FOUR-GENERATION FAMILIAL BENIGN FLECK RETINA Syril K. Dorairaj, MD,*† Krishna R. Murthy, MBBS, DNB,† Robert Ritch, MD*‡
The authors report a case of benign familial flecked retina with possible autosomal dominant inheritance, based on a pedigree analysis of four-generations. A total of eight affected individuals were identified from one family, none who had ocular abnormalities aside from the retinal flecks. The authors also describe a progressive age-dependent darkening and confluence of flecks with time with typical phenotypic expression between 1 and 2 years.
From the *Department of Ophthalmology, The New York Eye and Ear Infirmary, New York, New York, USA; the †Department of Ophthalmology, Minto Ophthalmic Hospital, Bangalore, India; and the ‡Department of Ophthalmology, New York Medical College, Valhalla, New York, USA.
W
e describe a four-generation family with multiple subjects affected with benign fleck retina. None of the eight affected individuals had any ocular abnormalities other than the retinal findings, and results of electrophysiological testing were normal. Pedigree analysis suggests a possible autosomal dominant inheritance with phenotype expression between 1 year and 2 years. Case Report
A 14-year-old boy presented for a routine eye examination. He had a history of occasional headaches with no specific ocular complaints. At examination, best-corrected visual acuity was 20/20 in both eyes. The anterior segments were unremarkable. Fundus examination revealed multiple cream discreet flecks scattered uniformly across the retina in both eyes, sparing the fovea (Fig. 1). Slit-lamp biomicroscopy demonstrated that the lesions were flat and not raised and the retinal vessels were coursing normally over them. The flecks were distributed in a concentric pattern around the posterior fundus with a varied configuration, the centrally located flecks being round to oblong and the more peripheral flecks extending up to the equator being larger in dimension with sinusoidal or amoeboid outlines. The disks and maculae appeared normal, and the retinal vessels were of normal diameter and distribution. Visual fields were normal in both eyes. Fundus fluorescein angiography showed multiple discrete hyperfluorescent lesions in the early frames. The intensity of hyperfluorescence decreased in the late frames of the angiogram, suggesting transmission defects. Color vision by Ishihara pseudochromatic plates and results of Farnsworth dichotomous (D-15) testing were normal for both eyes. The full-field electroretinogram recorded under both photopic and scotopic conditions was normal for both eyes.
Fig. 1. Proband (III-4). Fundus picture showing discreet flecks with varied configuration sparing the fovea and optic disk.
The proband’s mother (Fig. 2) and two siblings (III-2 and III-3) were affected, but the configuration of the flecks differed (Fig. 3). Some of the siblings of the mother (II-1 and II-6) were also affected (pedigree chart; Fig. 4). It is interesting that the child (IV-1) born out of a second-degree consanguineous marriage between two affected parents (III-1 and III-2) at 6 months of age had a normal fundus but when reexamined at 18 months of age had the typical fundus picture described, although the flecks were much smaller and fewer in number. The proband’s mother had a slightly different pattern, with much smaller central flecks and the more peripheral lesions assuming the typical large flecks described. However, none of the family members examined had a history of any ocular complaints and had no ocular or systemic abnormalities by clinical and electrophysiological testing.
Discussion The term “flecked retina” was introduced by Krill and Klien1 to describe fundus conditions characterized by multiple yellowish white lesions of various sizes and configuration, without vascular or optic nerve abnormalities. Originally, this group consisted of four
Reprint requests: Syril K. Dorairaj, MD, Glaucoma Services, The New York Eye and Ear Infirmary, 310 East 14th Street, New York, NY 10003; e-mail: [email protected]
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Fig. 2. Proband’s mother (II-3). Fundus picture showing a different pattern with the central flecks much smaller and fewer and the peripheral flecks larger and confluent.
diseases: fundus albipunctatus, fundus flavimaculatus, familial drusen, and fleck retina of Kandori.2 In 1980, Aish and Dajani3 described a new entity, “benign familial fleck retina,” in an Arab Palestinian family from Jordan and suggested that it constitutes a fifth type of the disease. Seven of the 10 siblings they examined were affected by this condition, with affected younger members having sparser and immature flecks. They suggested a possible autosomal recessive mode of inheritance, because both the parents were unaffected. Isaacs et al4 described a similar case in a 20-year-old girl of mixed Australian aborigine and white descent. However, no other family member was affected. These investigators were of the opinion that it was probably a new mutation or an autosomal recessive inheritance.
