colorblindness

Blue Cone Monochromacy

Clinical Characteristics
Ocular Features: 

This is usually a stationary cone dysfunction disorder in which the causative mechanism has yet to be worked out.  Typical patients have severe visual impairment from birth and some have pendular nystagmus and photophobia similar to other achromatopsia disorders.  Vision seems to be dependent solely on blue cones and rod photoreceptors.  The ERG always shows relatively normal rod function whereas the cones are usually dysfunctional. 

In some families, however, there is evidence of disease progression with macular RPE changes and myopia.  This has led to the designation of 'cone dystrophy 5' for such cases even though the mutation locus impacts the same cone opsin genes at Xq28 that are implicated in the more typical BCM phenotype.

Systemic Features: 

None.

Genetics

This is an X-linked recessive form of colorblindness in which DNA changes in the vicinity of Xq28 alters the red and green visual pigment cluster genes via recombination or point mutations.  Alternatively, the control locus adjacent to the cluster may be altered.  In either case, the result may be a loss of function of these genes leaving blue-cone monochromacy.

The mutation for cone dystrophy 5 maps to Xq26.1-qter but the locus encompasses the opsin gene complex at Xq28 as well. 

At least a quarter of individuals with blue cone monochromacy, however, do not have mutations in the vicinity of Xq28 suggesting that additional genetic heterogeneity remains.

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

Low vision aids can be helpful.  Tinted lenses for photophobia allow for greater visual comfort.  A magenta (mixture of red and blue) tint allows for best visual acuity since it protects the rods from saturation while allowing the blue cones to be maximally stimulated. 

References
Article Title: 

X-linked cone dystrophy caused by mutation of the red and green cone opsins

Gardner JC, Webb TR, Kanuga N, Robson AG, Holder GE, Stockman A, Ripamonti C, Ebenezer ND, Ogun O, Devery S, Wright GA, Maher ER, Cheetham ME, Moore AT, Michaelides M, Hardcastle AJ. X-linked cone dystrophy caused by mutation of the red and green cone opsins. Am J Hum Genet. 2010 Jul 9;87(1):26-39.

PubMed ID: 
20579627

Genetic heterogeneity among blue-cone monochromats

Nathans J, Maumenee IH, Zrenner E, Sadowski B, Sharpe LT, Lewis RA, Hansen E, Rosenberg T, Schwartz M, Heckenlively JR, et al. Genetic heterogeneity among blue-cone monochromats. Am J Hum Genet. 1993 Nov;53(5):987-1000.

PubMed ID: 
8213841

Molecular genetics of human blue cone monochromacy

Nathans J, Davenport CM, Maumenee IH, Lewis RA, Hejtmancik JF, Litt M, Lovrien E, Weleber R, Bachynski B, Zwas F, et al. Molecular genetics of human blue cone monochromacy. Science. 1989 Aug 25;245(4920):831-8.

PubMed ID: 
2788922

Colorblindness-Achromatopsia 5

Clinical Characteristics
Ocular Features: 

Poor visual acuity and congenital nystagmus are characteristic of ACHM5 and may be seen in infancy.  Vision loss can be progressive for those who have a milder form of colorblindness or incomplete achromatopsia.  Such patients have a somewhat later onset and may not have nystagmus or photophobia.  Cone responses are usually absent in the ERG whereas rod responses are often normal.  However, in the incomplete form there may be reduced but measureable cone responses.  There may be some reduction in rod responses with disease progression.  Myopia has been found in some patients.  Atrophy of the RPE in the posterior pole characteristic of progressive cone dystrophies may be seen. 

Systemic Features: 

No systemic abnormalities are found in this disorder. 

Genetics

This is an autosomal recessive disorder resulting from mutations in the PDE6C gene located at 10q24.  This condition is sometimes called cone dystrophy 4.

Other forms of achromatopsia are ACHM3 caused by mutations in CNGB3 (262300), ACHM2 caused by mutations in CNGA3 (216900), and ACHM4 by mutations in GNAT2 (139340).

 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no treatment for the cone dystrophy but dark glasses and red colored contact lenses are helpful in reducing the photophobia and can improve acuity to some extent.  Low vision aids can also be helpful. 

References
Article Title: 

A Nonsense Mutation in PDE6H Causes Autosomal-Recessive Incomplete Achromatopsia

Kohl S, Coppieters F, Meire F, Schaich S, Roosing S, Brennenstuhl C, Bolz S, van Genderen MM, Riemslag FC; the European Retinal Disease Consortium, Lukowski R, den Hollander AI, Cremers FP, De Baere E, Hoyng CB, Wissinger B. A Nonsense Mutation in PDE6H Causes Autosomal-Recessive Incomplete Achromatopsia. Am J Hum Genet. 2012 Sep 7; 91(3) :527-32.

PubMed ID: 
22901948

Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders

Thiadens AA, den Hollander AI, Roosing S, Nabuurs SB, Zekveld-Vroon RC, Collin RW, De Baere E, Koenekoop RK, van Schooneveld MJ, Strom TM, van Lith-Verhoeven JJ, Lotery AJ, van Moll-Ramirez N, Leroy BP, van den Born LI, Hoyng CB, Cremers FP, Klaver CC. Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders. Am J Hum Genet. 2009 Aug;85(2):240-7.

PubMed ID: 
19615668

Colorblindness-Achromatopsia 4

Clinical Characteristics
Ocular Features: 

The ocular phenotype in ACHM4 is similar to that of other forms of achromatopsia.  Nystagmus, poor visual acuity, photophobia, and defects in color vision are usually present.  Some subjects, however, retain some color discrimination, a condition referred to as incomplete achromatopsia.  The ERG documents the absence of cone function but normal rod responses.  The retina appears normal clinically.

Few families have been reported and the complete phenotype remains undocumented.  For example, it has been reported that visual acuity weakens with age in some patients although it is uncertain if this is true of all cases. 

Systemic Features: 

No systemic abnormalities are associated. 

Genetics

This is an autosomal recessive disorder caused by mutations in GNAT2 located at 1p13.  These mutations account for less than 2% of achromatopsia cases.  The majority are caused by mutations in CNGA3 (25%), responsible for ACHM2 (216900) and CNGB3 (50%), causing ACHM3 (262300).  Mutations in PDE6C (613093 ) causing ACHM5 are responsible for less than 2%. No doubt others will be found as many cases do not have mutations in these genes. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for this disorder but tinted lenses and low vision aids can be helpful.  Red contact lenses can reduce the photophobia and may improve vision. 

References
Article Title: 
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