dyschromatopsia

Choroidal Dystrophy, Central Areolar 2

Clinical Characteristics
Ocular Features: 

Slowly progressive loss of vision is noted in the 4th and 6th decades with a mean age of onset at 46 years. ERG recordings suggest that the cone dysfunction is more severe and occurs earlier than rod deterioration.  Night blindness is usually not a major complaint.  A central scotoma is usually present but peripheral fields may be relatively intact.  Dyschromatopsia is often present.  Early in the disease the RPE may have a granular appearance but in later stages there is usually a sharply demarcated area of central RPE atrophy (sometimes called geographic atrophy).

Autoflourescence, pattern ERGs, and fine matrix mapping can reveal abnormalities before patients become symptomatic.

Systemic Features: 

No systemic features are known.

Genetics

This is a clinically and genetically heterozygous disorder.  Multiple mutations in the PRPH2 gene (6p21.1) have been identified in this condition.  Some of the clinical variation may be mutation-specific.

For a somewhat similar disorder see choroidal dystrophy, central areolar 1 (215500).

CACD is a genetically heterogeneous disorder with mutations in several genes responsible.  The majority of patients have one of several mutations in the PRPH2 gene (6p21.1-cen) and the inheritance pattern seems to be autosomal recessive (CACD2).  Other family trees in which mutations in PRPH2 were excluded suggest autosomal dominant inheritance (CACD3; 613144).   

The gene product of PRPH2 is important to the integrity and stability of the structures that contain light-sensitive pigments (e.g., photoreceptors). More than 100 mutations have been identified. The resultant phenotype can be highly variable, even within members of the same family but most affected individuals have some degree of pigmentary retinopathy within the macula or throughout the posterior pole.

The altered gene product resulting from mutations in PRPH2 often leads to symptoms beginning in midlife as a result of the slow degeneration of photoreceptors. This database contains at least 11 disorders in which PRPH2 mutations have been found.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No effective treatment is known.

References
Article Title: 

Central areolar choroidal dystrophy

Boon CJ, Klevering BJ, Cremers FP, Zonneveld-Vrieling MN, Theelen T, Den Hollander AI, Hoyng CB. Central areolar choroidal dystrophy. Ophthalmology. 2009 Apr;116(4):771-82, 782.e1.

PubMed ID: 
19243827

Retinitis Pigmentosa 79

Clinical Characteristics
Ocular Features: 

As in many autosomal dominant conditions, there is considerable clinical heterogeneity and even nonpenetrance among individuals.  Onset may consist of night blindness in early childhood but many patients are not symptomatic until the 6th or 7th decade of life.  The fundus signs are characteristic for retinitis pigmentosa with bone spicule pigmentation clumps, attenuated vessels, optic disc pallor, and peripheral retinal atrophy.  Visual fields are peripherally constricted to variable degrees.   Patches of chorioretinal "degeneration" and choroidal "sclerosis" have been described.  Photophobia, decreased central acuity, and some degree of dyschromatopsia have been reported.  Progression of symptoms is highly variable but central acuity is usually affected at some point.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This autosomal dominant type of retinitis pigmentosa seems to result from heterozygous mutations in the HK1 gene (10q22.1).  Its phenotype is nonpenetrant in some individuals.   

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment has been reported but low vision aids might be helpful especially for near vision.

References
Article Title: 

A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa

Sullivan LS, Koboldt DC, Bowne SJ, Lang S, Blanton SH, Cadena E, Avery CE, Lewis RA, Webb-Jones K, Wheaton DH, Birch DG, Coussa R, Ren H, Lopez I, Chakarova C, Koenekoop RK, Garcia CA, Fulton RS, Wilson RK, Weinstock GM, Daiger SP. A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2014 Sep 4;55(11):7147-58.

