Cataract in Kniest Dysplasia: Clinicopathologic Correlation

Kniest dysplasia is a variant of the spondyloepiphyseal dysplasias causedby an abnormal synthesis of collagen type II. In 1952, Kniest¹ reportedthe first specific description of a variety of chondrodystrophy that he termedan atypical chondrodystrophy, which came to be knownas Kniest dysplasia.¹

A patient with Kniest dysplasia usually is seen with characteristicround facies, midfacial flatness, and proptosis. Radiologic findings are pathognomicand differentiate this syndrome from other bone dysplasias and dwarfism.² Histologically the syndrome is characterized byabnormal cartilage with large chondrocytes embedded in loosely woven matrixthat contains many empty spaces and gives rise to the name Swiss cheese cartilage syndrome. The chondrocytes have dilated cisternaeof endoplasmic reticulum.³ Abnormal organizationof 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, vitreouscondensation, traction at the vitreous base, areas of white without pressureat the retinal periphery, and extensive perivascular lattice degenerationare common findings. Cataracts tend to develop at an early age and are firmin consistency.⁵ We report the ultrastructuralfeatures of the lens capsule in a patient with Kniest dysplasia.

A 4-year-old white girl was examined at the retina service with a 6-monthhistory of decreased vision in the left eye. Results of examination showedthat her best-corrected visual acuity was 20/60 OD (−5.00 diopters sphere)and light perception OS. Horizontal and vertical corneal diameters were 12.5mm and 11.9 mm OD and 12.4 mm and 11.9 mm OS, respectively. Slitlamp examinationof the right eye showed a deep anterior chamber and clear lens. The left eyehad a shallow anterior chamber, elongated ciliary processes, and a dense whitecataract 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 theanterior lens surface. Dense posterior synechiae were noted. Intraocular pressureswere 14 mm Hg OD and 5 mm Hg OS.

Fundus examination results of the right eye showed prominent vitreousveils, liquefaction, syneresis, and a partial posterior vitreous detachment.Disc pallor was present, with a cup-disc ratio of 0.3. The peripheral retinahad 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 degenerationwith sparse echoes in the posterior third of the vitreous. The left eye hadtotal 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 epiphysealirregularities, and metaphyseal enlargement of the femurs producing a typical"dumbbell-shaped" appearance, along with platyspondyly, vertebral spurs, andclefts in the vertebrae. Photographs showed that the patient had been bornwith short limbs and a hypoplastic midface, and she developed lumbar lordosisresulting in a typical "about to dive" posture. She had a dishlike facieswith 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 andplaced in 2.5% glutaraldehyde for electron microscopy. The vitreous base demonstratedretracted vitreous with severe anterior loop traction, heavy deposits of pigments,and dense vitreous veils and strands. Schlierenlike subretinal fluid was drainedthrough a superonasal hole. Giant retinal macrocysts made flattening of thethinned, foreshortened, cystic retina difficult. The retina remained flatand attached for a month, after which it redetached and eye became phthisical.

Histopathologic examination of the lens capsule disclosed thickenedanterior and posterior capsules and metaplastic lens epithelium. Transmissionelectron microscopy of the anterior capsule confirmed the aforementioned findingsand additionally demonstrated loss of normal architecture of the lens epithelium.The metaplastic epithelial cells were surrounded by fine fibrillar and amorphousextracellular matrix material, as well as basement membrane material (Figure 1 and Figure 2). The aberrant epithelial cells were elongated and spindleshaped and had swollen mitochondria and dilated cisternae of endoplasmic reticulum(Figure 2 and Figure 3). Fine fibrillar collagen and dystrophic calcificationwere also apparent (Figure 3).

The posterior capsule tissue showed aberrant lens epithelial cells thathad probably migrated into the posterior subcapsular plaque (Figure 4). These cells with electron-dense granules had cystic mitochondriaand dilated endoplasmic reticulum (Figure5) similar to the anterior subcapsular region. These cells werealso surrounded by fine fibrillar collagen.

Congenital severe myopia, vitreoretinal degeneration, and retinal detachmentare known ocular abnormalities associated with Kniest dysplasia.² Previousstudies showed a predominant defect in the type II collagen major fibril,which is a major constituent of the vitreous. It has also been postulatedthat collagen type IIA has an important role in the maturation and maintenanceof the retina.⁶ The predisposition for retinaldetachment in these patients may be due to improper maturation of collagentype IIA.

Early development of cataracts has been believed to be related to thepathogenesis of the disease.⁵ The cataractsare unusually hard for the age and require phacofragmentation rather thenaspiration,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 lensshowed aberrant epithelial cells with dilated endoplasmic reticulum, formationof collagenous fibrous tissue, and dystrophic calcification. These findingsare reminiscent of the changes seen in cartilage. The histopathologic changesin the lens indicate that it is involved in Kniest dysplasia either primarilyor secondarily. Formation of abnormal subcapsular collagen plaques beneaththe capsules together with dystrophic calcification may be responsible forthe abnormally hard cataracts. The cataract could also develop as a posteriorcapsular opacity and progress to a total cataract. Another possible mechanismfor cataract development could be abnormal lens fiber formation due to themetaplastic lens epithelial cells. Dilated endoplasmic reticulum in cartilagechondrocytes and lens epithelial cells may be indicative of synthesis of abnormalprotein and extracellular matrix material.⁶ Althoughchanges in Kniest dysplasia appear to be developmental, unilateral cases ofcataract and retinal detachment have been reported.⁵

Our observation supports the theory that the underlying defect causingcataracts is primarily a collagen synthesis defect. Production of abnormalglycosaminoglycans probably has a minimal role in the pathogenesis of theocular defects. Our findings bear great similarity to the histopathologicfeatures described in Lowe syndrome.^7,8 Theabnormalities noted in Kniest dysplasia could be developmental, and a periodiccomprehensive ophthalmic evaluation of the patient is warranted.

The authors have no relevant financial interest in this article.

Corresponding author and reprints: K. V. Chalam, MD, PhD, Departmentof Ophthalmology, University of Florida College of Medicine, 580 W EighthSt, Jacksonville, FL 32209 (e-mail: kvchalam@aol.com).