night blindness

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: 

Night Blindness, Congenital Stationary, CSNB2A

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. 

CSNB2A, or type 2A, is associated with myopia which ranges from mild to severe.  Residual rod function is diminished but not completely absent as suggested by the presence of small b-waves.  Cone function is impacted to some degree as well.  Nystagmus and strabismus are inconsistent findings.  Retinal pigmentation is usually normal in the X-linked forms. Visual acuity ranges from 20/30 to 20/200.  Night blindness is less severe in this form than in another X-linked CSNB (CSNB1A; 310500).  Mild dyschromatopsia is present in some patients but this is primarily a disease of rods.

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

Congenital stationary night blindness type 2A is an X-linked disorder caused by a mutation in the CACNA1F gene located at Xp11.23.  Only males are affected and carrier females do not have clinical disease.

This disorder is allelic to Aland Island Eye Disease (300600) from which it differs by an apparent lack of progressive myopia and the presence of a normal fovea.  Aland Island Eye Disease has foveal hypoplasia as well as iris and fundus hypopigmentation.

Another allelic disorder with mutations in CACNA1F is CORDX3 (300476), a cone-rod dystrophy.

Approximately 55% of X-linked CSNB are of this type while about 45% have another X-linked form known as CSNB1A, or type 1A (310500) secondary to a mutation at Xp11.4. 

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
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, CSNB1C

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 (CSNB1C) the b-wave responses are severely deficient (no scotopic response) and a-waves seem to be normal.  Some reduction in central acuity is common.  High myopia may be present together with nystagmus and strabismus.  In one family, hypoplastic discs and relative thinning of the inner nuclear layer were described in twin brothers.  ERG responses suggest loss of ON bipolar cell function similar to that found in patients with GRM6 mutations (CSNB1B; 257270).

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

CSNB1C, or type 1C, is one of four congenital nightblindness disorders with autosomal recessive inheritance.  It results from mutations in the TRPM1 (15q13-q14) gene which encodes for a calcium ion channel protein, part of the GRM6 signaling cascade.  

Other autosomal recessive CSNB disorders are: CSNB2B (610427), 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.  Refractive errors need to be corrected and low vision aids can be helpful for those with some loss of central acuity.

References
Article Title: 

Night Blindness, Congenital Stationary, CSNB1B

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, 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.

In this disorder (CSNB1B) the b-wave responses are severely deficient and a-waves seem to be normal.  Color vision is normal and refractive errors are unremarkable.  Visual acuity ranges from normal to a mild reduction (20/15-20/40).  One patient with 20/40 vision has been reported to have bone spicule pigment clumps in the midperiphery. Several patients with subnormal vision have been reported to have nystagmus.

Patients have a distinctive ERG pattern response to scotopic 15-Hz flicker stimuli that suggest that more than two rod neural pathways exist.

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

CSNB1B, or type 1B, is one of four CSNB disorders with autosomal recessive inheritance.  It is the result of mutations in the GRM6 gene (5q35) which lead to functional loss of the glutamate receptor.  

Other autosomal recessive CSNB disorders are: CSNB2B (610427), CSNB (unclassified; OMIM number pending), 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: 

Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram

Zeitz C, van Genderen M, Neidhardt J, Luhmann UF, Hoeben F, Forster U, Wycisk K, M?degty?degs G, Hoyng CB, Riemslag F, Meire F, Cremers FP, Berger W. Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4328-35.

PubMed ID: 
16249515

Night Blindness, Congenital Stationary, CSNB1A

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. 

CSNB1A, or type 1A, is associated with myopia which ranges from mild to severe.  Rod function is completely absent.  Nystagmus and strabismus are inconsistent findings.   Visual acuity ranges from 20/30 to 20/200.  Retinal pigmentation is usually normal in the X-linked forms.  Night blindness is more severe in this form than in another X-linked CSNB, type 2A (300071). 

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

Congenital stationary night blindness type 1A is an X-linked disorder caused by a mutation in the NYX gene located at Xp11.4.  Only males are affected and carrier females do not have clinical disease (although homozygous females with typical findings have been described).