PubMed ID: 
25190649

Cone-Rod Dystrophy with Hearing Loss

Clinical Characteristics
Ocular Features: 

Patients note reduced vision in brightly-lit environments with onset in early adulthood and progressive central vision loss thereafter.   Nystagmus, photophobia, and dyschromatopsia may be present.  Younger individuals may complain of night blindness.  Visual fields show diffuse progressive suppression with relative sparing of selected areas such as the peripapillary region.  The ERG documents primary cone dystrophy but less involvement of the rods.  EOG testing in 4 patients showed reduced light-dark ratios.  Macular degeneration, attenuated vessels, subtle salt-and-pepper pigmentation, and spicular pigmentary deposits in the mid-periphery may be seen.

Systemic Features: 

The hearing loss is sensorineural in nature and can be progressive from its onset in childhood.

Genetics

This autosomal recessive disorder results from homozygous or compound heterozygous mutations in the CEPL78 (9q21.2) gene.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment for the basic condition has been reported.  Assistive hearing devices and tinted lenses could be helpful.

References
Article Title: 

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects

Nikopoulos K, Farinelli P, Giangreco B, Tsika C, Royer-Bertrand B, Mbefo MK, Bedoni N, Kjellstrom U, El Zaoui I, Di Gioia SA, Balzano S, Cisarova K, Messina A, Decembrini S, Plainis S, Blazaki SV, Khan MI, Micheal S, Boldt K, Ueffing M, Moulin AP, Cremers FP, Roepman R, Arsenijevic Y, Tsilimbaris MK, Andreasson S, Rivolta C. Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects. Am J Hum Genet. 2016 Sep 1;99(3):770-6.

PubMed ID: 
27588451

CEP78 is mutated in a distinct type of Usher syndrome

Fu Q, Xu M, Chen X, Sheng X, Yuan Z, Liu Y, Li H, Sun Z, Li H, Yang L, Wang K, Zhang F, Li Y, Zhao C, Sui R, Chen R. CEP78 is mutated in a distinct type of Usher syndrome. J Med Genet. 2016 Sep 14. pii: jmedgenet-2016-104166. doi: 10.1136/jmedgenet-2016-104166.

PubMed ID: 
27627988

Cone-Rod Dystrophy With Decreased Male Fertility

Clinical Characteristics
Ocular Features: 

Features of a cone dystrophy appear first followed by rod damage although the course of degeneration is variable.  Poor vision may be present in some individuals in the first years of life but has a later onset in others.  Evidence for rod dysfunction appears later in most patients.

A hyperfluorescent area centered on the fovea can often be seen although there may be patchy areas elsewhere in the fundus.  Foveal atrophy is present in individuals generally after the 5th decade of life. Full field ERG shows reduced or absent cone responses with variable rod responses with more pronounced changes in older individuals.  Variable pigmentation can be seen in the peripapillary area.

Systemic Features: 

The only systemic abnormality thus far identified is a reduction in sperm count and reduced motility.  The resulting loss of fertility, however, occurs only in male patients with truncating variants in TTLL5 and not in those with missense mutations according to the most recent studies.

Genetics

This autosomal recessive condition results from homozygous or compound heterozygous mutations in the TTLL5 gene (14q24.3).  TTLL5 is localized at the base of the spermatozoal axoneme and at the basal body of the cilia in photoreceptors.  

Interestingly, male mice with mutations in this gene have reductions in sperm motility with evident disruption in the formation of sperm tails.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility

Bedoni N, Haer-Wigman L, Vaclavik V, Tran HV, Farinelli P, Balzano S, Royer-Bertrand B, El-Asrag ME, Bonny O, Ikonomidis C, Litzistorf Y, Nikopoulos K, Yioti G, Stefaniotou M, McKibbin M, Ellingford J, Booth AP, Black G, Toomes C, Inglehearn CF, Hoyng CB, Bax N, Klaver CC, Thiadens AA, Murisier F, Schorderet DF, Ali M, Cremers FP, Andreasson S, Munier FL, Rivolta C. Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility. Hum Mol Genet. 2016 Aug 22. pii: ddw282. [Epub ahead of print].

