Recently, scientists identified a fourth inheritance pattern through which a retinal
degeneration can be passed from one generation to the next, called digenic. So far,
only a few families affected by RP have been identified as digenic. Remember that
genes come in pairs. Although each pair of genes specifies one trait, each gene of the
pair may carry different instructions for that trait and each will influence how the trait is
actually produced in the body. In a digenic retinal degenerative disease, an affected
person has disease-causing mutations in two different gene pairs. Each of the gene
pairs has one normal gene and one altered gene. The two altered genes act together to
cause retinal degeneration, even though they lie on separate autosomes.
Carriers, individuals who have a mutation in one of the gene pairs but not the other, will
not be affected. When an unaffected carrier with a mutation in one gene has children
with an unaffected carrier with a mutation in the other gene the chances for having
children who are affected, unaffected or carriers resembles autosomal recessive
inheritance for the first two generations. There is 1 chance in 4, or 25 percent chance,
that both parents will pass on their altered gene copies, and therefore the disease, to
each child. There is 1 chance in 2, or a 50 percent chance, that each child will be a
carrier of one of the altered genes. If both parents pass on normal genes, the child wil
not be affected and will not be a carrier. There is 1 chance in 4, or a 25 percent chance
that each child will neither have retinal degeneration nor be a carrier (Figure 9).
Figure 9. Digenic retinal degeneratino with unaffected carrier parents.
Chromosome with
altered genes
Chromosomes with normal genes
From the second to third generations of digenic inheritance, there can be direct parent-
to-child transmission, similar to autosomal dominant inheritance. When a person
(whether male or female) with retinal degeneration due to these two altered genes ha
children with an unaffected non-carrier partner, there is 1 chance in 4, or 25 percent
chance, that the affected parent will pass on both altered gene copies, and therefore the
disease, to each child. There is 1 chance in 2, or a 50 percent chance, that each child
will be a carrier of one of the altered genes. And if both parents pass on normal genes,
the child will not be affected and will not be a carrier. There is 1 chance in 4, or a 25
percent chance, that each child will neither have retinal degeneration nor be a carrier
(Figure 10).
Figure 10. Digenic retinal degeneration with affected parent and affected parent.
Chromosome with
altered genes
Chromosomes with normal genes
Other combinations are more complicated to describe and very complete genetic
counseling will be needed.