Hypopigmented Iris Spot

An Early Sign of Tuberous Sclerosis

ISAAC GUTMAN, MD, DAVID DUNN, MD, MYLES BEHRENS, MD, ARNOLD P. GOLD, MD, JEFFREY ODEL, MD, MARCELO R. OLARTE, MD

Abstract: Hypopigmented skin spots, resembling the mountain ash leaf, may represent the earliest sign in tuberous sclerosis. We examined two patients with hypopigmented iris spots who suffered from this sys­temic disease. These iris spots may be analogous to the skin lesions, which have decreased amount of melanin in the melanosomes. [Key words: hypopigmented iris spots, melanin, skin hypopigmentation, tuberous sclerosis.] Ophthalmology 89: 1155-1159, 1982

Tuberous sclerosis is a heredofamilial disease characterized by a triad of mental deficiency, epilepsy, and adenoma sebaceum. 1 Hamartomatous lesions in­volving various organ systems have been described. The central nervous system, viscera, skin, and the eyes are involved most commonly. 2 Hypopigmented spots on the skin, resembling the ash leaf, were described by Gold and Freeman. These spots may represent the earliest sign of tuberous sclerosis. 3 Hy­popigmented spot(s) on the iris, recently described, may also be an early sign in this disease. 4 ,5 In two additional cases of tuberous sclerosis, hypopigmented spots on the iris were noted. Their detection may be of value in early diagnosis.

CASE REPORTS

Case 1. A I4-month-old boy was evaluated for a seizure disorder. A normal delivery had followed an uncomplicated 8!1-month gestation. The neonatal period was normal. De­velopment thereafter was delayed. The child smiled at 8

From the Departments of Ophthalmology, Neurology and Child Neurology, Columbia-Presbyterian Medical Center, New York, New York.

Drs. Gutman and Odel are Fellows in Neuroophthalmology, spon­sored by the Nate B. and Frances Spingold Foundation, Inc., New York, New York.

Reprint requests to Isaac Gutman, MD, 345 E. 69th Street, New York, NY 10021.

0161-6420/82/1000/11551$1.05 © American Academy of Ophthalmology

weeks, rolled over at 8 months, sat alone at II months, and pulled to standing by 12-13 months. He was unable to walk unassisted. He started to talk (one to two words) at 14 months but played no games. There was no family history of neurologic problems. His father (age 29) and mother (age 28) were healthy. A 4-year-old brother and a 3-year-old sister were examined and were found to be healthy and normally developed.

On initial examination the head circumference was 44 cm «3%) and the weight 8.6 kg «3%). Three small oval hypopigmented macules were present on the trunk. A prominent whitish spot was seen in an otherwise normal­looking iris in the right eye (Fig 1). Dilated fundus examina­tion was negative. Other abnormalities on physical examina­tion were bilateral enlarged kidneys and muscular hypotony with physiologic deep tendon reflexes. An IVP showed bilat­eral polycystic kidneys. CT scan revealed discrete areas of periventricular calcification. A diagnosis of tuberous sclerosis was made.

Case 2. A 28-year-old white woman had a history of sei­zures from 8 years of age that were controlled by primidone. At age II sudden loss of vision in the right eye was attributed to central retinal artery insufficiency. No further details of her ocular examination were available. Arteriography was done at that time and demonstrated a right supraclinoid ca­rotid aneurysm. Recently, she again lost vision acutely in the right eye. Her vision was light perception with marked right relative afferent pupillary defect. Fundoscopy revealed ele­vated disc with irregular borders and markedly narrow ar­teries. After six hours her vision returned to 20130 with mild relative afferent defect. The left eye was normal. The pre­sumptive diagnosis was transient central retinal artery spasm. Her father (age 58) was said to have tuberous sclerosis. The mother (59) had diabetes mellitus. A younger

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OPHTHALMOLOGY • OCTOBER 1982 • VOLUME 89 • NUMBER 10

Fig 1 Hypoplgmented spot on the fight IfIS (case 1)

Fig 2 HYPoplgmented skm lesIOn (ash leaf spot) (case 2)

Fig 3 Two hYPoplgmented spots on the left IfIS (case 2) I.

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GUTMAN, et al • HYPOPIGMENTED IRIS SPOT

sIster wIth epIlepsy dIed at age 16 wIth what was saId to be a renal complIcatIOn of tuberous sclerosIs Another sIster (22) and brother (26) were reported to be m good health None of the famIly members were exammed

PhysIcal examinatIOn revealed a mIldly obese alert female General physical exammatlOn was wIthIn normal lImIts but

Fig 5 NasolabIal fold shows adenoma sebaceum

Fig 4 Fundus photograph of the nght eye (case 2) .

for multIple ash leaf spots on her skm (FIg 2), adenoma sebaceum (FIg 5) and subungual fibromata on the fingers and toes (FIg 6) NeurologIc exammatlOn was unremarkable