PubMed ID: 
27554115

Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy

Sergouniotis PI, Chakarova C, Murphy C, Becker M, Lenassi E, Arno G, Lek M, MacArthur DG; UCL-Exomes Consortium, Bhattacharya SS, Moore AT, Holder GE, Robson AG, Wolfrum U, Webster AR, Plagnol V. Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy. Am J Hum Genet. 2014 May 1;94(5):760-9.

PubMed ID: 
244791901

Optic Atrophy 10

Clinical Characteristics
Ocular Features: 

Low vision is noted in early childhood without systemic symptoms.  The optic nerves appear pale (age of onset uncertain).  The retinal nerve fiber layer may be reduced in thickness in all quadrants but only segmentally in some individuals.  No VEP can be recorded.  On brain MRI examination the optic tracts are thin.  The appearance of the optic nerve is consistent with mild hypoplasia in some patients.

Systemic Features: 

Some patients have ataxia, cognitive deficits, and seizures.  A brother and sister from a consanguineous Moroccan family and two unrelated individuals have been reported.  

Genetics

This autosomal recessive condition is caused by homozygous or compound heterozygous mutations in the RTN4IP1 gene.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies

Angebault C, Guichet PO, Talmat-Amar Y, Charif M, Gerber S, Fares-Taie L, Gueguen N, Halloy F, Moore D, Amati-Bonneau P, Manes G, Hebrard M, Bocquet B, Quiles M, Piro-Megy C, Teigell M, Delettre C, Rossel M, Meunier I, Preising M, Lorenz B, Carelli V, Chinnery PF, Yu-Wai-Man P, Kaplan J, Roubertie A, Barakat A, Bonneau D, Reynier P, Rozet JM, Bomont P, Hamel CP, Lenaers G. Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies. Am J Hum Genet. 2015 Nov 5;97(5):754-60. 

PubMed ID: 
26593267

Macular Dystrophy with Central Cone Involvement

Clinical Characteristics
Ocular Features: 

This is primarily a cone dystrophy but there is evidence of some rod damage in older patients.  A mild decrease in central acuity is noted by individuals in the third to sixth decades.  Slight pigmentary changes and color vision abnormalities can be documented with the onset of these symptoms and a bull's eye maculopathy and severe atrophy of the central fovea may be present. An enlarging central scotoma with normal periphery can sometimes be identified.  Other patients have an atrophic appearance to the peripapillary area with a pale optic disc.  ERG responses to full-field testing are normal but multifocal studies reveal severely reduced central responses.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

Compound heterozygosity for a missense mutation and a nonsense mutation in the MFSD8 gene (4q28.2) has been found among members of a Dutch sibship suggesting autosomal recessive inheritance.       

The same mutant gene has been identified in some patients with late infantile or early juvenile onset lysosomal storage disease known as neuronal ceroid lipofuscinoses (610951) in which there may be optic atrophy, attenuated retinal vessels, a pigmentary retinopathy, and severe vision loss.   However, it is of note that no members of the Dutch family with the macular cone dystrophy described here had extraocular manifestations.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Retinal Dystrophy, Newfoundland Type

Clinical Characteristics
Ocular Features: 

There is considerable clinical heterogeneity, mostly age-dependent.  Night blindness can occur in early childhood but usually later even though scotopic responses can be undetectable in the first decade of life while photopic responses are reduced on the ERG at all ages.  Both rod and cone responses may be extinguished in later life.  Visual acuity can be decreased beginning in early childhood and legal blindness usually occurs by the second or third decade of life.  However, the loss of vision continues to progress and severe vision loss to finger-counting may be present in older individuals.  A scallop-bordered lacunar atrophy may be seen in the midperiphery.  The macula is only mildly involved by clinical examination although central retinal thinning is seen in all cases.  Dyschromatopsia is mild early and usually becomes more severe.  The visual fields are moderately to severely constricted although in younger individuals a typical ring scotoma is present.  The peripheral retina contains ‘white dots’ and often resembles the retinal changes seen in retinitis punctate albescens.

