Rare diseases often present a complex diagnostic challenge, leaving individuals and families in prolonged uncertainty. Their varied and subtle symptoms can make identifying the underlying cause difficult for healthcare providers. Genetic testing offers a powerful tool, providing a path to understanding the biological basis of these conditions and offering clarity for those affected.
Understanding Rare Diseases and Genetic Testing
A rare disease is defined by its prevalence within a population. In the United States, a condition is considered rare if it affects fewer than 200,000 people, as established by the Orphan Drug Act. Thousands of known rare diseases have a genetic origin, caused by changes in an individual’s genetic material.
Genetic testing involves analyzing an individual’s biological samples to identify specific changes in their genes, chromosomes, proteins, or metabolites. This analysis can detect variations in DNA sequences, RNA expression alterations, or chromosome structure abnormalities. The goal is to pinpoint genetic mutations or other changes linked to a health condition, making genetic testing uniquely suited to uncover the underlying mechanisms of rare diseases.
When and Why Genetic Testing is Recommended
Genetic testing for rare diseases is recommended to provide definitive answers. A primary reason is to conclude a prolonged diagnostic journey for individuals with undiagnosed conditions, helping identify the specific genetic cause of their symptoms. Testing can also confirm a suspected diagnosis, providing certainty where clinical signs alone are not conclusive.
Another important application involves guiding treatment decisions, particularly through an approach known as pharmacogenomics. This field examines how an individual’s genetic makeup influences their response to certain medications, allowing for more personalized and effective therapeutic strategies. Testing can also offer insights into the likely progression of a disease, aiding in prognosis and long-term management planning. For families, genetic testing can inform reproductive choices through carrier screening or prenatal diagnosis, especially when a familial genetic condition is known.
The Genetic Testing Process
Rare disease genetic testing begins with a consultation involving a healthcare provider or genetic counselor. During this meeting, the professional reviews the individual’s medical history, family history, and symptoms to determine the most appropriate genetic test. This discussion helps set expectations and address questions about the process.
Following the consultation, a biological sample is collected from the individual. Common types include a blood draw or a saliva sample. In some cases, other tissue samples may be required depending on the specific test being performed.
Once collected, the sample is sent to a specialized laboratory for analysis. Methodologies range from single gene testing, which looks for changes in a specific gene, to gene panels that examine multiple genes. More comprehensive approaches include whole exome sequencing (WES), analyzing protein-coding regions, and whole genome sequencing (WGS), examining the entire DNA sequence. The laboratory processes the sample, extracts genetic material, and uses advanced techniques to identify variations. Results can vary from several weeks to a few months, depending on test complexity.
Interpreting and Using Test Results
Once genetic test results are available, a genetic counselor communicates and explains them. Results fall into three main categories. A “positive” result indicates a pathogenic variant, or a genetic change known to cause disease, has been identified.
Conversely, a “negative” result means no pathogenic variant linked to the suspected condition was found. The third category includes “variants of uncertain significance” (VUS), genetic changes whose impact on health is not yet fully understood. Genetic counselors interpret these complex findings, explaining their implications for diagnosis, treatment options, and disease management. They also discuss the implications for family members, including inheritance risk. These results can guide decisions regarding targeted therapies, clinical trial participation, or informed reproductive planning.