British Journal of Ophthalmology, 1987, 71, 629-634

Incontinentia pigmenti (Bloch-Sulzberger syndrome):seven case reports from one familyA SPALLONE

From the St Gerardo Hospital, Department of Ophthalmology, Monza (Milan), Italy

SUMMARY Seven members from a large family who showed signs of incontinentia pigmenti wereexamined. A clear X-linked dominant transmission was demonstrated, lethal in males. Study ofthis family shows that vascular abnormalities of the retina and disorders of the retinal pigmentepithelium are the most important ocular lesions in the Bloch-Sulzberger syndrome.

Incontinentia pigmenti (Bloch-Sulzberger syndrome)is a genetic disease of the skin with generalisedectodermal and mesodermal dysplasia which mayoften involve the eyes (35% of the patients),' hair,teeth, and central nervous system. Skin lesions areCorrespondence to Dr A Spallone.

usually present at birth or shortly after in the form oferythematous eruptions with linear vesiculations.The final stage is characterised by irregular macularstreaks of brown to slate-grey pigmentation, dis-tributed asymmetrically on the torso and sometimeson the limbs.

0: Affected femaleO:Not affected femaleO:Not affected male*:Dead for unknown cause

Fig. 1 Pedigree offamily described.

eCase reports*:ProbandMMiscarriages of unknown sexMgMiscarriages autoptically male

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Fig. 3 Case). Left eye.

We have had the opportunity to study sevenpatients all of whom are members of one large familyin which a total of 14 members were affected byincontinentia pigmenti. A clear X-linked dominanttransmission was demonstrated, lethal in males (Fig.1). The following seven case reports illustrate themost important ocular lesions of the disease.

Case reports

CASE 1This was the proband. A female child, 4 years old,birth weight 3 kg. The parents were not related. Thedermatological symptoms of incontinentia pigmentiappeared immediately after birth.

Ocular examination showed nystagmus, oedema-tous cornea, and cataract (Fig. 2) in the right eye,microphthalmus with iridolenticular synechiae andcomplete cataract in the left eye. In this eye the iriswas atrophic, with pigment irregularities (Fig. 3).

Fig. 4 Case). Classic whorls and streaks ofpigmentontorso and in right eye.

Visual acuity was no perception of light in both eyes.Ultrasonography revealed the presence of bilateralretinal detachment with dense membranes in thevitreous. A general medical examination showed theclassic whorls and streaks of pigment on the torso andon the right leg (Fig. 4). The grandmother had had18 pregnancies, 11 of which had been miscarriages.The seven fullterm pregnancies were all resulted infemales. Five of these had ocular and dermatologicalproblems; one died of an unknown cause, and the lastone was healthy. The first of these five affectedpatients is the mother of our proband.

CASE 2Mother of the proband, 37 years old, who has beenaffected by incontinentia pigmenti since birth.

Ocular examination showed intermittent ex-otropia. The visual acuity was 1-0 in both eyes. Bothlenses were clear. In the ocular fundus in the right eyeno anomalies could be found; by contrast in the lefteye the retinal vessels were anomalous. Towards thetemporal equator both venules and arterioles becametortuous, slightly kinked, of an irregular calibre,increased in number, and with preretinal fibrosis.Apart from this area the peripheral temporal part ofthe retina was completely avascular (Fig. 5). In theinferior nasal area there were small alterations of theretinal pigment epithelium. On general medicalexamination we noted some pigmentary alterationsof the skin, the absence of the lateral upper incisors,and a conical appearance of the other teeth. Thepatient had had nine pregnancies; five of these hadended in miscarriages, two of which during necropsywere found to be males.

CASE 3Sister of the proband, 14 years old. Immediately afterbirth the patient developed the dermatological signsof incontinentia pigmenti.

Fig. 2 Case 1. Righteye.

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Fig. 5 Case2. Fluorescein angiogram ofleft eye. In thetemporal equator the retinal vessels are tortuous, slightlykinked, and increased in number. Theperipheral temporalpart ofthe retina is completely avascular.

Ophthalmological examination showed nystagmusand marked exotropia in the left eye. Visual acuitywas 07 in the right eye and counting fingers in the lefteye. The cornea and lens were both clear. The fundusin the right eye was normal. At the temporal equator

Fig. 6 Case 3. Fluorescein angiogram ofthe left eye,showing abnormal vascularisation oftemporalperipheralretina.

