cone dysfunction

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

Colorblindness-Achromatopsia 2

Clinical Characteristics
Ocular Features: 

Patients with this congenital, nonprogressive condition often have nystagmus as infants which may improve later. Eccentric fixation secondary to a small central scotoma is often present.  Visual acuity is 20/200 or worse.  Hyperopia is common.  Photophobia is extreme and vision under daylight conditions improves in dim light.  Patients are unable to distinguish any colors.  However, there is considerable variability in symptoms and some individuals retain some color perception and have better visual acuity (sometimes 20/80) than others suggesting some residual cone function.  The term ‘incomplete achromatopsia’ is sometimes applied to such cases but the molecular basis for this variation is unknown.  Optical coherence tomography reveals the central retina to be thinner than in normal controls.  The fundus appearance is normal, however.

ERG responses indicate an absence of cone function with no photopic responses. 

Systemic Features: 

There are no associated systemic abnormalities. 

Genetics

Mutations in CNGA3 account for approximately 25% of cases of achromatopsia.  ACHM2 is an autosomal recessive disorder caused by mutations in CNGA3 (2q11).  Mutations in this gene also have been found in rare patients with progressive cone dystrophies.  A clinically similar but genetically distinct disorder, ACHM3, results from mutations in CNGB3 (262300).  Mutations in GNAT2 (ACHM4; 139340) and PDE6C (ACHM5; 613093) also cause achromatopsia. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no treatment for the underlying condition but darkly tinted lenses can help in bright light.  Red contact lenses can alleviate photophobia and improve vision as well.  Low vision aids and vocational training can be of great benefit.  In spite of the poor vision, some patients may find that correction of the hyperopia enables them to see better. 

References
Article Title: 

Colorblindness-Achromatopsia 3

Clinical Characteristics
Ocular Features: 

Achromatopsia 3 is a congenital, nonprogressive form of blindness.  It is sometimes referred to as a rod monochromacy or stationary cone dystrophy.  Symptoms are usually present at birth or shortly thereafter.  Patients have pendular nystagmus, progressive lens opacities, severe photophobia, 'day' blindness, and, of course, color blindness.  High myopia is a feature in some populations.  Vision in daylight is often 20/200 or less but vision in dim light is somewhat better. The central scotoma often leads to eccentric fixation. 

The ERG shows a complete absence of cone function.  Optical coherence tomography has demonstrated a reduction in macular volume and thickness of the central retina, most marked in the foveolar region, presumably due in some way to the absence or dysfunction of cone photoreceptors.  Few histologic studies of adequately preserved retina have been reported but those available suggest dysmorphism of cones in the central macula.  The clinical appearance of the retina is usually normal. 

Systemic Features: 

There are no associated systemic abnormalities. 

Genetics

This is an autosomal recessive form of color blindness caused by mutations in CNGB3 (8q21-q22).  This mutation is found in nearly half of patients with achromatopsia.  It is especially common among Pingelapese islanders of the Pacific Caroline Islands where consanguinity occurs frequently due to the founder effect resulting from a 1775 typhoon.  A progressive cone dystrophy has been found in a few patients with mutations in this gene.

Other achromatopsia mutations are in CNGA3 causing ACHM2 (216900), GNAT2 causing ACHM4 (139340), and PDE6C causing ACHM5 (613093).   

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available but darkly tinted lenses can alleviate much of the photophobia.  Low vision aids and vocational training should be offered.  Refractive errors should, of course, be corrected and periodic examinations are especially important in children. 

References
Article Title: 

The cone dysfunction syndromes

Michaelides M, Hunt DM, Moore AT. The cone dysfunction syndromes. Br J Ophthalmol. 2004 Feb;88(2):291-7. Review.

PubMed ID: 
14736794
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