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Fig. 4. Pedigree chart of the four-generation family affected with familial benign flecked retina. Arrow indicates the index case. Black stars denote the fundus pictures included in this report. A circle represents a female and a square represents a male. Shaded symbols imply affected individuals and a slash mark implies deceased.
More recently, Tsuchiya et al5 described an isolated case of sectorial benign flecked retina in a Japanese family. To our knowledge, this is the second report in the literature where multiple family members have been affected. The findings described in these subjects fit into a diagnosis of benign familial flecked retina. The patients typically had no ocular complaints. They had no ocular abnormalities other than the retinal findings, and the results of electrophysiological testing were within normal limits. The pedigree analysis in our study suggests an autosomal dominant pattern of inheritance and differs from the previous two case reports where the inheritance appeared to be autosomal recessive. We also observed that there were no noticeable flecks in the affected individual (IV-1) at initial clinical examination; however, with age, sparser and immature flecks started to appear. The flecks also became more prominent, darker, and confluent at subsequent examinations. Similar findings were also reported by Aish and Dajani.3 We infer that precise diagnosis of benign familial fleck retina not only is based on the close observation of the fundus but also could require electrophysiological examination of the patient to rule out other vision-threatening causes of flecked retina like fundus albipunctatus and fundus flavimaculatus. Key words: familial, benign, fleck, retina. References 1. 2. 3. 4.
Fig. 3. Proband’s sibling (III-3). Fundus picture similar to that of the proband with discreet flecks with smooth sinuous and geographical outlines.
5.
Krill AE, Klien BA. Flecked retina syndrome. Arch Ophtalmol (Paris) 1965;74:496–508. Kandori F, Tamai A, Kurimoto S, Fukunaga K. Fleck retina. Am J Ophthalmol 1972;73:673–685. Aish SF, Dajani B. Benign familial fleck retina. Br J Ophthalmol 1980;64:652–659. Isaacs TW, McAllister IL, Wade MS. Benign fleck retina. Br J Ophthalmol 1996;80:267–268. Tsuchiya T, Kato M, Tomita N, et al. A case of sectorial benign flecked retina. Jpn J Ophthalmol 2004;48:72–74.
The authors report a case of benign familial flecked retina with possible autosomal dominant inheritance, based on a pedigree analysis of four-generations. A total of eight affected individuals were identified from one family, none who had ocular abnormalities aside from the retinal flecks. The authors also describe a progressive age-dependent darkening and confluence of flecks with time with typical phenotypic expression between 1 and 2 years.
From the *Department of Ophthalmology, The New York Eye and Ear Infirmary, New York, New York, USA; the †Department of Ophthalmology, Minto Ophthalmic Hospital, Bangalore, India; and the ‡Department of Ophthalmology, New York Medical College, Valhalla, New York, USA.
W
e describe a four-generation family with multiple subjects affected with benign fleck retina. None of the eight affected individuals had any ocular abnormalities other than the retinal findings, and results of electrophysiological testing were normal. Pedigree analysis suggests a possible autosomal dominant inheritance with phenotype expression between 1 year and 2 years. Case Report
A 14-year-old boy presented for a routine eye examination. He had a history of occasional headaches with no specific ocular complaints. At examination, best-corrected visual acuity was 20/20 in both eyes. The anterior segments were unremarkable. Fundus examination revealed multiple cream discreet flecks scattered uniformly across the retina in both eyes, sparing the fovea (Fig. 1). Slit-lamp biomicroscopy demonstrated that the lesions were flat and not raised and the retinal vessels were coursing normally over them. The flecks were distributed in a concentric pattern around the posterior fundus with a varied configuration, the centrally located flecks being round to oblong and the more peripheral flecks extending up to the equator being larger in dimension with sinusoidal or amoeboid outlines. The disks and maculae appeared normal, and the retinal vessels were of normal diameter and distribution. Visual fields were normal in both eyes. Fundus fluorescein angiography showed multiple discrete hyperfluorescent lesions in the early frames. The intensity of hyperfluorescence decreased in the late frames of the angiogram, suggesting transmission defects. Color vision by Ishihara pseudochromatic plates and results of Farnsworth dichotomous (D-15) testing were normal for both eyes. The full-field electroretinogram recorded under both photopic and scotopic conditions was normal for both eyes.
