Immunoglobulin A nephropathy (IgA nephropathy, or IgAN), also called Berger disease, is a type of kidney disease. It develops when an antibody called immunoglobulin A builds up in your kidneys. It can damage the small filters, known as glomeruli, inside your kidneys and lead to kidney failure over time.
Most cases of IgAN are not hereditary. But inherited genetics can play a significant role in IgAN. You may not develop the condition unless you inherit several risk genes and also encounter environmental triggers that affect how these genes work.
Most people diagnosed with IgA nephropathy have sporadic cases, which means that the condition develops without any clear family history. However, about 10% cases are familial, meaning they can run in families. This is most likely due to heritable genetic factors.
IgA nephropathy does not have a single-gene inheritance pattern, though. It is polygenic, meaning that several gene regions contribute to the development of the condition. This may explain why IgAN looks different in different people, with some people developing severe kidney damage while others develop mild disease.
Large-scale genome-wide association studies have identified 30 different regions in chromosomes that can increase the risk of IgAN. These include genetic mutations and variants in genes such as:
- IGAN1, a chromosomal region associated with susceptibility to IgAN
- SPRY2, which may affect critical immune pathways
- COL4A3 and COL4A5, which may weaken the kidneys’ filters
Epigenetic factors also play a role. These are behavioral and environmental factors—like illness, smoking, stress, and more—that “turn on” or “turn off” a gene’s expression or activity. Risk genes may not necessarily lead to IgAN unless or until you encounter one of these factors.
Studies suggest that the heritability of IgA nephropathy may range from 40-50%, which means that inherited genetics influence about half of the risk.
Moreover, heritability follows a pattern of autosomal dominant inheritance with incomplete penetrance.
Autosomal dominance means inheriting just one copy of the risk gene variant from either parent is enough to increase the risk of developing IgA nephropathy.
However, incomplete penetrance means that not everyone inheriting the risk gene variant develops the condition. This may be because environmental factors also play a role.
Along with genetic variants, a few other factors may also increase the risk. You may be more likely to develop IgAN if you:
- Are male
- Are 10-40 years old
- Have Pacific Island, Asian, or white European ancestry
- Have other medical conditions such as celiac disease, hepatitis, inflammatory bowel disease, or human immunodeficiency virus (HIV)
- Smoke
Although most cases of IgA nephropathy are not hereditary, about 10% of cases may be familial, which means the disease can pass on to your child if you have IgAN or carry risk genes. Because of incomplete penetrance, though, not every child who inherits the risk gene variants develops the condition.
Genetic counseling can be helpful for families with a history of IgA nephropathy or if you’re concerned about your child’s risk.
A genetic counselor can ask about your family history, look at your medical records and tests, and help clarify the chances of passing risk variants to children. They may also recommend genetic tests if you or your child is at risk of IgA nephropathy.
There is no single definitive test for this condition, since it likely develops due to a complex interaction of genetic and environmental factors. Counselors may recommend a combination of tests to determine the risk of developing IgAN. These tests may involve taking a sample of your blood, saliva, or cells swabbed from inside your cheek.
If you decide to go through with testing, a genetic counselor can help you interpret your results and help you decide what it means for your family, family planning, and next steps.
