nyctalopia

Retinitis Pigmentosa 77

Clinical Characteristics
Ocular Features: 

The onset of nyctalopia apparently varies from early childhood to 20 years of age and is usually the presenting symptom.  The loss of acuity is progressive (20/30 to 20/400) with older patients generally having more severe loss but there is little direct correlation with age.  Peripheral fields are progressively constricted, ranging from 10 to 30 degrees.  Some patients develop posterior subcapsular cataracts.  Retinal pigmentation is often mottled but 'bone spicules' are seen in about half of individuals.  Retinal vessels are narrowed.  The ERG shows generalized rod-cone dystrophy.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

Homozygous or compound heterozygous mutations in the REEP6 gene (19p13.3) are responsible for this disorder.  Five unrelated families have been reported.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported although cataract removal may be visually beneficial.  

References
Article Title: 

Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa

Arno G, Agrawal SA, Eblimit A, Bellingham J, Xu M, Wang F, Chakarova C, Parfitt DA, Lane A, Burgoyne T, Hull S, Carss KJ, Fiorentino A, Hayes MJ, Munro PM, Nicols R, Pontikos N, Holder GE; UKIRDC., Asomugha C, Raymond FL, Moore AT, Plagnol V, Michaelides M, Hardcastle AJ, Li Y, Cukras C, Webster AR, Cheetham ME, Chen R. Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa. Am J Hum Genet. 2016 Dec 1;99(6):1305-1315.

PubMed ID: 
27889258

Night Blindness, Congenital Stationary, CSNB1H

Clinical Characteristics
Ocular Features: 

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  However, the photopic ERG can be abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

Night blindness in this condition can be detected in early childhood and may be congenital.   Photophobia, reduced cone sensitivity. and mild dyschromatopsia may develop in midlife.  Peripheral field constriction can be demonstrated.  Visual acuity is near normal and there is no nystagmus or high myopia as reported for some other forms of CSNB.   

Systemic Features: 

There are no systemic abnormalities.

Genetics

This is an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in the GNB3 gene (12p13.31).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment has been reported but the use of tinted lenses can enhance contrast and improve acuity.

References
Article Title: 

Night Blindness, Congenital Stationary, CSNB1E

Clinical Characteristics
Ocular Features: 

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  The photopic ERG is usually abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

The onset of night blindness in type 1E occurs in early childhood and may be congenital.  Some degree of nystagmus is usually present.  It is usually only slowly progressive.

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

This type of congenital stationary night blindness is inherited in an autosomal recessive pattern resulting from homozygous or compound heterozygous mutations in GPR179.  The gene encodes an orphan G protein receptor.

Other autosomal recessive CSNB disorders are: CSNB2B (610427), CSNB1B (257270), and CSNB1C (613216).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment beyond correction of the refractive error is available but tinted lenses are sometimes used to enhance vision.

References
Article Title: 

Whole-Exome Sequencing Identifies Mutations in GPR179 Leading to Autosomal-Recessive Complete Congenital Stationary Night Blindness

Audo I, Bujakowska K, Orhan E, Poloschek CM, Defoort-Dhellemmes S, Drumare I, Kohl S, Luu TD, Lecompte O, Zrenner E, Lancelot ME, Antonio A, Germain A, Michiels C, Audier C, Letexier M, Saraiva JP, Leroy BP, Munier FL, Mohand-Sa?Od S, Lorenz B, Friedburg C, Preising M, Kellner U, Renner AB, Moskova-Doumanova V, Berger W, Wissinger B, Hamel CP, Schorderet DF, De Baere E, Sharon D, Banin E, Jacobson SG, Bonneau D, Zanlonghi X, Le Meur G, Casteels I, Koenekoop R, Long VW, Meire F, Prescott K, de Ravel T, Simmons I, Nguyen H, Dollfus H, Poch O, L?(c)veillard T, Nguyen-Ba-Charvet K, Sahel JA, Bhattacharya SS, Zeitz C. Whole-Exome Sequencing Identifies Mutations in GPR179 Leading to Autosomal-Recessive Complete Congenital Stationary Night Blindness. Am J Hum Genet. 2012 Feb 10;90(2):321-30.

PubMed ID: 
22325361

GPR179 Is Required for Depolarizing Bipolar Cell Function and Is Mutated in Autosomal-Recessive Complete Congenital Stationary Night Blindness

Peachey NS, Ray TA, Florijn R, Rowe LB, Sjoerdsma T, Contreras-Alcantara S, Baba K, Tosini G, Pozdeyev N, Iuvone PM, Bojang P Jr, Pearring JN, Simonsz HJ, van Genderen M, Birch DG, Traboulsi EI, Dorfman A, Lopez I, Ren H, Goldberg AF, Nishina PM, Lachapelle P, McCall MA, Koenekoop RK, Bergen AA, Kamermans M, Gregg RG. GPR179 Is Required for Depolarizing Bipolar Cell Function and Is Mutated in Autosomal-Recessive Complete Congenital Stationary Night Blindness. Am J Hum Genet. 2012 Feb 10;90(2):331-9.

