enhanced S-cone syndrome

Goldmann-Favre Syndrome/ESCS

Clinical Characteristics

Ocular Features

Enhanced S-cone syndrome, sometimes called Goldman-Favre syndrome, is a retinal disorder characterized by increased sensitivity to blue light, night blindness from an early age, and decreased vision.  Additional features include an optically empty liquefied vitreous, progressive foveal or peripheral retinoschisis, macular cysts, chorioretinal atrophy and pigmentary retinopathy as well as posterior subcapsular cataract formation.  Hyperopia is a feature, at least in childhood.   Enhanced S-cone syndrome is the only retinal disorder that has a gain of a subtype of photoreceptors, in this case the S-cones (short wave length) that detect blue light. Rod photoreceptors and red and green cone receptors are degenerated to a variable degree. Electroretinography shows an extinct rod photoreceptor response and hypersensitivity to shorter wavelengths.

There is considerable variation in the clinical features of NR2E3 mutations which has led to some confusion in the nosology.  Some cases are called juvenile retinoschisis, others are called retinitis pigmentosa, or clumped pigment retinopathy.  Central acuity ranges from near normal (20/40) in young people to 20/200 or worse especially in older adults.  Visual field constriction likewise varies from patient to patient.  Retinal pigmentary changes and the amount of cystic changes in the macula are somewhat age dependent.

Systemic Features

No general systemic manifestations are associated with enhanced S-cone syndrome and Goldman-Favre syndrome.

Genetics

This is an autosomal recessive retinal disorder caused by mutations in NR2E3, also called the photoreceptor-specific nuclear receptor, PNR, located on chromosome 15q23.  It is a part of a transcription factor complex necessary for the development of photoreceptors.  Mutations in NR2E3 cause degeneration of rod photoreceptors and an increased number of S-cone photoreceptors resulting in an increased ratio of blue to red-green cone photoreceptors. Mutations in the NR2E3 gene can also cause a clinical picture resembling simple autosomal recessive retinitis pigmentosa.

Two brothers with an enhanced S-cone phenotype and normal rod function have been reported.  Scotopic b-wave ERG amplitudes were normal but OCT showed flattening of the mcaular area and thinning of the photoreceptor layer.  This may be the result of a different mutation in this family but no molecular defect was found.

Treatment Options

There is presently no effective treatment for the disorder, but visual function can be improved with low vision aids. Cataract surgery may be beneficial.

Improvement in vision has been reported with the use of topical carbonic anhydrase inhibitors.

References

Hull S, Arno G, Sergouniotis PI, Tiffin P, Borman AD, Chandra A, Robson AG, Holder GE, Webster AR, Moore AT. Clinical and Molecular Characterization of Enhanced S-Cone Syndrome in Children. JAMA Ophthalmol. 2014 Jul 31. [Epub ahead of print].

PubMed ID: 
25079116

Yzer S, Barbazetto I, Allikmets R, van Schooneveld MJ, Bergen A, Tsang SH, Jacobson SG, Yannuzzi LA. Expanded Clinical Spectrum of Enhanced S-Cone Syndrome. JAMA Ophthalmol. 2013 Aug 29.  [Epub ahead of print] PubMed PMID: 23989059.

PubMed ID: 
23989059

Kinori M, Pras E, Kolker A, Ferman-Attar G, Moroz I, Moisseiev J, Bandah-Rozenfeld D, Mizrahi-Meissonnier L, Sharon D, Rotenstreich Y. Enhanced S-cone function with preserved rod function: a new clinical phenotype. Mol Vis. 2011;17:2241-7. Epub 2011 Aug 18.

PubMed ID: 
21897746

Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, Beck G, Hockey R, Hanna DB, Gorman S, Duhl D, Carmi R, Bennett J, Weleber RG, Fishman GA, Wright AF, Stone EM, Sheffield VC. Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet. 2000 Feb;24(2):127-31.

PubMed ID: 
10655056

Schorderet DF, Escher P. NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP). Hum Mutat. 2009 Nov;30(11):1475-85.

PubMed ID: 
19718767

Pachydaki SI, Klaver CC, Barbazetto IA, Roy MS, Gouras P, Allikmets R, Yannuzzi LA. Phenotypic features of patients with NR2E3 mutations. Hum Mutat. 2009 Mar;30(3):342-51.

PubMed ID: 
19139342

Hajali M, Fishman GA. Dorzolamide use in the management of macular cysts in a patient with enhanced s-cone syndrome. Retin Cases Brief Rep. 2009 Spring;3(2):121-4.

PubMed ID: 
25391052

Audo I, Michaelides M, Robson AG, Hawlina M, Vaclavik V, Sandbach JM, Neveu MM, Hogg CR, Hunt DM, Moore AT, Bird AC, Webster AR, Holder GE. Phenotypic variation in enhanced S-cone syndrome. Invest Ophthalmol Vis Sci. 2008 May;49(5):2082-93.

PubMed ID: 
18436841