Alex V. Levin
BASICS
DESCRIPTION
• 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
EPIDEMIOLOGY
Incidence
1 per 30,000 individuals (1)
RISK FACTORS
• Consanguineous parents
• Family history
Genetics
• 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
GENERAL PREVENTION
Genetic counseling
PATHOPHYSIOLOGY
Reduced or absent protein expression in cone photoreceptors leads to inhibition of the normal phototransduction cascade and dysfunctional cone development (2)[B]
ETIOLOGY
Mutated gene inherited from each parent
COMMONLY ASSOCIATED CONDITIONS
• None
• Phenotypic heterogeneity includes cone dystrophy and cone-rod dystrophy
DIAGNOSIS
HISTORY
• 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
PHYSICAL EXAM
• 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
Lab
Molecular genetic testing available
Imaging
If nystagmus or presentation atypical, consider neuroimaging to rule out intracranial process
Diagnostic Procedures/Other
• 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
Pathological Findings
• Reduced cone number
• Residual cones often abnormal in structure
DIFFERENTIAL DIAGNOSIS
• 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.
TREATMENT
MEDICATION
None
ADDITIONAL TREATMENT
General Measures
• 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
Additional Therapies
Correction of refractive error
COMPLEMENTARY & ALTERNATIVE THERAPIES
None proven or indicated
SURGERY/OTHER PROCEDURES
None
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Children should have an ophthalmic evaluation every 6–12 months to monitor refraction and function
PATIENT EDUCATION
• Genetic counseling
• www.dailystrength.org/c/Achromatopsia/support-group
• www.lowvision.org/achromatopsia_and_color_blindnes.htm
PROGNOSIS
• 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.
COMPLICATIONS
• Low vision
– Photophobia
REFERENCES
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.
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