Fig. 1. Proband (III-4). Fundus picture showing discreet flecks with varied configuration sparing the fovea and optic disk.
The proband’s mother (Fig. 2) and two siblings (III-2 and III-3) were affected, but the configuration of the flecks differed (Fig. 3). Some of the siblings of the mother (II-1 and II-6) were also affected (pedigree chart; Fig. 4). It is interesting that the child (IV-1) born out of a second-degree consanguineous marriage between two affected parents (III-1 and III-2) at 6 months of age had a normal fundus but when reexamined at 18 months of age had the typical fundus picture described, although the flecks were much smaller and fewer in number. The proband’s mother had a slightly different pattern, with much smaller central flecks and the more peripheral lesions assuming the typical large flecks described. However, none of the family members examined had a history of any ocular complaints and had no ocular or systemic abnormalities by clinical and electrophysiological testing.
Discussion The term “flecked retina” was introduced by Krill and Klien1 to describe fundus conditions characterized by multiple yellowish white lesions of various sizes and configuration, without vascular or optic nerve abnormalities. Originally, this group consisted of four
Reprint requests: Syril K. Dorairaj, MD, Glaucoma Services, The New York Eye and Ear Infirmary, 310 East 14th Street, New York, NY 10003; e-mail: [email protected]
25
26
RETINAL CASES & BRIEF REPORTSℜ
Fig. 2. Proband’s mother (II-3). Fundus picture showing a different pattern with the central flecks much smaller and fewer and the peripheral flecks larger and confluent.
diseases: fundus albipunctatus, fundus flavimaculatus, familial drusen, and fleck retina of Kandori.2 In 1980, Aish and Dajani3 described a new entity, “benign familial fleck retina,” in an Arab Palestinian family from Jordan and suggested that it constitutes a fifth type of the disease. Seven of the 10 siblings they examined were affected by this condition, with affected younger members having sparser and immature flecks. They suggested a possible autosomal recessive mode of inheritance, because both the parents were unaffected. Isaacs et al4 described a similar case in a 20-year-old girl of mixed Australian aborigine and white descent. However, no other family member was affected. These investigators were of the opinion that it was probably a new mutation or an autosomal recessive inheritance.
●
2007
●
VOLUME 1
●
NUMBER 1
Fig. 4. Pedigree chart of the four-generation family affected with familial benign flecked retina. Arrow indicates the index case. Black stars denote the fundus pictures included in this report. A circle represents a female and a square represents a male. Shaded symbols imply affected individuals and a slash mark implies deceased.
More recently, Tsuchiya et al5 described an isolated case of sectorial benign flecked retina in a Japanese family. To our knowledge, this is the second report in the literature where multiple family members have been affected. The findings described in these subjects fit into a diagnosis of benign familial flecked retina. The patients typically had no ocular complaints. They had no ocular abnormalities other than the retinal findings, and the results of electrophysiological testing were within normal limits. The pedigree analysis in our study suggests an autosomal dominant pattern of inheritance and differs from the previous two case reports where the inheritance appeared to be autosomal recessive. We also observed that there were no noticeable flecks in the affected individual (IV-1) at initial clinical examination; however, with age, sparser and immature flecks started to appear. The flecks also became more prominent, darker, and confluent at subsequent examinations. Similar findings were also reported by Aish and Dajani.3 We infer that precise diagnosis of benign familial fleck retina not only is based on the close observation of the fundus but also could require electrophysiological examination of the patient to rule out other vision-threatening causes of flecked retina like fundus albipunctatus and fundus flavimaculatus. Key words: familial, benign, fleck, retina. References 1. 2. 3. 4.
Fig. 3. Proband’s sibling (III-3). Fundus picture similar to that of the proband with discreet flecks with smooth sinuous and geographical outlines.
5.
Krill AE, Klien BA. Flecked retina syndrome. Arch Ophtalmol (Paris) 1965;74:496–508. Kandori F, Tamai A, Kurimoto S, Fukunaga K. Fleck retina. Am J Ophthalmol 1972;73:673–685. Aish SF, Dajani B. Benign familial fleck retina. Br J Ophthalmol 1980;64:652–659. Isaacs TW, McAllister IL, Wade MS. Benign fleck retina. Br J Ophthalmol 1996;80:267–268. Tsuchiya T, Kato M, Tomita N, et al. A case of sectorial benign flecked retina. Jpn J Ophthalmol 2004;48:72–74.