Approximately 45% of X-linked CSNB are of this type while about 55% have another X-linked form known as CSNB2A, or type 2A (300071) resulting from a mutation at Xp11.23.  A single patient with high myopia absent night blindness with a mutation in the NYX gene has been reported.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
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: 

Fleck Retina of Kandori

Clinical Characteristics
Ocular Features: 

This disorder is usually included in listings of flecked retina syndrome but few reports exist.  Irregular flecks of variable size are distributed in the equator and posteriorly up to but excluding the macula.  Some disturbances of the RPE are seen and some degree of night blindness is usually present.  It seems to be a stable disorder.

Systemic Features: 

No systemic disease is associated.

Genetics

The genetic basis, if any, is unknown.

Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Flecked retina disorders

De Laey JJ. Flecked retina disorders. Bull Soc Belge Ophtalmol. 1993;249:11-22. Review.

PubMed ID: 
7952338

Nanophthalmos Plus Syndrome

Clinical Characteristics
Ocular Features: 

This is a recently described type of nanophthalmos with characteristic clinical features plus retinal degeneration and optic disc drusen.  Hyperopia is common and, like another recessive form of nanophthalmos (267760), patients have a progressive retinal dystrophy beginning with granular and mottled RPE changes and progressing to a bone spicule pattern resembling retinitis pigmentosa.  No synechiae have been reported in this syndrome however.  Macular retinoschisis and cystic changes with reduced foveal reflexes are commonly present.  The anterior chamber and angles are narrow but no reported cases have had angle closure glaucoma such as frequently occurs in other forms of nanophthalmos (267760, 609549, 600165, 611897).  Drusen of the optic nerve head can be demonstrated by ultrasound.  Scleral and choroidal thickening are usually present.  There is progressive deterioration of photoreceptors beginning with rod dysfunction and eventually involving cones as documented on ERG recordings.  Nyctalopia and visual difficulties begin in childhood and the visual field is concentrically constricted.  Visual acuity is in the range of 20/100 to 20/200.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This is an autosomal recessive disorder caused by mutations in the membrane frizzled-related protein coding gene MFRP (11q23) expressed in retinal tissue.  Both homozygous and compound heterozygous mutations have been described.  It seems to be allelic to another nanophthalmos condition without retinal pigmentary degeneration which is caused by different mutations in MFRP (NNO2 609549).  However, there is considerable clinical overlap of the several nanophthalmos conditions and it is possible that this is simply clinical heterogeneity within the same disease.

A syndromic form (MCOP5) of autosomal recessive microphthalmia with retinitis pigmentosa (611040) is also caused by mutations in MFRP and may be the same disorder.

For other forms of nanophthalmos see:  267760, 609549, 600165, 611897.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Angle closure glaucoma is a constant threat in some nanophthalmic conditions but has not been reported in this disorder.  Nevertheless, it may be prudent to consider prophylactic iridotomies in high risk cases.

References
Article Title: 

Nanophthalmos with Retinopathy

Clinical Characteristics
Ocular Features: 

This is a rare syndrome consisting of a pigmentary degeneration of the retina in association with nanophthalmos.  The globe is small with a thickened choroid and sclera and the macula becomes atrophic later in life. Some patients have cystic macular changes early without fluorescein leakage.  The anterior chamber is shallow, the angle is narrow, and the cornea may be small leading to angle closure glaucoma in most patients.  Extensive anterior and posterior synechiae can be seen.  The retina has a postequatorial bone spicule pattern of pigmentation with narrowing of arterial vessels.  Hyperopia is usually present and nightblindness may be noted in the first decade of life.  The ERG early shows loss of rod function and progression of the retinal disease subsequently leads to extinction of all rod and cone responses by midlife.  The EOG may be subnormal and visual fields are severely constricted.  Pallor and crowding of the optic nerve are common.  The vitreous may contain prominent fibrils and fine white granules.  Visual acuity is often 20/200 or worse.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This is likely an autosomal recessive disorder based on frequent parental consanguinity and sibships with multiple affected individuals of both sexes.  However, the first reported family in 1958 with 13 affected individuals in 4 generations suggested autosomal dominant inheritance. No molecular defect has been identified.

This may be the same disorder as microphthalmia with retinitis pigmentosa (611040) in which so far no molecular mutation has been identified. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Narrow angles with shallow anterior chamber depth should be treated with prophylactic iridotomies.

