The Three Major Inheritance Patterns

Most retinal degenerative diseases — including retinitis pigmentosa, Stargardt disease, and Usher syndrome — are inherited. They are caused primarily by genetic variations that are passed down from one or both parents, through one of the three inheritance patterns reviewed in this article. (The following discussion on inheritance patterns is not relevant for age-related macular degeneration (AMD), because risk of AMD is associated with a complex combination of genetic and lifestyle factors.) 

Everyone has about 25,000 pairs of genes. Genes play a major role in determining who we are — our height, hair color, risk for some diseases, and much more. We all have many changes, defects, and alterations in our genes. Most of these variations do not affect who we are or our health or well being. However, some genetic variations, also called mutations, can cause problems. Some mutations inevitably lead to diseases, including retinal degenerative diseases.

Genes are wrapped in structures called chromosomes, and humans normally have 23 pairs of chromosomes. We inherit one of each chromosome (and the genes on each chromosome) from our mother and father. Chromosomal pairs 1 through 22 are known as autosomal (non-sex) chromosomes. The chromosomes on pair 23 are known as the sex chromosomes, because one of their functions is to determine what sex we will be. 

 

 

Some people are carriers of disease, meaning they themselves don’t have the condition, but can pass it along to their children. When someone has the disease and shows symptoms of it, they are known as being affected.

 

Autosomal Recessive Inheritance
To be affected by a recessive disease, a child must inherit a mutated copy of the gene from both parents. With recessive disease, each parent has one mutated copy and one normal copy of the relevant gene. Because each parent has only one mutated copy of the gene, they are each unaffected carriers of the condition. However, they usually have no idea that they are a carrier, because they have no related vision problems. 

If their child inherits only one mutated gene from one parent, then the child will be an unaffected carrier of the disease and won’t experience any problems.

If their child inherits a mutated copy from each parent, then the child will develop the disease and associated vision loss.

 

With recessive disease, there is a one in four (25 percent) chance that the child will be affected, and a two in four (50 percent) chance that they will be an unaffected carrier. There is also a one in four (25 percent) chance they will be neither a carrier nor affected.   

Recessive diseases are more likely to come as a surprise to a family, because parents of an affected child are unaffected carriers, and the disease may not have shown up for several generations, if at all.

Examples of recessive retinal degenerative diseases include: retinitis pigmentosa (some forms); Stargardt disease (most forms), Leber congenital amaurosis (most forms), and Usher syndrome.

 

 

To be affected by an autosomal dominant disease, a child receives one copy of a mutated gene from an affected parent. It is likely that the affected parent knows they have the disease, or at least has related symptoms. The other parent is neither affected nor a carrier. 

With dominant diseases, there is a one in two (50 percent) chance that a child will receive the mutated gene and be affected by the disease, and a one in two (50 percent) chance the child will not receive the mutation at all. 

Dominant diseases tend to show up in several generations of a family, and many family members are affected. 

Examples of dominant retinal degenerative diseases include: retinitis pigmentosa (some forms) and macular degeneration (some forms of early onset disease). 

 

Inheritance patterns for X-linked diseases are more complex than the other inheritance patterns, because the gender of both the parents and their children determine if the disease will be passed down to the children.

Here’s some background on the last pair of chromosomes, the sex chromosomes, to help explain the inheritance of X-linked disease. Chromosomes on the last pair are either X or Y. All women have two X chromosomes. All men have one X and one Y. When a man and a woman have a child, the woman will always pass along an X chromosome. The man will pass along either an X or a Y. If he passes along an X, the child will have two X chromosomes and be a girl. If he passes a Y, the child will have an X and a Y and be a boy.

X-linked diseases are passed along on the X chromosome. Generally speaking, males are affected by X-linked diseases, and women are unaffected carriers. Carrier mothers pass X-linked diseases down to their sons. 

If an X-linked carrier mother has a son, there is a one in two (50 percent) chance that the son will be affected, and a 50 percent chance the son will not receive the mutated gene at all.

If an X-linked carrier mother has a daughter, there is a one in two (50 percent) chance that the daughter will be a carrier, and a 50 percent chance the daughter will not receive the mutated gene at all.

While females are usually unaffected carriers of X-linked retinal diseases, researchers have found that they can sometimes have mild vision loss, or in rarer cases, severe vision loss. Researchers are working to better determine the percentage of female carriers of X-linked retinal diseases that experience some vision loss, and the factors (environmental and/or genetic) that influence the extent of their vision loss.     

Examples of X-linked retinal degenerative diseases include: retinitis pigmentosa (some forms), choroideremia, and retinoschisis.