Cataract in Kniest Dysplasia

CLINICOPATHOLOGIC REPORTS, CASE REPORTS, AND SMALL CASE SERIES

SECTION EDITOR: W. RICHARD GREEN, MD

perception OS. Horizontal and ver- had a dishlike facies with button Cataract in Kniest tical corneal diameters were 12.5 mm nose and prominent eyes. Dysplasia: Clinicopathologic and 11.9 mm OD and 12.4 mm and Pars plana vitrectomy with len- Correlation 11.9 mm OS, respectively. Slitlamp sectomy was performed in the left examination of the right eye showed eye. The central anterior and poste- a deep anterior chamber and clear rior capsules were dissected with scis- Kniest dysplasia is a variant of the lens. The left eye had a shallow an- sors and placed in 2.5% glutaralde- spondyloepiphyseal dysplasias terior chamber, elongated ciliary pro- hyde for electron microscopy. The caused by an abnormal synthesis of cesses, and a dense white cataract vitreous base demonstrated re- collagen type II. In 1952, Kniest1 re- centrally, with the capsule showing tracted vitreous with severe anterior ported the first specific description a corrugated (wrinkled) surface. The loop traction, heavy deposits of pig- of a variety of chondrodystrophy that iris vessels were engorged, and a fine ments, and dense vitreous veils and he termed an atypical chondrodys- network of neovascularization, re- strands. Schlierenlike subretinal fluid trophy, which came to be known as sembling the vessels of the tunica vas- was drained through a superonasal Kniest dysplasia.1 culosa lentis, was present on the an- hole. Giant retinal macrocysts made A patient with Kniest dysplasia terior lens surface. Dense posterior flattening of the thinned, foreshort- usually is seen with characteristic synechiae were noted. Intraocular ened, cystic retina difficult. The retina round facies, midfacial flatness, and pressures were 14 mm Hg OD and 5 remained flat and attached for a proptosis. Radiologic findings are pa- mm Hg OS. month, after which it redetached and thognomic and differentiate this syn- Fundus examination results of eye became phthisical. drome from other bone dysplasias and the right eye showed prominent vit- Histopathologic examination of dwarfism.2 Histologically the syn- reous veils, liquefaction, syneresis, the lens capsule disclosed thick- drome is characterized by abnormal and a partial posterior vitreous de- ened anterior and posterior cap- cartilage with large chondrocytes em- tachment. Disc pallor was present, sules and metaplastic lens epithe- bedded in loosely woven matrix that with a cup-disc ratio of 0.3. The pe- lium. Transmission electron contains many empty spaces and gives ripheral retina had areas of lattice, ex- microscopy of the anterior capsule rise to the name Swiss cheese carti- tensive microcystoid degeneration, confirmed the aforementioned find- lage syndrome. The chondrocytes have and long oral bays. The fundus of the ings and additionally demonstrated dilated cisternae of endoplasmic re- left eye was not visible because of the loss of normal architecture of the lens ticulum.3 Abnormal organization of white cataract. Ultrasonography of epithelium. The metaplastic epithe- type II collagen has been found to be the right eye showed evidence of vit- lial cells were surrounded by fine fi- due to a gene mutation.4 reous degeneration with sparse ech- brillar and amorphous extracellular Kniest dysplasia is associated oes in the posterior third of the vit- matrix material, as well as basement with multiple ocular abnormalities.5 reous. The left eye had total closed membrane material (Figure 1 and Myopia, vitreous liquefaction and syn- funnel retinal detachment. Figure 2). The aberrant epithelial eresis, vitreous condensation, trac- Systemic examination find- cells were elongated and spindle tion at the vitreous base, areas of white ings showed abnormal growth with shaped and had swollen mitochon- without pressure at the retinal pe- flexion contractures, delayed mo- dria and dilated cisternae of endo- riphery, and extensive perivascular tor development, hearing loss, plasmic reticulum (Figure 2 and lattice degeneration are common find- muscle atrophy, and normal intel- Figure 3). Fine fibrillar collagen and ings. Cataracts tend to develop at an ligence. Radiographs showed verte- dystrophic calcification were also ap- early age and are firm in consis- bral defects, short tubular bones with parent (Figure 3). tency.5 We report the ultrastructural epiphyseal irregularities, and me- The posterior capsule tissue features of the lens capsule in a pa- taphyseal enlargement of the fe- showed aberrant lens epithelial cells tient with Kniest dysplasia. murs producing a typical “dumbbell- that had probably migrated into the shaped” appearance, along with posterior subcapsular plaque Report of a Case. A 4-year-old white platyspondyly, vertebral spurs, and (Figure 4). These cells with elec- girl was examined at the retina ser- clefts in the vertebrae. Photo- tron-dense granules had cystic mi- vice with a 6-month history of de- graphs showed that the patient had tochondria and dilated endoplas- creased vision in the left eye. Re- been born with short limbs and a hy- mic reticulum (Figure 5) similar sults of examination showed that her poplastic midface, and she devel- to the anterior subcapsular region. best-corrected visual acuity was 20/60 oped lumbar lordosis resulting in a These cells were also surrounded by OD (−5.00 diopters sphere) and light typical “about to dive” posture. She fine fibrillar collagen.