Systemic Features: 

None reported.

Genetics

Homozygous mutations in the RLBP1 gene (15q26.1) are responsible for this disorder.  Homozygous mutations in RLBP1 have also been found among patients with fundus albipunctatus (136880), retinitis punctata albescens, and in Bothnia type retinal dystrophy (607475),

NFRCD clinically resembles Bothnia type retinal dystrophy (607475) which likewise results from mutations in the RLBP1 gene but the maculae appear normal or have only a mild ‘beaten-bronze’ atrophy.

See Flecked Retina entry for somewhat similar conditions.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Retinal Dystrophy and Obesity

Clinical Characteristics
Ocular Features: 

The age of onset of symptoms is unknown but based on the report of a single family with three affected sibs, it may occur early in the second decade. Patients may note some loss of night vision and the visual fields are restricted.  The ERG responses are consistent with a generalized rod-cone dystrophy.  Fundoscopy reveals a generalized RPE atrophy together with arteriolar attenuation, peripheral pigmentary mottling and scattered white dots.  A nonspecific dyschromatopsia can be demonstrated but the fovea is relatively normal and central acuity is remarkably good.  Little is known about disease progression but an 18 year old male reported decreasing vision since the age of 11 years.  

Systemic Features: 

Obesity and a high BMI may be present.

Genetics

Homozygous mutations in the TUB gene (11p15) segregated with this disorder in a sibship from a consanguineous family.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Retinitis Pigmentosa 38

Clinical Characteristics
Ocular Features: 

This is a rare clinically heterogeneous condition in which both rods and cones functions are variably affected.  It is a progressive disorder with children often being aware of night vision difficulties during the latter half of the first decade of life.  Reduced vision is often present at this time as well and progressively deteriorates.  Visual fields are constricted to 20-30 degrees.  Rod responses may be nondetectable in the first decade.

Central vision is subnormal as early as childhood and progressively worsens with age.  Dyschromatopsia to some degree is often present early as well and some patients have a maculopathy with a bull’s eye pattern and thinning of the photoreceptor layer seen on OCT.  Attenuated retinal vessels, pale optic discs, and variable fundus pigmentary changes (including pigmentary mottling and bone spicules) have been seen.  The degree and course of the photoreceptor damage is variable leading some to propose that RP38 is primarily a cone-rod dystrophy.

Systemic Features: 

None

Genetics

This is an autosomal recessive disorder resulting from homozygous mutations in the MERTK gene (2q13).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported but young people especially could benefit from low vision aids and special education therapy.

References
Article Title: 

Retinal Cone Dystrophy 3B

Clinical Characteristics
Ocular Features: 

This is a degenerative disorder in which patients have a progressive deterioration of visual acuity and color vision.  Most patients have significant myopia.  Visual difficulties begin in early childhood with acuity of 20/100 or worse by the second decade of life.  Color vision deficits can be detected in the second decade but nyctalopia occurs later in young adults.  Photophobia is a prominent symptom.  The ERG shows reduced and delayed cone responses.  Rod responses to low intensity flashes are undetectable but increased stimulus intensity leads to an abrupt increase in amplitude, often exceeding the upper limits of normal.

The fundus appears normal in some patients but foveal or parafoveal atrophy, a macular bull’s eye, hyperfluorescence anomalies, and a generalized fine pigmentary retinopathy have been reported.  There may be some temporal pallor in the optic nerves.  Nystagmus and strabismus may be present.

Systemic Features: 

No systemic disease has been reported.

Genetics

This is an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in the KCNV2 gene (9p24.2).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment is available for this dystrophy.  Low vision aids and tinted lenses may be helpful.

References
Article Title: 

Pages

Subscribe to RSS - dyschromatopsia