Achromatopsia

Achromatopsia

A rare autosomal recessive retinal disorder characterized by color blindness, nystagmus, photophobia, and severely reduced visual acuity due to the absence or impairment of cone function.

Synonyms

• ACHM
• Complete or incomplete color blindness
• Pingelapese blindness
• Rod monochromacy
• Rod monochromatism
• Total color blindness

Incidence

How common is Achromatopsia

• 1-9 / 100000
• The prevalence is estimated to be 1/30,000-1/50,000 worldwide.

Inheritance

Autosomal recessive 

Age of Onset

• Infancy
• Neonatal

What are the symptoms of Achromatopsia?

• Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, and reduced or complete loss of color discrimination.
• Most individuals have complete ACHM, with total lack of function in all three types of cones.
• Rarely, individuals have incomplete ACHM, with similar, but generally less severe symptoms.

Very Common Symptoms

• Abnormality of refraction
• Color vision defect
• Color vision test abnormality 
• Inner retinal layer loss on macular OCT
• Monochromacy
• Pendular nystagmus
• Photophobia
• Undetectable light-adapted electroretinogram

Common Symptoms

• Absent foveal reflex
• Central scotoma
• Hypermetropia
• Hypoplasia of the fovea
• Myopia 
• Reduced visual acuity

Occasional Symptoms

• Abnormal macular morphology
• Abnormal pupillary light reflex
• Attenuation of retinal blood vessels
• Eccentric visual fixation
• Retinal pigment epithelial mottling

Rare Symptoms

• Retinal pigment epithelial atrophy 

What causes this condition?

• Five genes(GNAT2 (1p13), PDE6C (10q24), PDE6H (12p13), CNGA3 (2q11.2), and CNGB3 (8q21.3)) have been associated with ACHM, all encoding key components of the cone phototransduction cascade (G-protein GNAT2 > phosphodiesterase PDE6C/PDE6H > cyclic nucleotide gated channel CNGA3/CNGB3).
• Mutations in CNGB3 are the most prevalent, followed by CNGA3, while the others are rare causes of ACHM.

How is this condition diagnosed?

• The diagnosis of ACHM is based on clinical ophthalmological examination, psychophysical testing (i.e. color vision) and electrophysiological testing (electroretinography – ERG) where a loss of photopic but normal scotopic responses is observed.
• Optical coherence tomography shows progressive disruption and/or loss of the inner/outer segment junction of the photoreceptors and an attenuation of the retinal pigment epithelium (RPE) within the macular region.
• The diagnosis is verified by molecular genetic analysis of the causative genes.

Differential diagnosis

• Differential diagnosis includes blue cone monochromatism (BCM)
• Leber congenital amaurosis
• other cone dystrophies
• cerebral achromatopsia

Antenatal diagnosis

• Prenatal diagnosis may be offered by specialized laboratories to at-risk couples.

Genetic counseling

• ACHM is transmitted in an autosomal recessive manner.
• Carrier testing for family members at risk of mutations is possible once the disease-causing mutations have been identified in the family.
• Furthermore, genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.

How is Achromatopsia treated?

• There is no specific therapy available. Management is symptomatic and includes regular ophthalmological follow-up examination.
• Patients should be informed about the possibility of using filtering glasses or contact lenses (red tinted or brown) to reduce photophobia and to improve contrast sensitivity.
• Low-vision aids include high-powered magnifiers for reading.

What is the prognosis?

• ACHM is usually a stationary disease, yet macular degeneration can occur.