Ocular Findings in Kenny's Syndrome James R. Boynton, MD; Thomas R. Pheasant, MD; Bruce L. Johnson, MD; Daniel B. Levin, MD; Barbara W. Streeten, MD

\s=b\In 1966, Kenny described two pa- 1966, Kenny and Linarelli de- and marginally low potassium levels also tients with an unusual congenital syn- scribed an unusual congenital syn¬ were noted. Hearing and dentition were drome including dwarfism, thickened long drome.' A mother and son exhibited abnormal. Intelligence and test results of bone cortex, transient hypocalcemia, and the following characteristics: low pituitary function were normal. At age 10, normal intelligence. These and other birth clo¬ height and bone age were both retarded. weight, dwarfism, delayed Skull showed bilateral were de- roentgenograms patients previously incorrectly sure of the anterior fontanel, uniquely lobe calcifications. films of scribed as Ocular temporal X-ray "myopic." findings in thickened long bone cortex with the long bones disclosed internal cortical four subjects ranged from uncomplicated stenotic medullary cavities,2 transient thickening and stenotic medullary cavi¬ nanophthalmos with hyperopia to extreme hypocalcemia with hyperphosphate- ties. pseudopapilledema, vascular tortuosity, mia leading to tetany, and normal Physically, the patient appeared minia¬ and macular crowding. Postmortem find- mentation. To our knowledge, only ture with a prominent forehead, microph- ings from one patient showed calcium two additional reports of this syn¬ thalmos, and micrognathia (Fig 1). Height deposits demonstrable only by special drome have since this was 102 cm. The sternum was slightly appeared'·4 orig¬ bowed histochemical stains that were distributed inal The ex¬ anteriorly. description. ophthalmic At age 3 she was seen because of a large uniquely in the . This distribution amination in all cases has been incom¬ right . The left eye was patched differed from the pattern seen in The incidence of greatly plete. reported "my¬ for several months, but there was no band keratopathy. Retinal calcification opia" is erroneous, and actually refers change in fixation preference. A bi medial was also an unusual feature. Because one to hypermetropia. This article de¬ recession was performed with only partial patient exhibited a pseudodoubling of the scribes the ocular findings in four cosmetic improvement, and the following optic papilla, the literature was reviewed. patients with Kenny's syndrome, in¬ year a recess-resect procedure was done on We conclude that no convincing case of cluding histologie examination results the right eye. During surgery, the was rectus true doubling of the has been from one case. exposed beneath the lateral described. Ophthalmologists should be insertion when this muscle was severed from the alert for undiagnosed electrolyte abnor- REPORT OF CASES* . Postoperatively, the media in the right eye were cloudy and a vitreous malities, in pa- Case 1.—The was born of normal especially hypocalcemia, patient hemorrhage was diagnosed. Two months tients with parents and exhibited slow after an Kenny's syndrome. growth later both fundi were visualized. The right uneventful She was first admit¬ (Arch Ophthalmol 97:896-900, 1979) delivery. disc was blurred and the macular area of ted to the at age 9 months with hospital each eye was described as gray. At age 5, fever, dwarfism, and retarded bone tetany, vision was recorded as counting fingers at Accepted for publication Nov 13, 1978. age. A of diagnosis hypoparathyroidism 122 cm in the right eye and 20/200 in the From the Department of , was made and vitamin D insti¬ therapy left eye. The of the eye was Warsaw Medical Group, PC, Warsaw, NY (Drs tuted. admissions because of fever right Boynton and Levin); Department of Ophthalmol- Multiple elevated and gray inferotemporally. and convulsions followed, accom¬ ogy, University of Rochester, Rochester, NY (Dr usually The patient was not seen again until she upper disease. Boynton); Division of Ophthalmology, Retina panied by respiratory Hypo¬ was 9. Vision in the right eye was hand S. calcemia and were Service, Milton Hershey Medical Center, hyperphosphatemia motion due to a dense . An early Hershey, Pa (Dr Pheasant); Department of documented electro¬ repeatedly. Sporadic band keratopathy was noted. Shortly of Pittsburgh School of abnormalities such as Pathology, University lyte hypernatremia an acute in Medicine (Dr Johnson); and State University of thereafter, developed New York, Upstate Medical Center, Syracuse (Dr the right eye with a flat anterior chamber. Streeten). *All four of the patients reported here were A posterior sclerotomy and aspiration Reprint requests to Warsaw Medical Group, seen by Frederic M. Kenny, MD, who confirmed were performed. PC, Warsaw, NY 14569 (Dr Boynton). the diagnosis. We first examined the patient at age 12.

