Eye (2004) 18, 421–428 & 2004 Nature Publishing Group All rights reserved 0950-222X/04 $25.00 www.nature.com/eye 1;2 2 1 Macular coloboma F Parmeggiani , E Milan , C Costagliola , CASE REPORT M Giuliano2, A Moro2, P Steindler2 and in siblings affected A Sebastiani1 by different phenotypes of retinitis pigmentosa Abstract Eye (2004) 18, 421–428. doi:10.1038/ Purpose To report the clinical association sj.eye.6700689 between macular coloboma (early-onset mac- ular dystrophies/atrophic changes) and differ- Keywords: macular coloboma; nystagmus; ent phenotypes of retinitis pigmentosa (RP). retinitis pigmentosa; phenotypic heterogeneity Methods Three young-adult siblings, two males and one female, were retrospectively Introduction studied. These patients underwent two Macular coloboma is characterised by a sharply complete ophthalmologic examinations defined, rather large defect in the central area of (27-month follow-up), including orthoptic the fundus that is oval or round, and coarsely evaluation, colour vision test, visual field, pigmented. The condition is thought to result corneal topography, electronystagmography, from intrauterine inflammation or to be an fluorescein angiography, and electroretino- abnormality of development. A developmental graphy. Eye check, automated visual field test, alteration seems to be the cause thereof (i.e. of and complete electroretinographic study were the condition) among those patients with a also conducted on other asymptomatic hereditary or family origin,1–3 and among those members of the same family. with other ocular or systemic abnormalities.4–11 Results All symptomatic siblings were Several reports have described patients with affected by manifest congenital nystagmus, macular coloboma associated with peripheral poor visual acuity, and progressive visual field retinal changes such as retinitis pigmentosa impairment in both eyes, bilaterally (RP),4 retinal aplasia,5 Leber’s congenital presenting macular coloboma associated with amaurosis,6,7 retinal dystrophy,8,9 progressive three different RP patterns: classic RP; mild atrophy of the peripheral retina,10 or pigmented dystrophy of the retinal pigment epithelium, paravenous retinochoroidal atrophy.11 associated with subnormal electro- The purpose of this paper is to present the 1Department of retinographic findings (subclinical form of clinical characteristics in three adult siblings Ophthalmology RP); and sector RP. The ophthalmologic who exhibited a bilateral macular coloboma University of Ferrara reports regarding their deceased father (early-onset macular dystrophies/atrophic Ferrara, Italy documented that he had suffered from the changes), associated with different RP pheno- 2 same alterations of ocular movements and types. We are unaware of previous reports of Division of Ophthalmology visual performances diagnosing, in both eyes, Camposampiero Hospital nonsporadic concomitance between macular Camposampiero (PD), Italy extensive atrophic changes of the macular area coloboma and heterogeneous intrafamilial RP completely surrounded by pigmented bone patterns and could find no reference to it in a Correspondence: spicules (RP-type tapeto-retinal dystrophy). computerised search utilising Medline. F Parmeggiani The other investigated relatives did not show Via Palestro any specific and/or significant ocular disorder. Case reports 41 44100 Ferrara, Italy Conclusions In these three adult members of Tel: þ 39 532 202331 the same family, the concomitance between We retrospectively analysed six members of a Fax: þ 39 532 210424 E-mail: f.parmeggiani@ macular coloboma and different intrafamilial nonconsanguineous family coming from the tiscali.it RP phenotypes is described. This association South of Italy (the mother, three daughters, and represents an autosomal dominant clinical two sons), who were admitted at our Clinic Received: 10 February 2003 entity, hitherto observed only in non familial from September 2000 to January 2003. Only the Accepted in revised form: sporadic cases. three symptomatic patients (two sons and a 25 July 2003 Different RP phenotypes and bilateral macular coloboma F Parmeggiani et al 422 daughter) underwent two complete ophthalmologic I examinations (27-month follow-up), including orthoptic evaluation, colour vision test, visual field, corneal 4 topography, electronystagmography, fluorescein II angiography (FA), and electroretinography (ERG). Eye check, automated visual field test, and complete ERGs III 6 1 5 2 3 study were also conducted on the other asymptomatic members of this family (the mother and two daughters). Lens assessment was performed according to the Lens 12 Opacities Classification System III (LOCS III). Figure 1 Pedigree of this macular coloboma/RP family; the Computed corneal topographic studies