Genetic Testing: Is It for Me?

Some forms of small-fiber neuropathy (SFN) stem from mutations in genes necessary for proper form or function of peripheral nerves. These mutations are most often passed from parent to child, and are called inherited or genetic neuropathies. Some mutations affect proteins in the nerve cell membrane, leading to chemical changes in the cells that result in neuropathic pain. Other genetic defects cause the nerves to be overexcitable, so that the person feels pain despite lack of injury. In most cases of inherited neuropathy, symptoms start in childhood. Genetic testing may be appropriate for some patients if their symptoms or test results suggest they may have an inherited/genetic basis for their neuropathy.

Who should get genetic testing for SFN?

People who have been diagnosed with small-fiber neuropathy of unknown cause (“idiopathic SFN”) should first be screened for possible genetic disease using parent and family histories and prior test results. Genetic testing may be considered in adult patients with idiopathic SFN, and is indicated in all children who have idiopathic SFN, even if they don’t have a family history. More intensive testing, including genetic sequencing can be particularly beneficial in pediatric patients, people with a family history of SFN, and individuals with highly specific presentations of the disease.

What genetic test is best?

Genetic testing often involves the analysis of a select set of genetic mutations already known for their involvement in SFN, and whose identification can give your neurologist actionable information to steer your treatment. As we come to know more about the genes involved in SFN, those panels may be further expanded or narrowed. Other tests could involve analyzing the full genetic code of single or multiple genes, or the entire genome. These tests have the potential to identify new disease-causing mutations or genes, but are more expensive than existing standard genetic screens. The choice of genetic test is often driven by cost, and as genetic sequencing becomes more affordable, the relative values of sequencing single genes or gene panels versus the whole genome changes.

The results of genetic tests are not final. As our understanding of the genome and its variation evolves, so, too, will the tests themselves, and the meaning of the results. At best, the results will reflect what is known about genetic variants and SFN at the time of the test. Results that are unrevealing initially may later be found to be informative.

Ultimately, it is important to talk to your neurologist about whether genetic testing would be appropriate for you. Together, the two of you can decide if the possible benefits outweigh the cost of the testing.