Downloaded From: http://archopht.jamanetwork.com/ by a University of Pittsburgh User on 05/13/2015 Her best corrected vision was 20/800 in the dilated tortuous arterial and venous sys¬ patient (Fig 5). He was 135 cm tall. Best right eye and 20/200 in the left eye. The tems. Perivascular hyperfluorescence corrected vision was 20/30 in each eye with in the left eye was + 24.00 proved to be tortuous vessels viewed end on a +9.25 sphere in the right eye and a +9.75 diopters. The fundus of the right eye was and out of focus. As the study progressed sphere in the left eye. measured 9 obscured by a membrane secondary to the there was no increase in perivascular fluo¬ mm in diameter. Optic discs appeared lens extraction. Corneas measured 8 mm in rescence to imply leakage or loss of compe¬ slightly elevated with blurred margins and diameter and exhibited band keratopathy, tence of the retinal vasculature. The retina tortuous retinal vessels (Fig 6). Findings greater on the right. The left fundus was appeared crowded, as if confined to a from the remainder of the ocular examina¬ filled with multiple, dilated, tortuous smaller than normal space. The fovea was tion were normal. vessels. The entire retina appeared swollen surrounded by a capillary free zone smaller Case 3.-The 50-year-old mother of and abnormal, especially in the region than expected, an estimated 250 µ rather patient 2 was also examined. She had a about the optic nerve. The vascular pattern than 500 µ. There was no late hyperfluores¬ history of mild diabetes and was under 117 combined with these highlights presented cence or dye leakage. cm in height. Vision was 20/25 with a the deceptive picture of an accessory optic B-scan ultrasonography showed a single + 5.75, +1.75 x 130° in the right eye and nerve head (Fig 2). nerve pattern and a globe 13 mm in length 20/40 with a +6.50, +1.25 x 60° in the left Photographs, however, disclosed a single (Fig 4). The nerve pattern appeared slight¬ eye. Corneas measured 10 mm in diameter. elevated optic nerve head with tortuous, ly enlarged relative to the size of the globe. The fundi were unremarkable. redundant retinal circulation simulating Roentgenograms of the optic foramina Case 4.—The patient enjoyed good health an accessory above. The retinal were unremarkable. until age 5, at which time he experienced pigment epithelium was prominent in the Case 2.—The mother and son originally an episode of tetany that was treated posterior pole with pigment clumping in described by Kenny in 1966 recently were successfully with orally administered cal¬ the parafoveal region. Fluorescein angiog¬ examined. Their systemic findings are cium. Subsequently, he was begun on vi¬ raphy confirmed a single retinal circula¬ detailed in that report. The 13-year-old boy tamin D therapy. At age 8, growth re¬ tion (Fig 3). Dye transit demonstrated had a facial appearance similar to the first tardation was apparent. Extensive clinical

Fig 1.—Facial appearance of a 13-year-old Fig 2.—Left eye: retinal vessels are Fig 3.—Left eye: fluorescein angiogram, girl, characteristic of Kenny's syndrome tortuous and dilated; disc is blurred and arterial phase. Single tortuous vascular (case 1) elevated. Confluence of vessels combined system is present. There was no leakage with unusual retinal highlights simulates of fluorescein in later photographs (case "accessory disc" superotemporal to nerve 1)- head. Macular area is deeply pigmented and poorly defined (case 1).

Fig 4.—Left eye: B-scan ultrasonogram Fig 5.—Characteristic facial appearance of Fig 6.—Left eye: disc is slightly elevated demonstrates microphthalmos, globe a 13-year-old boy with Kenny's syndrome and vasculature moderately tortuous measuring 13 mm anteroposteriorly. Optic (case 2). (case 2). nerve pattern (large arrow) is slightly larg¬ er than expected for eye this size. Distance between range lines (small arrows) is 10 mm (case 1).

