Alex V. Levin
• Reduced or absent color discrimination with photophobia, reduced visual acuity, nystagmus, eccentric fixation, and small central scotoma all due to defective cone development
• May be divided into partial (incomplete) versus complete phenotypes
1 per 30,000 individuals (1)
• Consanguineous parents
• Family history
• Autosomal recessive inheritance
• ACHM1, gene unknown, chromosome, 14
• ACHM2, alpha subunit cone cGMP gated cation channel (CNGA3), 2q11
• ACHM3 (Pingelap variant), beta subunit cone cGMP gated cation channel (CNGB3), 8q21–22
• ACHM4 cone alpha subunit transducin (GNAT2),1p13
Reduced or absent protein expression in cone photoreceptors leads to inhibition of the normal phototransduction cascade and dysfunctional cone development (2)[B]
Mutated gene inherited from each parent
COMMONLY ASSOCIATED CONDITIONS
• Phenotypic heterogeneity includes cone dystrophy and cone-rod dystrophy
• Family history
– Typically presents in infancy as fine nystagmus with photophobia
– Stationary low visual acuity with poor color discrimination
– Children often referred to as “night owls” due to preference for night time activity and dim illumination
• Full ocular examination
– Nystagmus is fine, high frequency, often milder with age
– Assess visual function; best-corrected is typically 20/200 range
– Hyperopia may be present
– Photophobia on examination
– Minimal if any foveal hypoplasia or subtle pigmentary changes, most often normal appearance
– Fail color vision testing
DIAGNOSTIC TESTS & INTERPRETATION
Molecular genetic testing available
If nystagmus or presentation atypical, consider neuroimaging to rule out intracranial process
• Color vision tests show impaired color discrimination along protan, deutan, and tritan axes.
• Full-field ERG shows absent or severely diminished photopic response and typically normal scotopic response.
• Visual field testing may reveal small central scotoma.
• If able, OCT usually normal or shows macular thinning
• If able, multifocal ERG usually isoelectric
• Intravenous fluorescein angiography and fundus autofluorescence normal
• Reduced cone number
• Residual cones often abnormal in structure
• Incomplete achromatopsia is associated with partial cone function, resulting in some color discrimination, better visual acuity than in complete achromatopsia, and absence of photophobia.
– Blue-cone monochromatism (X-linked achromatopsia) has similar findings to achromatopsia and can be differentiated by Berson plates or by S-cone function on ERG (4)[C].
– Cone monochromatism, in which the L- or M-cones are functional.
– Cone dystrophy is typically associated with normal cone function at birth, with gradual deterioration and progression.
– Cone-rod dystrophy includes progressive rod dysfunction.
– Other causes of photophobia and nystagmus
– Foveal/macular hypoplasia (see chapter)
– Cerebral achromatopsia is associated with febrile illness or trauma.
• Dark or Corning filter sunglasses or red-tinted contact lenses (often not tolerated for abnormal appearance) reduce photophobia.
– Low vision aids
– Children may benefit from an Individualized Education Plan.
Issues for Referral
• Genetic counseling
– Low vision evaluation and support as indicated
Correction of refractive error
COMPLEMENTARY & ALTERNATIVE THERAPIES
None proven or indicated
Children should have an ophthalmic evaluation every 6–12 months to monitor refraction and function
• Genetic counseling
• Visual acuity is usually stable over time on later decades when slow degeneration may occur with natural age related loss of photoreceptors.
– Nystagmus and photophobia may improve slightly with age.
• Low vision
1. Rojas CV, Maria LS, Santos JL, et al. A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate. Eur J Hum Genet 2002;10:638–42.
2. Wissinger B, Gamer D, Jagle H, et al. CNGA3 mutations in hereditary cone photoreceptor disorders. Am J Hum Genet 2001;69:722–37.
3. Varsanyi B, Wissinger B, Kohl S, et al. Clinical and genetic features of Hungarian achromatopsia patients. Mol Vis 2005;11:996–1001.
4. Moskowitz A, Hansen RM, Akula JD, et al. Rod and rod-driven function in achromatopsia and blue cone monochromatism. Invest Ophthalmol Vis Sci 2009;50(2):950–8.