Clinical Characteristics
Ocular Features
Low vision is noted in early childhood without systemic symptoms. The optic nerves appear pale (age of onset uncertain). The retinal nerve fiber layer may be reduced in thickness in all quadrants but only segmentally in some individuals. No VEP can be recorded. On brain MRI examination the optic tracts are thin. The appearance of the optic nerve is consistent with mild hypoplasia in some patients.
Systemic Features
Some patients have ataxia, cognitive deficits, and seizures. A brother and sister from a consanguineous Moroccan family and two unrelated individuals have been reported.
Genetics
Inheritance
This autosomal recessive condition is caused by homozygous or compound heterozygous mutations in the RTN4IP1 gene.
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.