PubMed ID: 
22325362

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 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 (136880) resulting from mutations in the RDS (PRPH2) gene (6p21.1-cen).

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

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

Familial Benign Fleck Retina (228980) 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 (248200), fleck retina of Kandori (228990),  juvenile retinoschisis (312700), and familial benign fleck retina (228980) as well into the category of 'flecked retina disease'.

Other disorders in which retinal flecks may be seen are: spastic paraplegia 15 (270700), hyperoxaluria (259900), Alport syndrome (301050), Bietti-crystalline-corneoretinal-dystrophy (210370 ), Sjogren-Larsson syndrome (270200), pantothenate kinase-associated neurodegeneration (234200), Leber congenital amaurosis (204000), and Bardet-Biedl syndrome (209900),

Pedigree: 
Autosomal dominant
Autosomal recessive
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: 

Flecked-retina syndromes

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

PubMed ID: 
19373677

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

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

Benign fleck retina

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

PubMed ID: 
8703867

Oguchi Disease, Type 2

Clinical Characteristics
Ocular Features: 

The distinctive feature of Oguchi disease is the peculiar and distinctive discoloration of the fundus under various light conditions, known as the Mizuo phenomenon.  Typically, the fundus assumes a golden or gray-white coloration under light adapted conditions but this disappears during acute dark adaptation and only reappears after prolonged time spent in darkness.  Rod dark adaptation is markedly delayed while that of cones is normal.  Single flash cone and 30Hz flicker responses are markedly reduced.  Visual acuity, visual fields and color vision are all normal.   A- and b-waves on single flash ERG are decreased or absent under lighted conditions but increase after prolonged dark adaptation.  Night blindness is present from birth without progression.

Systemic Features: 

No systemic abnormalities are associated with Oguchi disease.

Genetics

Oguchi type 2 disease is an autosomal recessive condition caused by mutations in the rhodopsin kinase (GRK1) gene (13q34) whose product works with arrestin in turning off rhodopsin after light activation as part of the dark adaptation mechanism.

Oguchi type 1 disease (258100) is a similar form of congenital stationary nightblindness caused by mutations in the SAG gene.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available.

References
Article Title: 

Oguchi Disease, Type 1

Clinical Characteristics
Ocular Features: 

The distinctive feature of Oguchi disease is the peculiar and distinctive discoloration of the fundus under various light conditions, known as the Mizuo phenomenon.  Typically, the fundus assumes a golden or gray-white coloration under light adapted conditions but this disappears during acute dark adaptation and only reappears after prolonged time spent in darkness.  Rod dark adaptation is markedly delayed while that of cones is normal.  Visual acuity, visual fields and color vision are all normal.   A- and b-waves on single flash ERG are decreased or absent under lighted conditions but increase after prolonged dark adaptation.  Night blindness is present from birth without progression.

Systemic Features: 

No systemic abnormalities are associated with Oguchi disease.

Genetics

Oguchi type 1 disease is an autosomal recessive condition caused by mutations in the arrestin (SAG) gene (2q37.1) whose product is an intrinsic photoreceptor protein that participates in the recovery phase of light transduction.

Oguchi disease type 2 (613411), a similar form of congenital stationary night blindness, is caused by mutations in the GRK1 gene.  Genotyping is required to distinguish between the two types.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available.

References
Article Title: 

Night Blindness, Congenital Stationary, CSNBAD3

Clinical Characteristics
Ocular Features: 

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  However, the photopic ERG can be abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

Congenital stationary night blindness disorders are primarily rod dystrophies presenting early with symptoms of nightblindness and relative sparing of central vision.  Nystagmus and photophobia are usually not features.  Dyschromatopsia and loss of central acuity can develop later as the cones eventually become dysfunctional as well but these symptoms are much less severe than those seen in cone-rod dystrophies.  The amount of pigmentary retinopathy is highly variable.

This disorder (CSNBAD3), one of three autosomal dominant CSNB conditions, is known primarily from  a single large family in Southern France.  All affected individuals descended from Jean Nougaret from which the eponym is derived.  The published pedigree by F. Cunier in 1838 is probably the first illustrating autosomal dominant inheritance of a human disease.  Rod a-waves are completely absent suggesting complete lack of rod function.  Night vision in dim conditions was reduced but not with bright backgrounds.  Daytime vision is normal as is color vision.  Rare patients have peripheral pigmentary changes with visual field restriction.

