Electroretinography in incontinentia pigmenti

Electroretinography in Incontinentia Pigmenti Rosane C. Ferreira, MD, ~b,¢Caroline Shea, MD, b,~David W. Johnson, MD, c and J. Bronwyn Bateman, M D b,c

i

ncontinentia pigmenti is a rare ectodermal dysplasia characterized by infantile skin lesions and frequent association with dental, skeletal, and central nervous system anomalies. ~,2It is an X-linked dominant disease with lethality in most male embryos. 1,2 It was first described by Garrod 3 in 1906 and later named Bloch-Sulzberger syndrome.4,sThe gene has been mapped to the pl 1 band of the X chromosome.6 The name incontinentia pigmenti describes the characteristic, although nonspecific, histologic feature in which there is incontinence of melanin from the melanocytes in the basal layer of the epidermis into the superficial dermis. Stage 1 lesions develop in approximately 90% of affected patients and are characterized by a vesiculobullous inflammatory reaction randomly dispersed on the extremities and trtmk. Stage 2 verrncous lesions often are overlooked before the onset of stage 3 hyperpigmented whorls and streaks. As stage 3 lesions fade in childhood years, stage 4 atrophic hypopigmented patches and streaks may emerge. 1,2'7 Approximately one third of cases of incontinentia pigmenti have ophthalmologic manifestations? Infantile retinal detachment, cataract, optic atrophy, blue sclera, strabismus, and nystagmus have been described.2,8 Other reported ophthalmologic manifestations associated with incontinentia pigrnenti include congenital retinal fold and retinal dysplasia, retinal pigment epitheliopathy, retinal vasculopathy, exudative chorioretinitis, conjunctival pigmentation, and nasolacrimal duct obstruction.2,8 We describe abnormal electroretinographic (ERG) and ocular findings in a child with incontinentia pigmenti.

FIG. 1. Fundus photograph of right eye exhibiting hypoplastic macula with anomalous vein traversing inferior fovea area.

CASE R E P O R T Diagnosis of incontinentia pigmenti in a 13-month-old girl was made at birth. She was born with an erythematous

From the Depa~tment of Ophthalmology, Federal University of S~o Paulo, Brazil'; Depa~¢merit of Ophthalmology, The Children's Hospital, University of Colorado, Denverb; and t,~e DeparmLent of Ophthalmology, University Hospital, University of Colorado Health Sciences Center, Denver.~ J AAPOS 1997;1:172-4. Reprint requests:J. Bronwyn Bateman, MD, Universi(y of Colorado Health SciencesCenter, Deparmzent of Ophthalmology, 4200 E. Ninth Ave., B204, Denver, CO 80262. Copyright © 1997 by theAm~qcan Asso~tionf~" Pediaq4c Ophthalmologyand Strabisnucs. I091-8Y31/97 5Y.O0 + 0 75/1/80304

1 72 September 1997

FIG. 2, B-scan ultrasound of left eye demonstrating funnel retinal detachment.

vesicular rash covering her face, scalp, trunk, and extremities. Her mother and maternal grandmother are similarly affected. Her maternal grandmother had nine pregnancies: four male losses around 20 weeks' gestation, two healthy Journal of AAPOS

Journal of AAPOS Volume 1 Number 3 September 1997

Ferreira et al.

4

4 [,

+,ltlllalllr,t 8

ms

173

[,,,,l+,,,l~,,ll,,llliJJJl,l,,l,+l,I, p e r Dlv:l s

tc,

uV/div

[l,+:ltter,l,l~Jl,l,Jl,+,ele,e,!,,+,!+,*~!t~++l~+,,Ir ~ mm [,er I) l v l ~

n

I¢)n

FIR. 3. ER6 of right eye demonstrating rod-isolated waveform with -25 dg and 0 dB single flash. Note

decreased b-wave amplitude.

4

zJ

51 dRiv

.... ~

~

uLJ/liv

1.,4

r I ~ I

I I I I

I I i I

ms

t I f I

i l n a l t l l l l ~ n , ~ l l a n n l n l t n l l l l n l l

p ~ r

I)

1 v

i .~-~ I ~ l n

inlt

IJlriFellell~

8

, n l n l n l l l l l i F l l l

ms

p~r"

Di

v

*llllel~rzn},l

! s

,lla

| 4r~,n

FIG. 4. ERE of right eye demonstrating dark-adapted bright flash waveform and photopic waveform. Implicit times and amplitude are abnormal.

sons, and three affected daughters. The patient had undergone evaluation at another institution, which included a visual evoked response, and her mother was told of a "folded" retina in one eye. At the time of presentation, her vision was central and maintained OD at near only and she had no fixation OS with significant objection to occlusion OD. She exhibited fine horizontal nystagmus. Fundus examination revealed a possible retinal detachment OS. She was taken to the operating room and was examined under anesthesia. Intraocular pressure measured 15 mm Hg OD and 4 mm Hg OS soon after induction. Anterior segment examination of the right eye was unremarkable and notable for a shallow anterior chamber with posterior synechiae formation in the left eye. Posterior segment examination showed a slightly pale optic nerve and a hypoplastic macula without a foveal depression OD; an anomalous retinal vein traversed the inferior foveal area. Both arterioles and venules were slightly tortuous (Figure 1). In zone 2 near the equator of the right

eye, the normal vasculamre terminated and the remaining periphery was avascular. Superotemporally OD, neovascular tissue extended for 2 clock hours and appeared inactive. Some slight traction also appeared superiorly along a major retinal venule. Posterior examination of the left eye revealed a dear lens with retrolenticular fibrovascular membrane preventing a view of the fimdus. With the patient under anesthesia, nltrasonography of the left eye delineated a fimnel retinal detachment with a closed configuration posteriorly and slightly more open anteriorly (Figure 2). ERG of the right eye was performed after 20 minutes of dark adaptation. The LKC UTAS2000 Kirbishfeld handheld Ganzfeld stimulator (LKC Technologies, Inc., Gaithersburg, Md.) was used with a Burian-Allen bipolar electrode (Hansen Opthalmic Development Laboratories, Iowa City, Iowa). Computeraveraged responses demonstrated markedly diminished photopic and scotopic responses; the photopic was affected to a greater extent (Figures 3 to 5). Oscillatory

174

Journal ofAAPOS Volume 1 Number 3 September 1997

Ferreira et al.