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N Metaplastic Lens Epithelium Dystrophic N Calcification

Figure 1. Electron micrograph of the thickened anterior lens capsule and Figure 3. Higher-magnification electron micrograph of the anterior metaplastic subcapsular epithelium surrounded by microfibrillar and subcapsular plaque. A metaplastic lens epithelial cell is surrounded by amorphous extracellular material. N indicates nuclei of epithelial cells basement membrane material. Fibrillar collagen and dystrophic calcification (original magnification ϫ2150). are also apparent (original magnification ϫ4600).

Figure 2. Electron micrograph of anterior subcapsular plaque consisting of Figure 4. Electron micrograph of the posterior subcapsular plaque consisting metaplastic lens epithelium surrounded by an extracellular matrix of fibrillar of fibrillogranular materials in which aberrant epithelial cells are embedded that collagen, basement membrane material, and calcific granules. N indicates contain electron-dense granules (original magnification ϫ2750). nuclei of epithelial cells (original magnification ϫ2750). Comment. Congenital severe myopia, vitreoretinal degeneration, and retinal detachment are known ocu- N lar abnormalities associated with M Kniest dysplasia.2 Previous studies showed a predominant defect in the type II collagen major fibril, which is a major constituent of the Dilated ER vitreous. It has also been postu- lated that collagen type IIA has an important role in the maturation and maintenance of the retina.6 M The predisposition for retinal detachment in these patients may be due to improper maturation of col-

N lagen 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 evi- dent in our patient. The mechanism 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 of cataract development in these pa- dilated endoplasmic reticulum (ER) as well as swollen mitochondria (M) (original magnification ϫ4600). tients has not been established.

