What is Autosomal Dominant Optic Atrophy?
Autosomal dominant optic atrophy (ADOA) is a rare genetic disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Approximately 80% of patients experience symptoms before age 10, typically beginning between the ages of 4 and 6.1,4
Although it is a rare disease, ADOA is the most common inherited optic nerve disorder seen in clinical practice.
ADOA was first described by two British ophthalmologists, Frederick Batten and Simeon Snell, at the end of the 19th century. It was later named Kjer’s optic neuropathy, after Danish ophthalmologist Poul Kjer, who studied 19 families with the disease in the 1950s.3
Symptoms and Effects
What are the symptoms and effects?
Characteristic features of ADOA include central field defects and reduced color vision.1 The severity of the disease can vary greatly – even within families – with visual acuity and rate of vision loss being difficult to predict.1,2,5,6 Many children progress to blindness.1,2,3 About half of people with dominant optic atrophy do not meet driving standards and up to 46% are registered as legally blind.1
Approximately 20% of patients have a more severe form called ADOA “plus” syndrome. In addition to vision loss, these patients experience significant non-visual effects such as permanent hearing loss or other more severe conditions affecting the body’s nervous system and skeletal muscles.5
Cause and Diagnosis
What is the Cause?
Approximately 65-90% of dominant optic atrophy cases are caused by a mutation of the OPA1 gene.6 More than 400 different OPA1 mutations have been reported in people diagnosed with dominant optic atrophy.7
Most mutations in the OPA1 gene result in a severe decrease – up to 50% – of the normal amount of OPA1 protein. This is known as a haploinsufficiency because there is only one functional copy of the gene and is the leading cause of ADOA.5,6
When a person with a mutation of the OPA1 gene has children, each child has a 50% chance of inheriting the mutation, and it affects males and females equally. The mutation can occur spontaneously (de novo).1,3
How is ADOA Diagnosed?
Most patients are diagnosed when entering school or only incidentally during the examination of other affected members of the family.3 Diagnosis is usually made by an ophthalmologist based on a combination of family history and clinical findings, such as the presence of optic disc pallor, an abnormal coloration of the optic disc. Genetic testing is typically performed to confirm diagnosis.
- Yu-Wai-Man P et al. The Prevalence and Natural History of Dominant Optic Atrophy Due to OPA1 Mutations. Ophthalmology. 2010 August; 117(8): 1538-1546.
- Yu-Wai-Man P, Chinnery PF. Dominant Optic Atrophy: Novel OPA1 Mutations and Revised Prevalence Estimates. Ophthalmology.Vol. 120, Number 8, August 2013: 1712-1712.
- P. Amati-Bonneau P et al. OPA1-associated disorders: phenotypes and pathophysiology. The International Journal of Biochemistry & Cell Biology 41, 1855-1865 (2009).
- “What is ADOA?” Autosomal Dominant Optic Atrophy Association. Accessed May 6, 2020, from https://www.adoaa.org/what-is-adoa.
- Lenaers G, Hamel C, Delettre C, et al. Dominant optic atrophy. Orphanet J Rare Dis 7, 46 (2012).
- Chun BY and Rizzo JF III. Dominant optic atrophy: updates on the pathophysiology and clinical manifestations of optic atrophy 1 mutation. Curr Opin Ophthalmol 2016; 27:475-480.
- Le Roux B, Lenaers G, Zanlonghi X et al. OPA1: 516 unique variants and 831 patients registered in an updated centralized Variome database. Orphanet J Rare Dis 14, 214 (2019).
Autosomal Dominant Optic Atrophy (ADOA): A Severe, Progressive Optic Nerve Disorder
Sources: Yu-Wai-Man P et al. Ophthalmology, 2010; Yu-Wai-Man P, Chinnery PF. Ophthalmology, 2013; P. Amati-Bonneau P et al. The International Journal of Biochemistry & Cell Biology, 2009; Lenaers G, Hamel C, Delettre C, et al. Orphanet J Rare Dis, 2012; Chun BY and Rizzo JF III. Curr Opin Ophthalmol, 2016; Le Roux B, Lenaers G, Zanlonghi X et al. Orphanet J Rare Dis, 2019; “What is ADOA?” Autosomal Dominant Optic Atrophy Association. Accessed May 6, 2020, from adoaa.org/what-is-adoa;