New Delhi: When most people think about genetic diseases, they imagine a simple connection: one faulty gene causes one specific illness. In reality, genetics is far more complex. Doctors and researchers are increasingly discovering that the same gene can lead to very different health outcomes in different people. This highlights why personalized medicine, which tailors care to each individual, is becoming essential.
In an interaction with News9Live, Dr Aparna Ganapathy – Director of Medical Genetics & Genomics at Strand Life Sciences, explained how rare diseases look different, and the role of genetics in triggering variations.
Why rare diseases can look so different
Advances in DNA sequencing have revealed something surprising—not everyone with the same genetic change develops the same disease, or any disease at all. Some people may develop symptoms early in life, while others remain healthy for decades. Some experience mild effects, while others face severe complications. In rare cases, changes in the same gene can even lead to entirely different disorders. This is known as phenotypic diversity. Simply put, it means that a person’s genes do not tell the whole story. Many other factors influence how a condition develops and progresses.
What drives these differences?
Several biological and environmental factors help explain why rare genetic disorders can look so different from person to person.
- One gene, many roles: Many genes perform multiple jobs in the body. When something goes wrong with such a gene, it can affect several organs at once.
- Different mutations, different effects: Not all genetic changes are equal. Some completely disable a gene, while others only partially reduce its function.
- Other genes can play a role: Each person’s DNA is unique. Additional genes can either worsen or soften the impact of a disease-causing mutation.
- Gene regulation and epigenetics: Genes can be turned up or down like volume controls. Chemical changes that affect how genes are switched on or off can influence when and where symptoms appear, even if the underlying DNA sequence is the same.
- Lifestyle and environment: Factors such as nutrition, infections, physical activity, and exposure to pollutants can also shape disease outcomes.
Some real-world examples of diverse symptoms seen in rare diseases
The effects of this diversity can be seen across many rare conditions:
- Cystic fibrosis-related disorders: Changes in the same gene (CFTR) can cause classic cystic fibrosis with severe lung disease in some patients, while others may experience milder breathing problems or infertility without major lung symptoms.
- Neurological conditions: Mutations in certain epilepsy-related genes, such as SCN1A, can produce mild childhood seizures in some people, while others develop severe forms of epilepsy with developmental challenges.
- Muscle and heart disorders: Mutations in specific genes, such as the TTR gene, may cause muscle weakness in one family member and heart rhythm problems in another.
- Differences even within families: Perhaps most striking is that members of the same family who carry the same genetic mutation may show very different symptoms.
Why this matters for patients and doctors
Understanding phenotypic diversity has important implications for healthcare:
- Better diagnosis: Rare diseases are often difficult to diagnose because symptoms don’t always match textbook descriptions. Broader genetic testing approaches now help doctors identify unusual or unexpected disease presentations.
- More accurate interpretation of genetic results: Finding a genetic variant does not automatically predict how severe a disease will be. Doctors must consider the type of mutation, the patient’s symptoms, family history, and other biological factors.
- Improved genetic counseling: Families want to know what a diagnosis means for the future. Because outcomes can vary widely, healthcare providers must explain uncertainty and the range of possible scenarios.
- Personalised treatment approaches: As targeted therapies become more common, understanding how different genetic changes affect disease pathways helps doctors select the most appropriate treatments and design better clinical trials.
As genomic medicine continues to advance, recognising the many stories that can emerge from a single gene will be key to delivering better care and brighter futures for people affected by rare diseases.