A C T A O P H T H A L M O L O G I C A 61 (1983) 313-321

Departments of Ophthalmology' (Head: S . M . Podos), Pediatric? (Head: K . Hirschhorn), and

Pharmacology3 (Head: J . P . Green) of the Mount Sinai School of Medicine, New York, NV, USA

DIFFUSE CHOROIDAL ATROPHY AND KLINEFELTER SYNDROME

MURRAY A. WOLKSTEIN', ADAM K. ATKIN',

JUDITH P. WILLNEW and JOEL S. MINDEL113

We report the first case of diffuse choroidal atrophy associated with Klinefelter syndrome. Retinal findings included midperipheral bone corpuscular pigmentation, large areas suggestive of choroidal atrophy, and unusual golden crystalline structures that apparently were mainly in the neurosensory retina. A sensorineural hearing deficit was also noted. Biochemical studies, including amino acid blood levels, were within normal limits. This case is of interest because of the rarity of association between Klinefilter syndrome and retinal or, in fact, any ocular abnormalities.

Key words: Klinefelter syndrome - choroidal atrophy - fluorescein angiography .

Klinefelter syndrome was first described in 1942 as a disorder in males of unknown pathophysiology, consisting of gynaecomastia, azoospermia, and elevated urinary gonadotrophins (Klinefelter et al. 1942). Bradbury et al. (1956) reported the presence of sex chromatin or Barr bodies in the cells of the buccal mucosa of these patients and proposed that an X-chromosome abnormality existed. Subsequent chromosome counts confirmed that these phenotypic males did have an extra X chromosome, giving them a 47,XXY chromosomal complement. Less common variants are the 46,XY/47,XXY Klinefelter mosaics (Paulsen et al. 1968). Ocular

Received on June 29th. 1982.

3 13

Wolkstein et al. Choroidal atrophy and Klinefelter

abnormalities, especially retinal disorders, are uncommon in Klinefelter syndrome (Duke-Elder 1976). We present herein the first reported case of diffuse choroidal atrophy associated with Klinefelter syndrome.

Case Report

The patient was a 47-year-old male of Italian descent who complained of a ‘recent’ history of bilateral progressive visual loss associated with headache and ‘colored rainbows’ in his central field of vision. He was admitted to the Neurology Service of the Mount Sinai Hospital to rule out a pituitary tumour because of suspicious bitemporal loss on confrontation field testing.

Twenty-one months prior to the admission, the patient had been diagnosed elsewhere as having glaucomatous visual field loss in the right eye, and filtering surgery had been performed for presumed low tension glaucoma. His past medical history also revealed that at age 31 the patient had ligation of his vena cava for phlebitis and pulmonary emboli. The family history revealed the patient to be the youngest of 7 siblings, 4 males and 3 females. His mother was 52-years-old at the time of his birth. One sister, the oldest, had died, and was said to have had a ‘rare’ disease and cataracts. The remainder of the family history was negative for ocular disease. The patient had no children from either of 2 marriages. On review of systems, the patient reported bilateral hearing loss, which had seemed to progress recently. In addition, he claimed that he never had to shave more than once a week, but denied decreased libido, impotence, or ejaculatory failure.

Physical examination revealed a 185 cm (6’1”), moderately obese male weighing 115 kg (254 pounds) with gynaecomastia, decreased facial, chest, and pubic hair, and firm small testes (less than 2 cm in diameter). There was pitting oedema and tenderness of both lower extremities. Aside from the visual field abnormalities, the neurologic examination was normal.

Routine studies including blood count, serum chemistries, urinalysis, chest and skull X-rays, and electrocardiogram, were normal. In addition, an electro- encephalogram, brain scan, and computerized axial tomography of the head were all within normal limits. An audiogram revealed a sensorineural hearing loss in each ear.

Ophthalmologic evaluation was requested. The patient was a secretive and evasive historian, but on careful questioning he admitted to difficulty seeing in dim lighting.

Corrected visual acuity was 201200 OD ’and 20160 0s. A filtering bleb and a sector iridectomy were present OD. The external examination and anterior segments were otherwise normal, and the media were clear. Pupillary reflexes were intact. Goldmann applanation tonometry gave values of 16 mmHg, OD and 0s.

3 14

Wolkstein et al. Choroidal atrophy and Klinefelter

The posterior vitreous was detached in each eye. Retinal examination revealed clumps of intraretinal pigment in the midperiphery of each eye, and large areas suggestive of choroidal atrophy, with whitish appearing large choroidal vessels (Fig. 1). Golden crystalline spots were scattered over the posterior pole. On Goldmann

Fig. 1. Diffuse choroidal atrophy. Golden crystalline spots are scattered over the posterior pole.

Midperipheral pigmented bone spicules are also present.

3 15

Wolkstein et at. Choroidal atrophy and Klinefelter

LEFT RIGHT Fig. 2.

