Clinical Characteristics
Ocular Features
Two brothers have been reported with optic atrophy discovered as early as 3 and 5 years of age. Visual acuity in the 3rd decade of life was in the 20/200 range which was stable into the 4th and 5th decades. They also had red-green dyschromatopsia and thinning of the nerve fiber layer most pronounced in the temporal areas of the retina corresponding to the location of most marked pallor seen in the optic nerve. The nasal nerve fiber layer seemed to be preserved. Paracentral scotomas could be demonstrated.
Systemic Features
There were no systemic abnormalities reported in the brothers.
Genetics
Inheritance
OPA9 is caused by homozygous or compound heterozygous mutations in the ACO2 gene (22q13.2).
Mutations in ACO2 also cause infantile cerebellar retinal degeneration (ICRD) (614559) in which optic atrophy is a prominent feature associated with retinal degeneration, extensive neurodegenerative disease, and mitral valve dysfunction. The mode of inheritance is autosomal recessive.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.