The ocular exammatIOn revealed vIsual aCUity of 20/30 In the nght eye and 20120 m the left eye. TensIon by applanatIOn was 16 mm Hg In both eyes The anterIor chamber was deep and clear In each eye There were two hYPoplgmented spots on the superIor one thIrd of the nght IfIS that dId not look atrophIc. dId not retrOlllummate, and had the same structure as the unInvolved IfIS (FIg 3) The antenor chamber angle adjacent to the hypopigmented spots seen by gOOlopnsm was mtact Ins fluorescem angIOgraphy showed no abnormal vessels, early leakage, or late stammg of the lesIOn (FIgs 7. 8) The left 1fI!> was normal The pupIls were 3 mm equal and normally reactIve The nght fundus showed what appeared to be an astrocytIc hamartoma of the dIsc WIth hypoplg­mented area between the dIsc and the macula and mIldly narrow retmal artenes (FIg 4)

DISCUSSION

HYPoplgmented spots may represent the earliest cutaneous sign in tuberous sclerosIs.3 These whIte macules are present m more than 50% of patIents WIth thIs syndrome. Most of these areas of hypopigmenta­hon are present before any other vIsIble lesIOns of tuberous scleroSIS have appeared The vast majority, If not all, of the whIte macules appear at birth.6 Most of these spots have a configuration tYPIcal of a mountain ash leaf and differ m shape from cafe-au-Imt spots, an­other skm lesIOn that occasIOnally can be observed m tuberous sclerosis. 3,6,7 HIstologIcally, there IS a marked reductIOn of the amount of melamn in the melanosomes and an apparent dimmutlOn m their size. 6 The vascularIty of the skm m the hypopigmented areas IS normal The combmation of the white macules and mfantIle spasms IS consIdered pathognomomc of tuberous sclerosIs. 8,9

The two patients reported presented WIth the tYPIcal cutaneous whIte macules of tuberous sclerOSIS and the

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OPHTHALMOLOGY. OCTOBER 1982 • VOLUME 89 • NUMBER 10

FIgs 6A-8 A, left. subungual fibroma. fight mdex finger. B. nght. subungual fibromata, fight foot

]Flg 7 Fluorescem angIOgraphy of the ms (case 2)-early phase lThere are no abnormal vessels and no leakage

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FIg 8 Fluorescem angIography of the ms (case 2)-late phase There IS no leakage or late stammg

GUTMAN, et al - HYPOPIGMENTED IRIS SPOT

more unusual hypopigmented iris lesion(s). In case 1 the iris spot was small and did not look atrophic. In case 2, the spots were larger, occupying the upper third of the iris. The anterior iris stroma appeared by slit lamp to have normal structure, and normal iris ves­sels could be seen traversing the lesion as in the patient reported by Kranias and Romano. 4 Fluorescein angi­ography showed no atrophy, fibrosis, or increased vascularity. Presumably these hypopigmented lesions of the iris are analogous to the cutaneous white macules. It is uncertain whether there is a relationship between the hypopigmented peripapillary lesion in our second patient and the hypo pigmented fundus lesion reported by Lucchese and Goldberg5 and considered analogous to the skin- and iris-hypopigmented lesions associated.

About 25 patients with tuberous sclerosis have been seen by one of the authors (APG) since the first patient was examined (1978). Iris spots were not seen in any of those patients. The true incidence of this recently de­scribed sign is unknown.

In summary, along with ash leaf skin lesions, hypopigmented spot(s) on the iris may be an early visi-

ble sign of tuberous sclerosis. Their detection may alert the physician to the presence of the disease.

REFERENCES

1. Bourneville D. Contribution a I'etude de I'idiotie; idiotie et epi­lepsie hemiplegique. Arch Neurol (Paris) 1880; 1 :69-91.

2. Gomez MR, ed. Tuberous Sclerosis. New York: Raven Press, 1979.

3. Gold AP, Freeman JM. Depigmented nevi: the earliest sign of tuberous sclerosis. Pediatrics 1965; 35: 1 003- 5.

4. Kranias G, Romano PE. Depigmented iris sector in tuberous sclerosis. Am J Ophthalmol 1977; 83:758-9.

5. Lucchese NJ, Goldberg MF. Iris and fundus pigmentary changes in tuberous sclerosis. J Pediatr Ophthalmol Strabis­mus 1981; 18(6):45-6.

6. Fitzpatrick TB, Szabo G, Hori Y, et al. White leaf-shaped macules: earliest visible sign of tuberous sclerosis. Arch Dermatol 1968; 98: 1-6.

7. Chao DH-C. Congenital neurocutaneous syndromes in child­hood. II. Tuberous sclerosis. J Pediatr 1959; 55:447-59.

8. Harris R, Moynahan EJ. Tuberous sclerosis with vitiligo. Br J Dermatol 1966; 78:419- 20.

9. Gold AP. Discussion. Year Book Pediatr 1966-1967: 170-1.

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