Downloaded From: http://archopht.jamanetwork.com/ by a University of Pittsburgh User on 05/13/2015 Fig 7.—Basal ganglia contains numerous irregular calcium depos¬ Fig 8.—Optic disc is elevated, lacks physiologic cup, but is not its and mineralized thick-walled vessel (hematoxylin-eosin, origi¬ edematous. Scierai aperture is slightly narrow (hematoxylin- nal magnification 60). eosin, original magnification 35).

Fig 9.—Low-power view of central cornea. Superficial stroma is uninvolved while deeper stroma, which is darker staining, contains abundant calcium (Von Kossa, original magnification X35).

Fig 10—Termination of corneal calcification zone. Black-staining keratocytic nuclei are heavily calcified and abundant fine gran¬ ules of calcium are present in collagen lamellae. In contrast, uninvolved upper left portion of field contains pale-staining keratocytic nuclei and no calcium deposits in collagen (Von Kossa, original magnification 350).

Fig 11.—Periphery of zone of corneal calcification shows abrupt, curved termination. In this area, mineralization involves superfi¬ cial stroma but Bowman's layer is spared throughout its length (Von Kossa, original magnification 60).

Fig 12.—Peripheral retina shows heavy calcium impregnation (black) of cytoplasm of Müller cells beneath internal limiting membrane (small arrows). Darker-staining nuclei of ganglion cells (large arrows) and many nuclei in bipolar cell layer also contain calcium (Von Kossa, original magnification 350).

