Predictive and Presymptomatic Testing
Predictive and presymptomatic testing refers to tests performed on individuals who may be at risk for certain conditions based on their family history, genetics, or other factors, even though they do not currently exhibit symptoms of the disease. These tests help in assessing the likelihood of developing specific diseases in the future and can guide preventive measures, lifestyle changes, or early interventions. Below is a comprehensive list of tests under predictive and presymptomatic testing, divided by the type of condition they address:
1. Genetic Testing for Hereditary Conditions
Genetic tests analyze a person’s DNA to identify mutations or alterations that may increase the risk of developing certain hereditary diseases. These tests are often used in predictive and presymptomatic testing to evaluate an individual's predisposition to conditions that have a genetic basis.
a) Cancer-Related Genetic Testing
BRCA1/BRCA2 Testing: Identifies mutations in the BRCA1 and BRCA2 genes, which significantly increase the risk of breast, ovarian, and other cancers. Women with mutations in these genes may undergo increased surveillance, preventive mastectomies, or oophorectomies.
Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer): Testing for mutations in genes such as MLH1, MSH2, MSH6, and PMS2, which increase the risk of colorectal, endometrial, and other cancers.
Li-Fraumeni Syndrome: Testing for mutations in the TP53 gene, which predisposes individuals to various cancers, including sarcomas, breast cancer, and brain tumors.
Peutz-Jeghers Syndrome: Identifying mutations in the STK11 gene, which increases the risk of gastrointestinal cancers, particularly colorectal cancer.
b) Cardiovascular Disease
Familial Hypercholesterolemia (FH) Testing: Identifies mutations in genes like LDLR, APOB, or PCSK9, which increase cholesterol levels and the risk of early heart disease.
Long QT Syndrome Testing: Genetic testing for mutations in genes such as KCNQ1, KCNH2, and SCN5A, which can predispose individuals to arrhythmias and sudden cardiac death.
Familial Arrhythmias: Testing for inherited mutations that increase the risk of arrhythmias like Brugada syndrome or hypertrophic cardiomyopathy.
c) Neurodegenerative Diseases
Huntington’s Disease Testing: A presymptomatic test that detects the presence of CAG trinucleotide repeats in the HTT gene, which causes Huntington’s disease. The test can predict whether an individual will eventually develop the disorder, but it does not prevent its onset.
Alzheimer’s Disease Genetic Testing: Tests for mutations in the APOE gene (especially the APOE ε4 allele), which increases the risk of Alzheimer’s disease. However, the presence of this allele does not guarantee disease onset.
Parkinson’s Disease Genetic Testing: Identifies mutations in genes such as LRRK2, PARK7, PINK1, and SNCA, which are linked to hereditary forms of Parkinson’s disease.
2. Carrier Screening
Carrier screening is performed to identify individuals who carry one copy of a gene mutation that could cause a genetic disorder if inherited from both parents. Carrier testing is often done for recessive conditions and helps assess the risk of passing on inherited disorders to offspring.
a) Cystic Fibrosis (CF) Carrier Screening
Testing for mutations in the CFTR gene. Individuals who carry one mutated copy of the CFTR gene may pass on cystic fibrosis to their children if their partner is also a carrier.
b) Sickle Cell Anemia and Thalassemia Carrier Screening
Genetic tests to identify carriers of mutations in the HBB gene (for sickle cell anemia) or in the alpha or beta-globin genes (for thalassemia). Carrier screening is recommended for individuals of African, Mediterranean, or Asian descent.
c) Tay-Sachs Disease Carrier Screening
A test for carriers of mutations in the HEXA gene, which can cause Tay-Sachs disease, particularly among Ashkenazi Jewish populations.
d) Spinal Muscular Atrophy (SMA) Screening
Testing for mutations in the SMN1 gene, which leads to SMA, a neurodegenerative condition.
3. Testing for Metabolic Disorders
Predictive testing for metabolic disorders can assess the risk of conditions that affect the body's ability to process nutrients and other substances. Early detection allows for dietary modifications and early interventions to manage these disorders.
a) Phenylketonuria (PKU) Testing
A genetic test for mutations in the PAH gene, which can cause PKU, a metabolic disorder that affects the body's ability to break down phenylalanine. Untreated PKU can lead to intellectual disability and other neurological problems.
b) Maple Syrup Urine Disease (MSUD) Testing
A test for mutations in the BCKDHA, BCKDHB, or DBT genes that can lead to MSUD, a rare genetic disorder that affects the breakdown of certain amino acids and can lead to neurological damage.
4. Hearing Loss Genetic Testing
Some forms of hereditary hearing loss can be detected through genetic testing. These tests may help predict whether an individual will experience hearing loss and the age at which it may occur.
Connexin 26 (GJB2) Testing: A common genetic test to detect mutations in the GJB2 gene, which can lead to congenital hearing loss.
Usher Syndrome Testing: Genetic testing for mutations in various genes that cause Usher syndrome, a condition that combines hearing loss and progressive vision loss.
5. Prenatal and Early Childhood Testing
Prenatal and early childhood screening can help detect genetic and metabolic disorders before symptoms develop. These tests are often used for presymptomatic diagnosis in the fetus or newborn.
a) Amniocentesis and Chorionic Villus Sampling (CVS)
These are invasive tests that can be used to detect chromosomal abnormalities like Down syndrome, cystic fibrosis, and other genetic conditions during pregnancy.
b) Newborn Screening
A panel of tests conducted shortly after birth to detect metabolic, genetic, and endocrine disorders such as hypothyroidism, phenylketonuria, and sickle cell anemia.
6. Endocrine and Hormonal Predisposition Testing
Genetic and biochemical tests can identify individuals at risk of endocrine or hormonal disorders that could affect growth, metabolism, and development.
a) Congenital Adrenal Hyperplasia (CAH) Testing
Genetic testing to detect mutations in the CYP21A2 gene, which causes CAH, a condition affecting the adrenal glands and hormone production.
b) Diabetes Type 1 Risk Testing
Testing for specific genetic markers (such as the HLA-DR3 and HLA-DR4 alleles) associated with an increased risk of developing Type 1 diabetes.
7. Pharmacogenomics Testing
Pharmacogenomics is the study of how genes affect a person’s response to drugs. Predictive testing in pharmacogenomics can help guide the choice of medication and dosage based on genetic variants that influence drug metabolism, efficacy, and safety.
CYP450 Testing: Tests for variations in the CYP450 family of genes that affect the metabolism of drugs like warfarin, clopidogrel, and certain antidepressants. It helps predict drug responses and potential side effects.
Conclusion
Predictive and presymptomatic testing is a valuable tool in modern medicine that allows individuals to understand their genetic risks for various conditions, enabling earlier intervention, preventive care, and informed decisions about family planning. However, these tests also raise ethical, psychological, and social concerns, particularly in terms of potential discrimination, the impact of knowing one’s genetic risks, and the availability of appropriate counseling and support. These factors need careful consideration when deciding whether to undergo predictive and presymptomatic testing