Fig. 7 Case 6. Fundus ofright eye: alteration ofpigmentepithelium and choriocapillaris with sharp edges.

of the left eye the vessels arborised and connected inthe form of an arteriovenous anastomosis, withpreretinal fibrosis (Fig. 6). From this equatorial zoneof abnormal vascularisation to the ora serrata theperipheral temporal part of the retina was avascular.In the sector inferior to the optic disc a small defect ofthe pigment epithelium was present.

This patient suffered from epilepsy and had spasticparalysis. In addition one half of the body was notedto be shorter than the other.

CASE 4

Sister of the proband, 10 years old. Incontinentiapigmenti from birth.At the age of 3 months leucokoria was diagnosed in

the right eye. This eye was enucleated because ofsuspected retinoblastoma. Visual acuity in the lefteye as 0-8 with -3 sph. The ocular fundus in the lefteye showed vascular abnormalities in the equatorialretina very similar to that of case 2. The peripheraltemporal part of the retina was avascular. The typicalpigmentary alterations of the skin were observed;dentition was incomplete, and some teeth wereconical.

CASE 5Sister of the proband, 8 years old, incontinentiapigmenti from birth. The anterior segment of theeyes was normal. Visual acuity was 0-6 in the righteye and 0.5 in the left eye. It was not possible toobserve the ocular fundus in this patient.

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Fig. 8 Case 6. Fluorescein angiogram ofright eye: in the Fig. 10 Case 6. Fluorescein angiogram ofleft eye. Belowtemporalperiphery a circular alteration ofthepigment the large atrophic area ofthepigment epithelium aresmallepithelium and choriocapillaris is present. alterations ofthe retinal vascularisation.

CASE 6Aunt of the proband, 34 years old. Vesicular lesionsand hyperpigmentation of the skin occurred two daysafter birth.The right eye was exotropic. The visual acuity was

0-2 in the right eye with -3 75 sph and 0-8 in the lefteye with -8 sph. The corneas and lenses were both

Fig. 9 Case 6. Fundus ofleft eye showing enormousatrophy ofthepigment epithelium in the temporal quadrant.

clear. Temporally to the macula a clearly definedchange in the pigment epithelium and choriocapillariswith sharp edges was present (Fig. 7). In the temporalperiphery another circular alteration of the pigmentepithelium and choriocapillaris was visible (Fig. 8).This zone also showed mild anomalies of the retinalvascularisation. In the left eye it was possible to seea large region of atrophy of the pigment epitheliumwith sharp edges; it involved the whole temporalquadrant (Fig. 9). Just below this large area anothersmall alteration of the retinal vascularisation wasseen (Fig. 10). Apart from these changes, two othersmall atrophic patches were present. Toxoplasmosiswas excluded by blood examinations. She had alo-pecia and abnormal teeth. The lateral incisors weremissing (Fig. 11).

CASE 7Daughter of case 6, 11 years old. Incontinentiapigmenti from birth.

Tilting of the head and strabismus in the righteye were noted at the age of 3 months. Cataractwith retinal detachment were also diagnosed in thiseye. Ophthalmological examination showed a blindmicrophthalmic right eye with cataract (Fig. 12).Ultrasonography revealed the presence of retinaldetachment with dense membranes in the vitreous.Visual acuity was 1-0 with -1-50 sph in the left eye.In this eye the cornea and lens were both clear.The ocular fundus showed only a -small patch ofpigment epithelium atrophy without alteration of the

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Fig. 11 Case6. Abnormal configuration oftheteeth.

retinal circulation (Fig. 13). She had marked dentalanomalies, alopecia, and the typical streaks of pig-ment on the torso.

Discussion

The term incontinentia pigmenti was first used byBloch2 in 1926, when during a histological examin-ation he observed abnormalities of the pigment cellsof the epithelium of the skin, which were thought tobe 'incontinent' of melanin. In 1938 Sulzberger3found other ectodermal defects in association withthis condition. In 1954 Franceshetti and Jadassohn4divided the disorder into two types: the classicincontinentia pigmenti or Bloch-Sulzberger variety,

Fig. 12 Case 7. Microphthalmicrighteye with complicatedcataract.