Downloaded From: http://archopht.jamanetwork.com/ by a University of Pittsburgh User on 05/13/2015 A full elevated testing disclosed undetectable levels of of both corneas showed a distribu¬ congenitally disc, peculiar with blurred and tortuous parathyroid hormone in the presence of tion pattern of calcium. The central stroma margins was seen in three and serum hypocalcemia and hyperphospha- showed no detectable deposits within its vessels, patients temia. X-ray films showed internal cortical superficial one quarter. The deeper stromal histologically confirmed in one case. thickening of the long bones with medulla¬ layers, however, disclosed prominent cal¬ This type of nerve head is common in ry stenosis. cification that was most pronounced hyperopic eyes, although extreme hy¬ The only ophthalmic record available throughout the central midstroma (Fig 9). peropia and microphthalmos may ex¬ indicated a vision of 20/40 in each eye, This consisted of heavy calcification within ist with relatively normal-appearing achieved with a correction of nuclei numerous +9.00, keratocytic with fine discs." nerve head sections in + 2.00 x 90° in the right eye and within the lamellae of Optic +11.00, deposits collagen case 4 showed re¬ +1.50 90° in the left eye. The fundi this region (Fig 10). The central zone of pseudopapilledema from a or were noted to show "pseudoneuritis" with calcification terminated rather abruptly in sulting crowding compres¬ sion of the and nervous tissue in tortuous vessels. a curved, arc-shaped edge, which at this glial At age 19 he had a respiratory and point approached Bowman's layer (Fig 11). the region of the disc. Presumably a cardiac arrest during an upper respiratory The peripheral stroma failed to show small scierai canal must accommodate illness. At the time of his death, blood detectable calcium deposition. Alcian blue a normal number of axons and chemistry values were sodium, 123 mEq/L; stains showed excessive amounts of muco- elements. 2.6 supporting potassium, mEq/L; chloride, 85 mEq/L; polysaccharides in keratocytes, which con¬ It is also possible that a small scierai carbon dioxide, 22 mM/L; and calcium, 6.9 tained abundant calcifié deposits. This aperture could compromise the flow mEq/L. correlated well with the calcium histochem¬ of Altered flow At autopsy, all organs were small, con¬ ical stains in that abundant mucopolysac- axoplasm. axoplasmic be a factor in the of sistent with dwarfism. Extraocular abnor¬ charides were present only in the zone of may production malities were limited to the bones, brain, pronounced calcification. Deseemet's mem¬ .7 The small focal and a total absence of any parathyroid brane was spared throughout its length. drusen present in case 4 are certainly tissue. The bones showed internal cortical Heavy deposits of calcium were present in consistent with this hypothesis. If thickening with medullary stenosis. The the corneal endothelium, while less numer¬ indeed a small scierai canal causes a calvarium was thin and the anterior fonta- ous granules were seen within the endothe¬ holdup of axoplasmic flow, which in nel was Brain abnormalities included lial cells the trabecular meshwork open. lining turn results in swelling of the nerve brachycephaly and a partial Arnold-Chiari beams. these histochemical By methods, fibers anterior to the lamina cribrosa, malformation with congenital tonsillar only trace amounts of calcium were noted there be an element of disc herniation. There was considerable calcifi¬ in the lens nucleus and anterior vitreous. may true some cases cation of the basal ganglia. Calcospherites Calcium was demonstrable in the and swelling present. Perhaps and psammoma-like bodies were found in ciliary epithelium. Rather heavy deposition regarded in the past as pseudopapil¬ this region, and many capillaries contained of calcium was present within the inner ledema are in fact a very low-grade calcific deposits (Fig 7). Multiple hemi¬ one half of the preequatorial retina. The secondary to local ana¬ spheric gyral abnormalities were present. heaviest concentrations were present in tomic factors. Similar cases in chil¬ The cerebellum showed bilateral calcifica¬ the cytoplasm of Müller cells near the dren have been termed "buried drus¬ tion of the dentate nuclei, gliosis, and internal membrane and in the limiting en." It may be that early in life there shrinkage of the folia. ganglion cell nuclei (Fig 12). Lesser is mild disc that later results The enucleated were fixed in amounts were seen nerve swelling eyes phos¬ in the fiber layer in drusen phate-buffered 10% formaldehyde solution. and the nuclei of scattered cells in the inner deposition. The fundus in case 1 is an Both were nanophthalmic, the right mea¬ portion of the bipolar cell layer. Only rare picture suring 17.5 17.5 16.5 mm and the left endothelial cells of a few retinal vessels example of extreme pseudopapillede¬ 17 x 17 x 16.5 mm. The clear corneas contained calcium. No calcium was de¬ ma. Convergence of tortuous vessels measured 9.5 x 8.5 mm. On cut section, tected within the outer retina. Small combined with light reflexes from the both corneas were of slightly increased amounts were present in occasional astro- unusual retinal topography produce thickness 1 mm measuring peripherally cytes on the disc surface and except for the the deceptive picture of a doubling of and 0.7 mm No intraocular calcified drusen-like centrally. bodies noted in the the optic nerve head (Fig 1). Fluores¬ abnormalities were noted on gross exami¬ none was seen hematoxylin-eosin sections, cein shows a nation. in or angiography single Microscopically, hematoxylin- the disc substance attached optic retinal circu¬ eosin-stained sections showed elevated nerves. extremely hypervascular lation with optic discs associated with slightly narrow reduplications simulating scierai The discs a "double There is apertures (Fig 8). COMMENT papilla." pigment appeared swollen with lateral displacement epithelial clumping in the macula and of the peripapillary retina due to a bulging There is a related spectrum of a crowded appearance of the posterior of the edge of the disc tissue usually seen in ocular findings in the above cases. retinal circulation. Many macular ab¬ papilledema. Capillaries were slightly in¬ Patient 3 had moderate nanophthal- normalities have been described in creased in this lateral bulge. The left disc mos and but otherwise and contained several small calcified drusen- hyperopia, microphthalmic nanophthalmic normal eyes. Patients 2 and 4 exhib¬ It is that some of like bodies within the nerve fiber bundles eyes.""'- possible ited macular are due anterior to the fibrous of high hyperopia, nanophthalmos these conditions to portion the lami¬ with na cribrosa. pseudopapilledema, and retinal crowding of the retinal elements into Histochemical stains (Von Kossa and vascular tortuosity. Patient 1 demon¬ a small scierai shell. Folds in the reti¬ Dahl's modification of the alizarin red) for strated severe microphthalmos of 13 na have been seen in small eyes, the demonstration of the calcium were mm with extreme pseudopapilledema presumably on this basis." performed on sections of both eyes. In and macular crowding. Although nan- Case 1 represents an example of contrast to the hematoxylin-eosin sections, ophthalmic eyes may be predisposed pseudodoubling of the optic nerve. A where no calcification was detectable, the to angle closure the number of articles histochemical stains for calcium indicated glaucoma,5 only report duplicated such case was seen in an eye in which or doubled discs and nerves.1'·48 prominent amounts within the cornea. The optic a mature cataract developed. The Analysis of these studies shows not corneal epithelium contained abundant anterior chamber calcium within both the nuclei and cyto¬ angles examined one convincingly documented case. in case 4 plasm. This was not present in all cells, but histologically appeared small, Duke-Elder's volume on congenital was heaviest in those of the basal layer. but normally open. These eyes were 17 abnormalities'" simply quotes the Bowman's layer was spared. The stromas mm in diameter. literature on the subject, devoting a

