WHAT IS ADOA
WHAT IS ADOA (AUTOSOMAL DOMINANT OPTIC ATROPHY)
ADOA is an autosomally inherited disease that affects the optic nerves. It causes reduced visual acuity and is a contributing factor of blindness, vision loss or impairment, beginning in childhood. This condition is due to mitochondrial dysfunction mediating the death of optic nerve fibers. Dominant optic atrophy was first described clinically by Batten in 1896 and named Kjer’s optic neuropathy in 1959 after Danish ophthalmologist Poul Kjer, who studied 19 families with the disease. (1)
Dominant Optic Atrophy is associated with mutation of the OPA1 gene (3) found on chromosome 3, region q28-qter. Also, five other chromosomal genes are described as causing optic atrophy: OPA2 (x-linked), OPA3 (dominant), OPA4 (dominant), OPA5 (dominant), OPA6 (recessive) (4), OPA7 & OPA8 (recessive). (9)
Autosomal Dominant Optic Atrophy can present clinically as an isolated bilateral optic neuropathy (non-syndromic form) or rather as a complicated phenotype with extra-ocular signs (syndromic form) peripheral neuropathy, deafness, cerebellar ataxia, spastic paraparesis and myopathy. (2) Dominant optic atrophy usually affects both eyes roughly symmetrically in a slowly progressive pattern of vision loss beginning in childhood and therefore is a contributor to childhood blindness. Vision testing will reveal scotomas (areas of impaired visual acuity) in the central visual fields with peripheral vision sparing and impaired color vision (color blindness). Visual acuity loss varies from mild to severe.
First signs of ADOA are typically present between four to six years of age, though presentation as early as one year of age has been reported. In some cases, Dominant Optic Atrophy may remain subclinical until early adulthood. Generally, the severity of the condition by adolescence reflects the overall level of visual function to be expected throughout most of the patient’s adult life. (5)
AUTOSOMAL DOMINANT OPTIC ATROPHY PLUS SYNDROME (ADOA PLUS)
Autosomal Dominant Optic Atrophy Plus Syndrome (ADOA Plus) is a variant of ADOA and accounts for approximately 20 percent of all ADOA cases. ADOA Plus is caused by mutations in the OPA1 gene. (10) Symptoms of ADOA Plus Syndrome typically start to occur within the first decade of life and are characterized by bilateral and symmetric progressive visual loss. Sensorineural deafness along with other extra-ocular manifestations may appear, such as chronic progressive external ophthalmoplegia, proximal myopathy, ataxia and axonal sensory motor polyneuropathy beginning in the second to third decades of life.
OPA1 GENE MUTATION
Optic atrophy type 1 (ADOA & ADOA Plus) is caused by mutations in the OPA1 gene. The protein produced from this gene is made in many types of cells and tissues throughout the body. The OPA1 protein is found inside mitochondria, which are the energy-producing centers of cells.
The vision problems experienced by people with optic atrophy type 1 are due to mitochondrial dysfunction, leading to the breakdown of structures that transmit visual information from the eyes to the brain. Affected individuals first experience a progressive loss of nerve cells within the retina, called retinal ganglion cells. The loss of these cells is followed by the degeneration (atrophy) of the optic nerve. The optic nerve is partly made up of specialized extensions of retinal ganglion cells called axons. When the retinal ganglion cells die, the optic nerve cannot transmit visual information to the brain normally. (6)
OTHER AUTOSOMAL DOMINANT OPTIC ATROPHY DISORDERS
Less common than OPA1 are two other Autosomal Dominant Disorders, OPA4 and OPA5. As with OPA1, vision loss in OPA4 and OPA5 generally starts in the first decade of life, however, it may not be evident until the third decade of life in some people. No systemic findings or abnormalities have been found in OPA4 or OPA5. (9)
AUTOSOMAL RECESSIVE OPTIC ATROPHY DISORDERS
OPA2 X-Linked (only affects males)
OPA3, OPA6, OPA7 and OPA8 (9)
Dominant optic atrophy is inherited in an autosomal dominant manner. That is, a heterozygous patient with the disease has a 50 percent chance of passing on the disease to offspring, assuming his/her partner does not have the disease.
Dominant Optic Atrophy has been estimated to be 1:50,000 with prevalence as high as 1:10,000 in the Danish population. (5)
1. Kjer, P (1959). "Infantile optic atrophy with dominant mode of inheritance: a clinical and genetic study of 19 Danish families.". Acta ophthalmologica. Supplementum 164 (Supp 54): 1–147. PMID 13660776.
2. Yu-Wai-Man, P; Griffiths, PG; Gorman, GS; Lourenco, CM; Wright, AF; Auer-Grumbach, M; Toscano, A; Musumeci, O; Valentino, ML; Caporali, L; Lamperti, C; Tallaksen, CM; Duffey, P; Miller, J; Whittaker, RG; Baker, MR; Jackson, MJ; Clarke, MP; Dhillon, B; Czermin, B; Stewart, JD; Hudson, G; Reynier, P; Bonneau, D; Marques W, Jr; Lenaers, G; McFarland, R; Taylor, RW; Turnbull, DM; Votruba, M; Zeviani, M; Carelli, V; Bindoff, LA; Horvath, R; Amati-Bonneau, P; Chinnery, PF (March 2010). "Multi-system neurological disease is common in patients with OPA1 mutations". Brain : a journal of neurology 133 (Pt 3): 771–86. doi:10.1093/brain/awq007. PMC 2842512. PMID 20157015.
3. Delettre, C; Lenaers, G; Griffoin, JM; Gigarel, N; Lorenzo, C; Belenguer, P; Pelloquin, L; Grosgeorge, J; Turc-Carel, C; Perret, E; Astarie-Dequeker, C; Lasquellec, L; Arnaud, B; Ducommun, B; Kaplan, J; Hamel, CP (October 2000). "Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy". Nature genetics 26 (2): 207–10. doi:10.1038/79936. PMID 11017079. Cite uses deprecated parameter |coauthors= (help)
4. OMIM: Optic Atrophy 1 OMIM 165500
5. Votruba, 1998.( Votruba; Moore, AT; Bhattacharya, SS (1998). "Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy". Journal of medical genetics 35 (10): 793–800. doi:10.1136/jmg.35.10.793. PMC 1051452. PMID 9783700.
6. Genetics Home Reference.com
7. Guy Lenaers et al. Dominant optic atrophy. Orphanet Journal of Rare Diseases. July 9, 2012; 7(46): Accessed 11/13/2013.)
8. Barboni P. et al. Idebenone treatment in patients with OPA1-mutant dominant optic atrophy. Brain. 2013; 136(Pt 2):e231:Accessed 11/13/2013.
The information presented is offered for educational and informational purposes only and should not be construed as personal medical advice. Please consult with a physician regarding personal medical questions and diagnosis.