the lens epithelium. The metaplastic epithelial cells were surrounded by fine fibrillar and amorphous extracellular matrix material, as well as basement membrane material (Figure 1 and Figure 2). The aberrant epithelial cells were elongated and spindle shaped and had swollen mitochondria and dilated cisternae of endoplasmic reticulum (Figure 2 and Figure 3). Fine fibrillar collagen and dystrophic calcification were also apparent (Figure 3).
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Figure 1. Electron micrograph of the thickened anterior lens capsule and metaplastic subcapsular epithelium surrounded by microfibrillar and amorphous extracellular material. N indicates nuclei of epithelial cells (original magnification x2150).
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Figure 2. Electron micrograph of anterior subcapsular plaque consisting of metaplastic lens epithelium surrounded by an extracellular matrix of fibrillar collagen, basement membrane material, and calcific granules. N indicates nuclei of epithelial cells (original magnification x2750).
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Figure 3. Higher-magnification electron micrograph of the anterior subcapsular plaque. A metaplastic lens epithelial cell is surrounded by basement membrane material. Fibrillar collagen and dystrophic calcification are also apparent (original magnification x4600).
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The posterior capsule tissue showed aberrant lens epithelial cells that had probably migrated into the posterior subcapsular plaque (Figure 4). These cells with electron-dense granules had cystic mitochondria and dilated endoplasmic reticulum (Figure 5) similar to the anterior subcapsular region. These cells were also surrounded by fine fibrillar collagen.
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Figure 4. Electron micrograph of the posterior subcapsular plaque consisting of fibrillogranular materials in which aberrant epithelial cells are embedded that contain electron-dense granules (original magnification x2750).
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Figure 5. Electron micrograph of posterior lens capsule and aberrant lens epithelial cells that have migrated on the internal aspect of the capsule. The cells (N, nuclei) contain electron-dense granules and dilated endoplasmic reticulum (ER) as well as swollen mitochondria (M) (original magnification x4600).
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Comment
Congenital severe myopia, vitreoretinal degeneration, and retinal detachment are known ocular abnormalities associated with Kniest dysplasia.2 Previous studies showed a predominant defect in the type II collagen major fibril, which is a major constituent of the vitreous. It has also been postulated that collagen type IIA has an important role in the maturation and maintenance of the retina.6 The predisposition for retinal detachment in these patients may be due to improper maturation of collagen type IIA.
Early development of cataracts has been believed to be related to the pathogenesis of the disease.5 The cataracts are unusually hard for the age and require phacofragmentation rather then aspiration,5 as was evident in our patient. The mechanism of cataract development in these patients has not been established.
Electron microscopy of the anterior and posterior capsule of the lens showed aberrant epithelial cells with dilated endoplasmic reticulum, formation of collagenous fibrous tissue, and dystrophic calcification. These findings are reminiscent of the changes seen in cartilage. The histopathologic changes in the lens indicate that it is involved in Kniest dysplasia either primarily or secondarily. Formation of abnormal subcapsular collagen plaques beneath the capsules together with dystrophic calcification may be responsible for the abnormally hard cataracts. The cataract could also develop as a posterior capsular opacity and progress to a total cataract. Another possible mechanism for cataract development could be abnormal lens fiber formation due to the metaplastic lens epithelial cells. Dilated endoplasmic reticulum in cartilage chondrocytes and lens epithelial cells may be indicative of synthesis of abnormal protein and extracellular matrix material.6 Although changes in Kniest dysplasia appear to be developmental, unilateral cases of cataract and retinal detachment have been reported.5
Our observation supports the theory that the underlying defect causing cataracts is primarily a collagen synthesis defect. Production of abnormal glycosaminoglycans probably has a minimal role in the pathogenesis of the ocular defects. Our findings bear great similarity to the histopathologic features described in Lowe syndrome.7-8 The abnormalities noted in Kniest dysplasia could be developmental, and a periodic comprehensive ophthalmic evaluation of the patient is warranted.
The authors have no relevant financial interest in this article.
AUTHOR INFORMATION
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K. V. Chalam, MD, PhD
Jacksonville, Fla
R. C. Tripathi, MD, PhD;
B. J. Tripathi, PhD
Columbia, SC
Vinay A. Shah, MD
Jacksonville
David Yee, MD;
V. A. Pakalnis, MD
Columbia
Corresponding author and reprints: K. V. Chalam, MD, PhD, Department of Ophthalmology, University of Florida College of Medicine, 580 W Eighth St, Jacksonville, FL 32209 (e-mail: kvchalam{at}aol.com).
REFERENCES
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1. Kniest W. Zur Abgrenzung der Dystosis enchondralis von der Chondro dystrophie. Z Kinderheilkd. 1952;70:633-640.
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2. Rimoin DL, Siggers DC, Lachman RS, Silberberg F. Metatropic dwarfism, the Kniest syndrome and the pseudoachondroplastic dysplasia. Clin Orthop. 1976;(114):70-82.
3. Lachman RS, Rimoin DL, Hollister DW, et al. The Kniest syndrome. Am J Roentgenol Radium Ther Nucl Med. 1975;123:805-814.
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4. Weis MA, Wilkin DJ, Kim HJ, et al. Structurally abnormal type II collagen in a severe form of Kniest dysplasia caused by an exon 24 skipping mutation. J Biol Chem. 1998;273:4761-4768.
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5. Maumenee IH, Traboulsi EI. The ocular findings in Kniest dysplasia. Am J Ophthalmol. 1985;100:155-160.
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6. Siggers DC, Rimoin DL, Dorst JP, et al. The Kniest syndrome. Birth Defects. 1974;10:193-208.
7. Tripathi RC, Cibis GW, Harris DJ, Tripathi BJ. Lowe's syndrome. In: Cotlier E, Maumenee IH, Berman ER. Genetic Eye Diseases. New York, NY: Alan R Liss Inc; 1982:629-644. Birth Defects Original Article Series, vol 18, No. 6.
8. Tripathi RC, Cibis GW, Tripathi BJ. Pathogenesis of cataracts in patients with Lowe's syndrome. Ophthalmology. 1986;93:1046-1051.
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