References
Article Title: 

Wagner Syndrome

Clinical Characteristics
Ocular Features: 

This is one of several hereditary vitreoretinal degenerative disorders in which vitreous degeneration occurs and the risk of retinal detachment is high (others being Goldmann-Favre [268100], Stickler [609508, 108300], and Marshall [154780] syndromes).  An optically empty central vitreous is a common feature in this heterogeneous group.  Other reported ocular findings in Wagner syndrome include perivascular sheathing and pigmentation, progressive chorioretinal dystrophy, ectopic fovea with pseudoexotropia, tractional retinal detachments, glaucoma (neovascular in some), and vitreous veils with fibrillar condensation.  Cataracts occur in virtually all patients over the age of 45 years.  The ERG in the majority of patients shows elevated rod and cone thresholds on dark adaptation (63%) and subnormal b-wave amplitudes (87%).  Mild difficulties in dim light are noted by some patients.  Visual acuities are highly variable ranging from normal in many patients to blindness in others.  Peripheral visual fields may be severely constricted.

Systemic Features: 

Cleft palate has been seen in some patients but these likely had Stickler syndrome (609508, 108300, 604841 ) since hearing loss along with other joint and skeletal manifestations are absent.  Further, cases reported to have Wagner syndrome with palatoschisis have not been genotyped so it is likely that they were misdiagnosed.

Genetics

Wagner syndrome results from a mutation in the VCAN gene encoding versican (5q14.3), a chondroitin sulfate proteoglycan-2 found in the vitreous among other tissues.  It is an autosomal dominant disorder.  It has been proposed that erosive vitreoretinopathy (ERVR) (143200) is allelic to Wagner’s syndrome but it may also simply be a variable expression of the same disorder.  Both map to 5q13-q14.  Overlapping of clinical signs and symptoms among hereditary disorders of vitreoretinal degeneration has created some confusion in their classification but this will hopefully be clarified as more families are genotyped.  Stickler syndrome (609508, 108300), for example, is known to be caused by a mutation in an entirely different gene (COL2A1) on a different chromosome.

Snowflake type vitreoretinal degeneration (193230), another autosomal dominant disorder, has a superficial resemblance but mutations in a different gene (KCNJ13) are responsible.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no therapy specifically for this disorder but the usual treatments for retinal detachments, cataract and glaucoma should be applied where appropriate.

References
Article Title: 

Abetalipoproteinemia

Clinical Characteristics
Ocular Features: 

The major ocular manifestations of abetalipoproteinemia are in the retina which develops diffuse and sometimes patchy pigmentary changes often called atypical retinitis pigmentosa.  In other cases the picture resembles retinitis punctata albescens with perivascular white spots in the peripheral retina.  Night blindness is an early and prominent symptom with abnormal dark adaptation thresholds evident before fundus pigment changes are seen.  The ERG shows loss of rod function before that of cone function.  The macula may or may not be affected while peripheral fields are often severely constricted.  Loss of photoreceptors occurs throughout life and visual fields show progressive constriction, sometimes with central sparing.  A single case of bilateral disc swelling in a 9 year-old girl has been reported.

Systemic Features: 

Celiac disease and steatorrhea due to a deficiency of circulating chylomicra underlie the malabsorption of vitamins A and E which is probably responsible for the majority of systemic manifestations.  Red blood cells have a peculiar burr-like morphology that has led to the designation 'acanthocytes'.  Liver failure and cirrhosis sometimes occur.  Plasma lipids are generally low including cholesterol, triglycerides, and beta lipoproteins.  Central and peripheral nerve demyelination occurs leading to a progressive ataxia and other neurological symptoms.

Genetics

This autosomal recessive disease seems to result from an inability to synthesize the apoB peptide that is a part of the LDL and VLDL.   A mutation in the MTP gene (4q22-q24) is responsible.  The gene is sometimes called MTTP as it codes for micosomal triglyceride transfer protein.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Treatment with vitamins A and E may be beneficial.  Cone function improves before rod function with massive doses of vitamin A but usually only after months of treatment.  It has been reported that Vitamin A alone without vitamin E is insufficient to arrest the retinal disease.

References
Article Title: 

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