Downloaded From: http://archopht.jamanetwork.com/ by a University of Pittsburgh User on 05/13/2015 section to double optic nerves without cium, the deposition of calcium is calcium deposition. Although vascular questioning the entity. We believe confined to heavy infiltration of Bow¬ factors have in the past been hypothe¬ that true duplication of the optic man's layer. In sharp contrast, Bow¬ sized as playing a role in metastatic nerve head does not exist. man's layer was not involved in this calcification, especially of the CNS,22 Abnormal calcium metabolism is a case, but deposits were seen within the findings in this case do not prominent feature of Kenny's syn¬ the basal cells of the corneal epithe¬ support such a suggestion in either drome. The exact nature of these lium, the central, mid-, and deep stro¬ the retina or avascular cornea. abnormalities has not been deter¬ ma, and the endothelial cells. These The tiny focal drusen deposits in the mined, but several features have findings are similar in some respects optic nerve head may relate to the disc emerged. Bouts of hypocalcemia are to the unusual corneal calcification swelling, although it is possible they easily triggered by minor systemic reported by Berkow et al2" in a patient are an incidental finding.2' Their rela¬ insults and respond to calcium and with secondary hyperparathyroidism. tionship to the other CNS calcifica¬ vitamin D therapy. At the present In both, the heaviest concentration of tions is uncertain. time, the relationship of this therapy calcium is present within the nuclei of It is important for ophthalmologists to tissue calcium deposition is un¬ epithelial cells and keratocytes. The to be aware of this syndrome since known. current case differs in the peculiar they may be called on to examine such Patient 4 is the only known patient zonal distribution and the much a patient because of poor vision, small with Kenny's syndrome to be studied greater amounts of calcium visible eyes, "papilledema," or other ocular at autopsy. There was a total absence within the stromal collagen lamellae. abnormalities. If the diagnosis of of parathyroid tissue despite an The abundant mucopolysaccharide Kenny's syndrome is not known or extensive search of the soft tissues of deposition in the areas of heavy suspected, dangerous electrolyte ab¬ the neck, including histological step calcium precipitation is in agreement normalities may go undetected or sectioning. All long bones sampled with previous reports*-"-1 that have their effects may be treated incorrect¬ disclosed considerable cortical thick¬ noted this association in areas of ly. In these cases the ophthalmologist ening and severe medullary stenosis. metastatic calcification in various may make the diagnosis and should be Numerous CNS calcifications were sites of the body. While the pathogen¬ aware of the serious effects of the present within the basal ganglia and esis of mineralization is not well electrolyte and endocrine abnormali¬ dentate nuclei, and focal mineraliza¬ understood, it appears that acid ties. tion was seen in the white matter of mucopolysaccharides serve as a neces¬ Kenny's syndrome bears a superfi¬ the cerebral hemispheres and cerebel- sary matrix during the process of cial resemblance to pseudohypopara- lar folia. calcification. The retinal calcification, thyroidism. Classically, the latter pa¬ The ocular manifestations of these which was detectable only by special tients tend to be mentally retarded, calcium abnormalities are of interest. histochemical stains, appears to be are stocky, disproportionate dwarfs, Patient 1 exhibited bilateral band unique and was not noted in the case and lack the characteristic roentgeno- keratopathy. Patient 4 showed an reported by Berkow et al.20 We have graphic picture of the long bones seen unusual pattern of corneal calcifica¬ no explanation for its heavy concen¬ in Kenny's syndrome. However, as tion that was not visualized on clinical tration within the inner retina, partic¬ this condition becomes better defined, examination or in the routine hema¬ ularly within the cytoplasm of Müller it may well be classified as a hypo- toxylin-eosin sections, but was detect¬ cells and the nuclei of ganglion cells. parathyroid variant, possibly even able only with the aid of special histo¬ While calcium was present in the coming to represent the prototype of chemical stains for calcium. In band vascularized portion of the retina, it is congenital hypoparathyroidism. keratopathy occurring in patients of interest to note that retinal vessels with no abnormalities of blood cal- were practically devoid of detectable

References

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