Goldmann fields showing dense ring scotomata and peripheral constriction.

I . 'g. 3. (a and b) Early-phase fluorescein aiigiograms demonstrating widespread choriocapillaris non-perfusion with small intact islands ofchoriocapillaris. (c) Late-phase staining of choroidal

and scleral collagen.

Wolkstein et al. Choroidal atrophy and Klinefelter

contact lens examination, the golden deposits seemed to be located at variable depths in the neurosensory retina and also at the level of the pigment epithelium. The optic discs and vessels were normal in appearance.

Psychophysical and electrophysiologic test results follow. The patient was not able to see any of the AOHRR colour figures. The Farnsworth D- 15 panel gave a tritan axis of confusion OD and a normal pattern 0s. Goldmann field testing demonstrated a broad dense ring scotoma and peripheral field constriction O U (Fig. 2). Dark adaptometry profiles revealed elevated cone and rod thresholds in each eye. The electroretinogram was markedly subnormal under both light and dark adapted testing conditions. Two years later, his corrected visual acuity had declined to 201400 OD and 20180 OS, his visual fields were markedly reduced, and the electroretinogram and flash visually evoked responses were extinguished.

Fluorescein angiography, performed in order to differentiate between diffuse choroidal atrophy and retinitis pigmentosa, confirmed the diagnosis of diffuse choroidal atrophy (Fig. 3). Large areas of choriocapillaris non-perfusion were demonstrated throughout the fundi OU with occasional small islands of intact choriocapillaris. The large choroidal vessels, not normally noted angiographically, were observable on the angiogram photographs. In contrast, patients with retinitis pigmentosa typically show marked background hyperfluorescence throughout the fundus due to generalized pigment epithelial atrophy, but show the underlying choriocapillaris mostly intact.

N o fluorescein abnormalities were noted corresponding with the position of the previously described golden crystalline-like spots. Amino acid assays of plasma and urine were normal.

A genetic evaluation gave the following results. Dermatoglyphics showed a low total finger ridge count for a male. A buccal smear revealed the presence of a single Barr body in 2 4 out of 100 cells. Chromosome studies on cultured peripheral lymphocytes revealed a 47,XXY complement in all 20 cells examined. Banding studies (Fig. 4), using the quinicrine mustard fluorescence method, showed normal banding of all chromosomes. The extra C-group chromosome was an X, substantiating the diagnosis of Klinefelter syndrome.

Discussion

The case illustrates the importance of a comprehensive evaluation in the differen- tial diagnosis of conditions affecting the visual system. The patient underwent glaucoma filtering surgery in one eye and an extensive neurologic evaluation before the correct diagnosis was entertained. The nyctalopia, ring scotoma on visual field

3 18

Wolkstein et al. Choroidal atrophy and Klinefelter

Fig. 4. Q-banded (quinicrine mustard method) metaphase preparation from a cultured peripheral lymphocyte shows normal banding of all chromosomes. Karyotype is 47,XXY, and extra

C-group chromosome is an X.

testing, and funduscopic findings pointed to a progressive retinal or choroidal dystrophy. The patient’s eunuchoid appearance, decreased body hair, and atrophic testes suggested hypogonadism and the possibility of a chromosomal abnormality. This led to the genetic evaluation and confirmation of Klinefelter syndrome.

Ocular abnormalities are uncommon in Klinefelter syndrome (Duke-Elder 1976). Uveal colobomata (Francois et al. 1970; Hashmi & Karseras 1976), bilateral anophthalmos (Wetter et al. 1974), and unilateral corneal opacities (Boreaux et al. 1969) have been reported. Mild lens opacities have been described in patients who have both Klinefelter syndrome and myotonic dystrophy (Sparkes et al. 1973; Fiol et al. 1975). Nowakowski et al. (1958) reported 3 of 34 Klinefelter patients with some form of colour blindness. ’In contrast, Polani et al. (1958) reported no cases of colour blindness in 55 patients with Klinefelter syndrome.

T o our knowledge, there are no case reports of diffuse choroidal atrophy associated with Klinefelter syndrome in the literature. Only 2 cases of an association

,

3 19

Choroidal atrophy and Klinefelter Wolkstein et al.

with retinitis pigmentosa have been reported (Nowakowski 196 1 ; Molnar 1970). One of these cases was not confirmed with electroretinography (Nowakowski 196 I), and is therefore open to question. The second case had electrophysiologic studies, but fluorescein angiography was not performed (Molnar 1970). In our laboratory, we have seen a number of cases of diffuse choroidal atrophy which were referred with a presumed diagnosis of retinitis pigmentosa. Diffuse choroidal atrophy is occasionally confused with retinitis pigmentosa because nightblindness, ring scotomata, extinguished ERG, and bone corpuscular pigmentation may occur in either condition. Fluorescein angiography is sometimes necessary for differentiating these 2 conditions.

