Flecked Retina Syndromes

Clinical Characteristics

Ocular Features:

There exist a considerable number of disorders often classified under the heading of 'flecked retina' syndrome. Prior to the modern genomic period, distinctions among them were based on the clinical picture, functional abnormalities, and electrophysiological studies. The nosology is becoming clearer as more individuals are genotyped and we can expect further discrimination of these disorders in the near future.

White or yellow discrete dots are found throughout the fundus. These are most dense in the midperiphery RPE and the macula is generally not involved. This is most common in patients with fundus albipunctatus who have a nonprogressive disease. Stationary night blindness is the predominant symptom. However, patients with mutations in RDH5 [1] may have more serious cone involvement and progressive macular disease. Visual acuity varies from near normal to severe loss. Photopic ERGs may be normal but only low scotopic responses can be recorded in such patients. Cone dysfunction is more severe in older patients.

Systemic Features:

No systemic disease is associated with these syndromes.

Genetics

These disorders are sometimes grouped into the category of 'flecked retina disease'.

Autosomal dominant inheritance is typical for fundus albipunctatus [2] (136880 [3]) resulting from mutations in the RDS (PRPH2 [4]) gene (6p21.1-cen).

Autosomal recessive fundus albipunctatus [2] (136880 [3]) is caused by mutations in RDH5 [1] (12q13-q14) and sometimes in RLBP1 [5] (15q26.1).

Retinitis punctata albescens [6] (136880 [3]) and fundus albipunctatus [7] (136880 [3]) may both be caused by mutations in RLBP1 [5] (15q26.1). In a consanguineous family in which younger individuals (aged 3-20 years) had signs of fundus albipunctatis [7], older individuals in the fourth and fifth decades of life had features of retinitis punctata albescens [6] (136880 [3]). Homozygous mutations in RLBP1 [5]were found in all individuals. Homozygous mutations in the same gene are also responsible for Bothnia type retinal dystrophy [8](607475 [9]) and for the Newfoundland type of retinal dystrophy [10] (607476 [11]).

Familial Benign Fleck Retina [12] (228980 [13]) is characterized by a normal ERG and normal vision. The macula is spared from the white/yellow flecks located behind retinal vessels. Autofluorescence is present and the fluorescein angiogram shows irregular hypofluorescence. Nothing is known about the mutation but the clinical condition is inherited in an autosomal recessive pattern.

Some group Stargardt disease [14] (248200 [15]), fleck retina of Kandori [16] (228990 [17]), juvenile retinoschisis [18] (312700 [19]), and familial benign fleck retina [12] (228980 [13]) as well into the category of 'flecked retina disease'.

Other disorders in which retinal flecks may be seen are: spastic paraplegia [20]15 (270700 [21]), hyperoxaluria [22] (259900 [23]), Alport syndrome [24] (301050 [25]), Bietti-crystalline-corneoretinal-dystrophy [26] (210370 [27] ), Sjogren-Larsson syndrome [28](270200 [29]), pantothenate kinase-associated neurodegeneration [30] (234200 [31]), Leber congenital amaurosis [32] (204000 [33]), and Bardet-Biedl syndrome [34] (209900 [35]),

Treatment

Treatment Options:

Low vision aids may be useful when macular disease is present. A recent report describes improvement in peripheral fields and rod function following administration of high-dose oral 9-cis-beta-carotene.

References

Article Title:

Phenotype variations of retinal dystrophies caused by mutations in the RLBP1 gene [36]

Hipp S, Zobor G, Glockle N, Mohr J, Kohl S, Zrenner E, Weisschuh N, Zobor D. Phenotype variations of retinal dystrophies caused by mutations in the RLBP1 gene. Acta Ophthalmol. 2014 Nov 27. [Epub ahead of print].

PubMed ID:

25429852

Novel mutations in RDH5 cause fundus albipunctatus in two consanguineous Pakistani families [37]

Ajmal M, Khan MI, Neveling K, Khan YM, Ali SH, Ahmed W, Iqbal MS, Azam M, den Hollander AI, Collin RW, Qamar R, Cremers FP. Novel mutations in RDH5 cause fundus albipunctatus in two consanguineous Pakistani families. Mol Vis. 2012;18:1558-71.

PubMed ID:

22736946

Treatment of a retinal dystrophy, fundus albipunctatus, with oral 9-cis-{beta}-carotene [38]

Rotenstreich Y, Harats D, Shaish A, Pras E, Belkin M. Treatment of a retinal dystrophy, fundus albipunctatus, with oral 9-cis-{beta}-carotene. Br J Ophthalmol. 2010 May;94(5):616-21.

PubMed ID:

19955196

Flecked-retina syndromes [39]

Walia S, Fishman GA, Kapur R. Flecked-retina syndromes. Ophthalmic Genet. 2009 Jun;30(2):69-75..

PubMed ID:

19373677

Cone and rod dysfunction in fundus albipunctatus with RDH5 mutation: an electrophysiological study [40]

Niwa Y, Kondo M, Ueno S, Nakamura M, Terasaki H, Miyake Y. Cone and rod dysfunction in fundus albipunctatus with RDH5 mutation: an electrophysiological study. Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1480-5.

PubMed ID:

15790919

Novel mutations in the cellular retinaldehyde-binding protein gene (RLBP1) associated with retinitis punctata albescens: evidence of interfamilial genetic heterogeneity and fundus changes in heterozygotes [41]

Fishman GA, Roberts MF, Derlacki DJ, Grimsby JL, Yamamoto H, Sharon D, Nishiguchi KM, Dryja TP. Novel mutations in the cellular retinaldehyde-binding protein gene (RLBP1) associated with retinitis punctata albescens: evidence of interfamilial genetic heterogeneity and fundus changes in heterozygotes. Arch Ophthalmol. 2004 Jan;122(1):70-5.

PubMed ID:

14718298

Macular dystrophy in a 9-year-old boy with fundus albipunctatus [42]

Nakamura M, Miyake Y. Macular dystrophy in a 9-year-old boy with fundus albipunctatus. Am J Ophthalmol. 2002 Feb;133(2):278-80.

PubMed ID:

11812441

Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1 [43]

Katsanis N, Shroyer NF, Lewis RA, Cavender JC, Al-Rajhi AA, Jabak M, Lupski JR. Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1. Clin Genet. 2001 Jun;59(6):424-9. PubMed PMID: 11453974.

PubMed ID:

11453974

Benign fleck retina [44]

Isaacs TW, McAllister IL, Wade MS. Benign fleck retina. Br J Ophthalmol. 1996 Mar;80(3):267-8. PubMed PMID: 8703867

PubMed ID:

8703867