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 Electron microscopy of the an- partment of Ophthalmology, Univer- emia, and a tender mass in the terior and posterior capsule of the lens sity of Florida College of Medicine, 580 superotemporal orbit. Extraocular showed aberrant epithelial cells with W Eighth St, Jacksonville, FL 32209 movements were limited in lateral dilated endoplasmic reticulum, for- (e-mail: [email protected]). and up gazes. The erythrocyte sedi- mation of collagenous fibrous tis- mentation rate was 61 mm/h and 1. Kniest W. Zur Abgrenzung der Dystosis enchon- sue, and dystrophic calcification. dralis von der Chondro dystrophie. Z Kinder- white blood cell count, 13200/µL These findings are reminiscent of the heilkd. 1952;70:633-640. (13.2ϫ109/L). Computed tomogra- changes seen in cartilage. The histo- 2. Rimoin DL, Siggers DC, Lachman RS, Silber- phy findings showed an ill-defined berg F. Metatropic dwarfism, the Kniest syn- pathologic changes in the lens indi- drome and the pseudoachondroplastic dyspla- mass in the lacrimal gland with a cate that it is involved in Kniest dys- sia. Clin Orthop. 1976;(114):70-82. central radiolucency, rim enhance- 3. Lachman RS, Rimoin DL, Hollister DW, et al. The plasia either primarily or secondarily. Kniest syndrome. Am J Roentgenol Radium Ther ment, and no bony changes Formation of abnormal subcapsular Nucl Med. 1975;123:805-814. (Figure 1). collagen plaques beneath the cap- 4. Weis MA, Wilkin DJ, Kim HJ, et al. Structurally The mass was surgically ex- abnormal type II collagen in a severe form of sules together with dystrophic calci- Kniest dysplasia caused by an exon 24 skipping plored via a skin-crease incision and fication may be responsible for the ab- mutation. J Biol Chem. 1998;273:4761-4768. appeared to consist of an abscess normally hard cataracts. The cataract 5. Maumenee IH, Traboulsi EI. The ocular find- containing yellow-green viscous ma- ings in Kniest dysplasia. Am J Ophthalmol. 1985; could also develop as a posterior cap- 100:155-160. terial. A culture yielded no growth, sular opacity and progress to a total 6. Siggers DC, Rimoin DL, Dorst JP, et al. The but biopsy findings of the cavity wall Kniest syndrome. Birth Defects. 1974;10:193- cataract. Another possible mecha- 208. revealed adenocarcinoma thought to nism for cataract development could 7. Tripathi RC, Cibis GW, Harris DJ, Tripathi BJ. represent a primary lacrimal neo- be abnormal lens fiber formation due Lowe’s syndrome. In: Cotlier E, Maumenee IH, plasm rather than metastasis be- Berman ER. Genetic Eye Diseases. New York, NY: to the metaplastic lens epithelial cells. Alan R Liss Inc; 1982:629-644. Birth Defects cause the tumor expressed both cy- Dilated endoplasmic reticulum in Original Article Series, vol 18, No. 6. tokeratins (CAM 5.2) and S100 cartilage chondrocytes and lens epi- 8. Tripathi RC, Cibis GW, Tripathi BJ. Pathogen- protein immunoreactivity. This im- esis of cataracts in patients with Lowe’s syn- thelial cells may be indicative of syndrome. Ophthalmology. 1986;93:1046-1051. munoprofile, while not diagnostic, thesis of abnormal protein and extra- is typical of salivary gland tumors in- cellular matrix material.6 Although cluding PLA.2 changes in Kniest dysplasia appear to Thepatientunderwentthorough be developmental, unilateral cases of Polymorphous Low-Grade systemic evaluation, including com- cataract and retinal detachment have Adenocarcinoma of puted tomography of the chest, abdo- been reported.5 the Lacrimal Gland men, and head. All investigation re- Our observation supports the sults were normal, and a lid-sparing theory that the underlying defect Malignancies constitute half of all exenteration, including the biopsy causing cataracts is primarily a col- epithelial tumors of the lacrimal track, was performed. lagen synthesis defect. Production of gland, with the majority being ad- abnormal glycosaminoglycans prob- enoid cystic carcinoma. Adenocar- Results. Histopathologic results re- ably has a minimal role in the patho- cinomas are much less common and vealed PLA of the lacrimal gland genesis of the ocular defects. Our generally demonstrate a poor prog- (Figure 2). The tumor cells were findings bear great similarity to the nosis. However, the recent applica- cytologically bland, showing mild histopathologic features described in tion of histological subtyping to this nuclear pleomorphism, and no mi- Lowe syndrome.7,8 The abnormali- group is leading to a better charac- toses were identified. However, there ties noted in Kniest dysplasia could terization of what appears to be a was extensive infiltration of the ad- be developmental, and a periodic heterogeneous collection.1 We pre- jacent tissue, and the tumor dis- comprehensive ophthalmic evalua- sent a rare case of polymorphous played a variety of architectural pat- tion of the patient is warranted. low-grade adenocarcinoma (PLA) of terns, including cribriform, tubular, the lacrimal gland and discuss the and fascicular areas along with solid K. V. Chalam, MD, PhD clinical manifestation and progno- cell nests. Some necrosis was seen Jacksonville, Fla sis in the context of similar tumors centrally, and infiltration of the ex- R. C. Tripathi, MD, PhD arising within the salivary glands. traocular muscle was present. How- B. J. Tripathi, PhD Columbia, SC Report of a Case. A 67-year-old man Vinay A. Shah, MD was initially seen with painless right Jacksonville upper eyelid swelling and conjunctival hyperemia across a 2-day pe- David Yee, MD riod. The patient had been previ- V. A. Pakalnis, MD ously asymptomatic, and old Columbia photographs were not available for review. Examination revealed him to The authors have no relevant finan- be afebrile with a visual acuity of cial interest in this article. 6/12 OD and 6/9 OS, 6 mm of pro- Figure 1. Axial computed tomographic scan Corresponding author and re- ptosis, 3-mm inferior globe displace- shows a mass in the right lacrimal gland with a prints: K. V. Chalam, MD, PhD, De- ment, temporal conjunctival hyper- central radiolucent area.

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