5 mimuteslilkt =411pt~l

4 N @Riv

0Utliv

k~i tmb

12,3

,iJllJiiJIiiIiIJ,,ll,,,lllllllll~lllll~llJl,llllllJ 5

m~

p~

r

D

I ~

I ~

.-~

I o

m.~

>l[- r

I) i v

i ~

| ()rl

FIG. 5. ERG of right eye showing photopic response after 5 minutes of light adaptation with little change in waveform. Last part of ERG shows flicker response to 30 Hz with no identifiable waveforms.

potentials were recordable with minimal a-wave and bwave development. T h e flicker response to 30 H z was markedly subnormal as well (Figure 5).

DISCUSSION Since Bloch 4published the syndrome in 192 6, more than 600 cases have been reported. 7,9 In 1976, C a r n e y 9 reviewed the published descriptions of 653 patients and found that nearly 80% of the individuals had at least one associated systemic manifestation. Subsequent reports confirm the involvement of bones, breast, hair, nails, and soft tissues. ],2,8,1°,]1 Skin lesions are characteristic and present in almost 100% of the patients. Dental abnormalities occur in 65% of patients and are identifiable by the age of 2 y e a r s . 9 T h e central nervous system is affected in up to 33% of patients12; the most commonlyreported abnormalities include seizures (13 %), mental retard ation ( 12 %), and spastic paralysis ( 11% ). 9 Ophthalmologic manifestations have been reported in 25% to 35% of patients; strabismus is the most c o m m o n (18%). 2'12'13 Retinal detachment is the most frequent intraocular abnormality. 13-16Asymmetric eye involvement is usual, and the affected eye may be microphthalmic. 14 O u r patient had a retinal fold in her left eye, and subsequently a retinal detachment developed. She exhibited mild optic atrophy and macular hypoplasia with a peripheral avascular retina in the other eye. Our patient's E R G result was markedly abnormal. T h e decreased flicker and photopic response may be explained by the hypoplasia of the macula, and the diminished scotopic response may be correlated with the avascularity of the peripheral retina. T h e photopic responses were more depressed, and we concur that the cones are more affected than the rods in this patient. Although retinal changes are prominent in this disease, E R G s have not been reported previously. W e describe the E R G findings in incontinentia pigmenti. Both the a-wave

and b-wave had decreased amplitudes, and an increase was noted in the b-wave implicit time. T h e child had a retinal detachment in one eye and macular aplasia in the other. In conclusion, the E R G may be abnormal in incontinentia pigmenti.

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

References Landy SJ, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger syndrome).J Med Genet 1993;30:53-9. Goldberg MF, Custis PH. Retinal and other manifestations of incontinentia pigmenti (Bloch-Sulzberger syndrome). Ophthalmol 1993;100:1645-54. Garrod AE. Peculiarpigmentationofthe skin of an infant. Trans Clin Soc Lond 1906;39:2116. Bl°chB' Eigent/imliche'bisher nicht beschriebenePigrnentaffekti°n (Incontinentia Pi.grn.end). SchweizMed Wochenschr 1926;7:404-5. Sulzberger MD. Uber eine bisher nicht beschriebene congenitale Pigmentanomalie (Incontinentia Pigmenti). Arch Dermatol Syph (Berlin) 1928;154:19-32. Cannizzarro LA, Heckt F. Gene for incontinentia pigmenti maps to band Xpll with an (X:10)(P112) translocation. Clin Genet 1987;32:66-9. Cohen PR, GarciaJ. Pathological cases of the month: incontinentia pigmenti. Arch Pediatr AdolescMed 1994;148:531-2. Smith B, Bedrossian EH. Incontinentia pigmenti associated with nasolacrimal duct obstruction. Ophthalmol Surg 1984;15:980-2. Carney RG Jr. Incontinentia pigmenti: a world statistical analysis. Arch Dermatol 1976;112:535-42. Sahn EE, Davidson LS. Incontinentia pigmenti: three cases with unusual features.J Am Acad Dermatol 1994;31:852-7. Pellegrino RJ, Shah AJ. Vascular occlusion associated with incontinentia pigmenti. Ped Nenrol 1994;10:73-4. Cohen BA. Incontinentia pigmenti. Neurol Clin 1987;5:61-77. Heathcote JG, Schoales BA, Willis NR. Incontinentia pigmenti (Bloch-Sulzbergersyndrome): a case report and review of the ocular pathological features. CanJ Ophthalmol 1991;26:229-37. Catalano RA. Incontinentia pigmenti. Am J Ophthalmol 1990;110:696-9. Wald KJ, Mehta MC, Katsumi O, et al. Retinal detachments in incontinentia pigmenti. Arch Ophthalmol 1993;111:614-7. McCralT JA, Smith L. Conjunctival and retinal incontinentia pigmenti. Arch Ophthalmol 1968;79:417-22.