An unusual retinal finding in this patient was the presence of golden crystalline deposits at variable depths in the neurosensory retina. Intraretinal crystalline bodies have been reported in a number of syndromes such as Sjogren-Larsson syndrome (Gilbert et al. 1968), Bietti’s tapetoretinal degeneration with marginal corneal dystrophy (Bagolini & Ioli-Spada 1968), primary oxyluria (Gass 1977), oxalosis in cases of renal failure after methoxyflurane anaesthesia (Gass 1977), etc. In the present case, we were not able to explain the nature of the golden crystalline bodies. There were no corresponding fluorescein angiographic abnormalities. Moreover, plasma and urine amino acid assays were normal.

Since the only previous reports we found of retinal abnormalities associated with Klinefelter syndrome were 2 cases of retinitis pigmentosa (Nowakowski 196 1 ; Molnar 1970), the finding of generalized choroidal atrophy in such a patient was interesting. The patient also suffered from bilateral sensorineural hearing loss, which has sometimes been found in association with retinitis pigmentosa (Krill 1977), but never, to our knowledge, with either Klinefelter syndrome or choroidal atrophies.

References

Bagolini B & Ioli-Spada G (1968): Bietti’s tapetoretinal degradation with marginal corneal dystrophy. Am J Ophthalmol65: 53-60.

Boreaux G, Tajmirova 0, Klein D, Gauthier G & Felgenhauer W R (1969): Deux cas de syndrome de Klinefelter en mosaique (46,XY/47, XXY) dont I’un associe a une protanopie et I’autre a des opacites corneennes unilaterales. Arch Julius Klaus-Stiftung Vrerbungs- forsch, Sozialanthropologie Rassenhygiene 44: 55-64.

Bradhury J T, Bunge R G & Boccahella R A (1956): Chromatin test in Klinefelter’s syndrome (Letter to the editor) J Clin Endocrinol Metab 19: 689.

Duke-Elder S (1976): System of Ophthalmology. Vol. XV. Summary of Systemic Ophthalmology, p 37. C. V. Moshy Co., St. Louis.

Fiol M E, Daly R F & Osborne R H (1975): Dystrophia myotonia in a 47,XXY male. Neurology 25 : 472 -476.

320

Wolkstein et al. Choroidal atrophy and Klinefelter

Francois J, Matlon-van Leuven M T & Gombault P (1970): Uveal coloboma and true Klinefelter’s syndrome. J Med Genet 7: 2 13-223.

Gass J D M (1977): Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment (2nd edn), p 208. C. V. Mosby Co., St. Louis.

Gilbert W R, Smith J L & Nyhan W L (1968): The Sjogren-Larsson syndrome. Arch Ophthalmol80: 308-316.

Hashmi M S & Karseras A G (1976): Uveal colobomata and Klinefelter syndrome. Br J Ophthalmol60: 661-664.

Klinefelter H F Jr, Reifenstein E C J r & Albright F (1942): Syndrome characterized by gynecomastia, aspermatogenesis without a-laydigism, and increased excretion of follicle- stimulating hormone. J Clin Endocrinol Metab 2: 615-627.

Krill A E (1977): Krill’s Herditary Retinal and Choroidal Diseases. Vol. 11. Clinical Characteristics p 533. Harper & Row, New York.

Molnar L ( 1970) : Gleichzeitiges Vorkommen von Klinefelter-Syndrom und Degeneratio Pigmentosa Retinae. Klin Monatsbl Augenheilkd 157: 663-667.

Nowakowski H (1961): Neuere Erkentnisse uber das Klinefelter Syndrom. Arch Klin Dermatol213: 765-769.

Nowakowski H, Lenz W & Parada J (1958): Diskrepanz zwischen Chromatinbefund und chromosomalem geschlecht beim Klinefelter syndrom. Klin Wocbenschr 36: 683-684.

Paulsen C A, Gordon D L & Carpenter R W (1968): Klinefelter’s syndrome and its variants: a hormonal and chromosomal study. Rec Progr Horm Res 24: 32 1-363.

Polani P E, Bishop P M F, Lennox B, Ferguson-Smith M A, Stewart J S S & Prader A (1958): Colour vision studies and the X-chromosome constitution of patients with Klinefelter’s syndrome. Nature 182: 1092- 1093.

Sparkes R S, Samec L, Kaplan S A & Coulson W F (1973): Concurrence of myotonic dystrophy and XXY Klinefelter syndrome. Clin Genet 4: 264-269.

Welter D A, Lewis L W, Scharff L & Smith W S (1974): Klinefelter’s syndrome with anophthalmos. Am J Ophthalmol77: 895-898.

Author’s addre.c.c:

Murray Wolkstein, M.D., Department of Ophthalmology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029 USA.

32 1 ? I