were conducted ocular alterations are characterised by an autosomal dominant by Optikon 2000 Keratron Corneal Analysis System model inheritance. (Optikon 2000 S.p.A., Roma, Italy). All ocular electrophysiological findings were achieved by Modular early-onset nystagmus and poor visual acuity; whereas System BM-6000W and an Olivetti-I.B.M. personal the orthoptic and ophthalmologic reports of their computer (Biomedica Mangoni, Pisa, Italy). father (deceased) documented that he was bilaterally Electronystamographic waveform analyses were carried affected by: (i) congenital nystagmus (horizontal and out using skin electrodes positioned at all four canthi, a pendular); (ii) both central and peripheral total ground electrode placed on the forehead, and the blindness; (iii) absence of pupillary light reaction optokinetic stimulator type BM1620 with a semicircular in pseudophakic eye treated with Nd:YAG laser bar (type BM1620-C). Full-field, scotopic, and photopic capsulotomy; (iv) marked and diffuse vitreous ERGs were recorded by employing Henkes corneal degeneration; and (v) extensive atrophic changes contact lens ERG electrodes and a ground electrode on and pigment clumps at the level of the macular area, the forehead. In each eye, the ERG tracings were associated with waxy pallor of the optic disc, obtained after maximal pupil dilatation with topical 10% very restricted retinal vessels and several mid-peripheral phenylephrine hydrochloride, according to the ISCEV pigmented bone spicules (RP-type tapeto-retinal parameters.13 The results of the electrophysiological dystrophy). Several ophthalmologic findings, including responses were compared with the normal values best-corrected visual acuity, colour vision, intraocular obtained by examining 100 normal subjects, who had pressure, anterior segment slit-lamp examination, cyclo- been referred to our clinic for different reasons, but with plegic ametropia, corneal topography, and electrore- no detectable eye disorder and with normal visual acuity. tinography, of the three affected members are summa- The three symptomatic siblings reported a very early- rised in Table 1 (Cases 1–3). onset nystagmus (in all cases firstly diagnosed during the third or fourth month of life), poor visual acuity, Case 1 progressive and different visual field impairments. In each of these patients, the first available In September 2000, a 38-year-old man came under our ophthalmoscopic reports, recorded when they were observation for a life-long history of nystagmus, between 12 and 15 months old, indicated the presence of photodysphoria, and markedly reduced visual acuity, an oval dystrophic macular lesion in both the eyes. followed by nyctalopia and progressive visual field At the time of our examination, orthoptic evaluation constriction. Goldmann kinetic perimetry, performed and electronystagmography performed in each subject by a standardised V-4-e target, bilaterally documented bilaterally showed a horizontal nystagmus, which was the presence of a restricted remaining vision area more evident in the elder son; the eyes oscillated with the in the inferior-nasal sector that was larger in the same velocity in both directions (pendular nystagmus), right eye (Figure 2a, b). Ophthalmoscopic assuming a jerky character in the extreme positions of examination bilaterally revealed posterior vitreous gaze. In all patients, these involuntary and rhythmic detachment and diffuse vitreous degeneration, several conjugate oscillation of the eyes appeared as manifest wide patches of chorioretinal geographic atrophy, congenital forms of nystagmus, typically characterised associated with waxy pallor of the optic disc, atten- by: (i) biphasic, mostly pendular movements; (ii) uated retinal vessels, rare mid-peripheral bone spicules increasing velocity in the slow phase; and (iii) no and several pigment clumps, located only in the macular change on unilateral occlusion.14 The medical and drug atrophic area. FA revealed widespread retinal pigment histories of all the three siblings were unremarkable. epithelium (RPE) depigmentation, and detailed the Their familial history (Figure 1) revealed that the atrophic features of both posterior poles (Figure 2c, d). paternal grandfather (deceased) had suffered from All the ERG tracings were nonrecordable (Table 1, Case 1). Eye Table 1 Summary of the ocular findings observed in six members of the same family: the mother (Case 4), and five siblings (Cases 1–3, 5, and 6) Case Sex Age Initial Best Colour intraocular Anterior Cycloplegic Corneal September 2000 January 2003 Final no. (years) sym- corrected vision pressure segment ametropia topographic diagnosis ptoms visual (UO) (mmHg) examination (TABO) curvature (TABO) Full-field Scotopic ERG Photopic Full-field Scotopic acuity (UO, ERG (mV)