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

CSNBAD3, or type AD3, is one of three congenital nightblindness disorders with autosomal dominant inheritance.  It results from mutations in the GNAT1 gene (3p21) gene encoding a subunit of rod transducin which couples rhodopsin as part of the phototransduction cascade.

A consanguineous Pakistani family with 4 affected children in a pedigree suggestive of autosomal recessive inheritance has been reported (CSNB1G).  All individuals with congenital nightblindness were homozygous for a missense mutation in GNAT1 while unaffected persons were heterozygous (616389).

Other autosomal dominant CSNB disorders are: CSNBAD2 (163500) and CSNBAD1 (610445).  Three CSNB disorders are transmitted in an autosomal recessive pattern and two as X-linked recessives.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment beyond correction of the refractive error is available but tinted lenses are sometimes used to enhance vision.

References
Article Title: 

Night Blindness, Congenital Stationary, CSNBAD2

Clinical Characteristics
Ocular Features: 

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  However, the photopic ERG can be abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

Congenital stationary night blindness disorders are primarily rod dystrophies presenting early with symptoms of nightblindness and relative sparing of central vision.  Nystagmus and photophobia are usually not features.  Dyschromatopsia and loss of central acuity can develop later as the cones eventually become dysfunctional as well but these symptoms are much less severe than those seen in cone-rod dystrophies.  The amount of pigmentary retinopathy is highly variable.

This disorder (CSNBAD2) is one of three autosomal dominant CSNB conditions.  ERG responses were identical to those found in the Nougaret type of autosomal dominant CSNB.  Rod a-wave responses to single flashes are completely absent suggesting complete lack of rod function.  The residual b-wave suggests some cone response.  Daytime and color vision are normal.

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

CSNBAD2, or type AD2, is one of three congenital nightblindness disorders with autosomal dominant inheritance.  It results from mutations in the PDE6B gene (4p16.3) encoding a subunit of rod cGMP-specific phosphodiesterase.

Other CSNB disorders inherited in an autosomal dominant pattern are CSNBAD1 (610445) and CSNBAD3 (610444).

Three CSNB disorders are transmitted in an autosomal recessive pattern and two as X-linked recessives.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment beyond correction of the refractive error is available but tinted lenses are sometimes used to enhance vision.

References
Article Title: 

Night Blindness, Congenital Stationary, CSNBAD1

Clinical Characteristics
Ocular Features: 

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  The photopic ERG is usually abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

Congenital stationary night blindness disorders are primarily rod dystrophies presenting early with symptoms of nightblindness and relative sparing of central vision.  Nystagmus and photophobia are usually not features.  Dyschromatopsia and loss of central acuity can develop later as the cones eventually become dysfunctional as well but these symptoms are much less severe than those seen in cone-rod dystrophies.  The amount of pigmentary retinopathy is highly variable. 

In this disorder (CSNBAD1), one of three autosomal dominant CSNB conditions, the b-wave responses are absent (no scotopic response) with some a-wave decrease in amplitude under dark adapted conditions.  Night vision in dim conditions may be reduced but not with bright backgrounds.  Daytime vision is normal as is color vision.  Older patients can have peripheral bone-spicule pigmentary changes with visual field restriction and narrowing of retinal arterioles.

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

CSNBAD1, or type AD1, is one of three congenital nightblindness disorders with autosomal dominant inheritance.  It results from mutations in the RHO (3q21-q24) gene coding rhodopsin.

Other autosomal dominant CSNB disorders are: CSNBAD2 (163500) and CSNBAD3 (610444).  Three CSNB disorders are transmitted in an autosomal recessive pattern and 2 as X-linked recessives.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment beyond correction of the refractive error is available but tinted lenses are sometimes used to enhance vision.

References
Article Title: 

Night Blindness, Congenital Stationary, CSNB2B

Clinical Characteristics
Ocular Features: 

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  The photopic ERG is usually abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

In this disorder (CSNB2B) the b-wave responses are deficient (little or no scotopic response) and a-waves seem to be normal.  However, many if not most patients do not complain of night blindness.  Nystagmus, strabismus, and restriction of visual fields may be present.  Visual acuity is mildly to severely reduced.

Foveal thinning has been documented in this condition.

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

CSNB2B, or type 2B, is one of four congenital nightblindness disorders with autosomal recessive inheritance.  It results from mutations in the CAPB4 gene (11q13.1) important in receptor to bipolar cell signaling.

Other autosomal recessive CSNB disorders are: CSNB1C (613216), CSNB (unclassified; OMIM number pending), and CSNB1B (257270).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment beyond correction of the refractive error is available but tinted lenses are sometimes used to enhance vision.

References
Article Title: 

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