Achromatopsia

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

PDE6C, CNGB3, CNGA3, GNAT2, ATF6, PDE6H, RPGR, CNNM4, NBAS, HBB, CABP4, PLXNA2, CNTF, COASY, NYX, CC2D2A, FRMD7, STS, NR2E3, NOC2L, CRB1, OPN1SW, RHO, PAX6, CACNA1F, POC1B

Drugs

Adeno-associated viral vector serotype 8 containing the human CNGA3 gene under the control of a cone arrestin promoter, Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Adenovirus associated viral vector serotype 2/8 containing the human CNGA3 gene, Adenovirus associated viral vector serotype 8 containing the human CNGB3 gene, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins, Recombinant adeno-associated viral vector containing the human CNGB3 gene, Recombinant adeno-associated viral vector expressing the human CNGA3 gene

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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.

Epidemiology

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

Clinical description

ACHM 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.

Etiology

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.

Diagnostic methods

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 (see these terms), and 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.

Management and treatment

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.

Prognosis

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