Fig. 13 Case 7. Fluorescein angiogram ofleft eye: smallpatch ofpigment epithelium atrophy in theperipheral retinaispresent.

which occurs almost exclusively in females, and theNaegli type (or reticular) with a dominant mode oftransmission, which involves both sexes withoutocular malformations.Our family clearly belongs to the Bloch-Sulzberger

variety, and it is certainly the largest family everdescribed. Ocular abnormalities are generally foundin 35% of the cases, and they probably representthe most severe systemic anomalies associated withincontinentia pigmenti. Our patients confirm this lastpoint, and they illustrate the whole range of ocularlesions. One patient (case 4) underwent enucleationat 6 months of age because of suspected retino-blastoma. Ourproband was completely blind. Myopiawas present in three patients, strabismus withamblyopia in five, and cataract in three. It is interest-ing to note that cataracts were present only in thecases with retinal detachment, and theywere probablycaused by the retinal detachment. Microphthalmuswas present in three cases, nystagmus in two. Ophthal-moscopically it was possible to see retinal abnor-malities in four patients. In two other cases a densecataract did not permit us to observe the fundus,but ultrasonography showed abnormalities of thevitreous, retinal detachment, and thickening of thechoroid.

In three of our cases, characteristic and wellmarked changes in the retinal pigment epitheliumand choriocapillaris were visible during ophthal-moscopy as of large plaques, which are probablyanalogous to those observed on the skin. No history

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of trauma, retinal detachment, or toxoplasmosiswas obtained.5 In two patients these changes werebilateral, and in case 6 they were visible, covering allthe temporal quadrant in the left eye. Previously onlyfour papers have reported alterations of the retinalpigment epithelium in incontinentia pigmenti.69However, those alterations were limited, did notcover a wide area, and were less serious than ours.

In addition to pigment epithelium the retinalvascularisation can be seriously affected. We ob-served retinal vessels were sharply interrupted in thetemporal quadrant, with an arteriovenous shunt;they were tortuous and irregular in calibre, withoutsigns of occlusion. From this zone to the ora serratathe retina was completely avascular. One can assumethat the temporal retina had failed to develop,producing areas of capillary non-perfusion with pre-retinal fibrosis. Contraction of this preretinal fibrotictissue results in retinal detachment and multipleconvoluted infoldings of the retina resembling retinaldysplasia, retinopathy of prematurity, posteriorhyperplastic primary vitreous, and other disorders.The retinal vascular abnormalities and the dis-

orders of pigment epithelium are the most importantocular lesions in incontinentia pigmenti. Someauthors8" have inferred a relation between retinalpigment epithelium anomalies and fibrovascularchanges. However, our findings showed that thisrelationship is not so clear. In fact in case 6 therewas a noticeable alteration of the retinal pigmentepithelium and few vascular defects. By contrast incases 2 and 3 we noted serious defects of the retinal

vessels and few alterations in the retinal pigmentepithelium. The anomalies of the retinal vessels andretinal pigment epithelium may perhaps representindependent alterations in the development ofthe retinal vascularisation and the retinal pigmentepithelium, and not necessarily be related.

References

1 Carney RG. Incontinentia pigmenti: a world statistical analysis.Arch Dermatol 1976; 112: 535-42.

2 Bloch B. Eigentumilche, bisher nicht beschriebene Pigmen-taffektion (incontinentia pigmenti). Schweiz Med Wochenschr1926; 56: 404-5.

3 Sulzberger MB. Incontinentia pigmenti (Bloch-Sulzberger);report of an additional case, with comment on possible relationto a new syndrome of familial and congenital anomalies. ArchDermatol 1938; 38: 57-9.

4 Franceschetti A, Jadassohn W. A propos de l'incontinentiapigmenti, delimitation de deux syndromes differents figurantsous le meme terme. Dermatologica 1954; 108: 1-28.

5 Jensen VA. Incontinentia pigmenti (Bloch-Sulzberger) asso-ciated with proliferative eyeground changes and positive toxo-plasmosis reaction. Acta Psychiatr Scand 1956; 31(suppl 108):197.

6 Fischbein FI, Schub M, Lesko WS. Incontinentia pigmenti,pheochromocytoma and ocular abnormalities. Am J Ophthalmol1972; 73: 961-4.

7 McCrary JA, Smith JL. Conjuntival and retinal incontinentiapigmenti. Arch Ophthalmol 1968; 79: 417-22.

8 Rosenfeld SI, Smith ME. Ocular findings in incontinentiapigmenti. Ophthalmology 1985; 92: 543-6.

9 Rabb EL. Ocular lesions in incontinentia pigmenti. J PediatrOphthalmol Strabismus 1983; 420: 42-8.

10 Mensheha-Manhart 0. Rodriguez MM, Shields JA, ShannonGM, Mirabelli RP. Retinal pigment epithelium in incontinentiapigmenti. Am J Ophthalmol 1975; 79: 571.

Acceptedfor publication 11 August 1986.

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