Prenatal Screening and Diagnosis

• Gametogenesis is the process where the body produces sperm in males and eggs in females for reproduction.
• Spermatogenesis is the formation of sperm in the testes.
• Oogenesis is the formation of eggs in the ovaries.
• Mistakes during gametogenesis can lead to fertility problems, pregnancy issues, or birth defects.

Potential Gametogenesis Errors

• There are different types of errors that can occur during gametogenesis.

Chromosomal Errors

• These involve having too many or too few chromosomes.
• Non-disjunction is the failure of chromosomes to separate properly and can occur during sperm or egg formation.
• This can cause genetic disorders:
  • Down syndrome (Trisomy 21) results when a baby has three copies of chromosome 21 instead of two.
  • Turner syndrome (45, X) results when a female is born with only one X chromosome instead of two.
  • Polyploidy is when a baby receives extra chromosome sets and this condition is usually fatal; for example, triploidy (69 chromosomes) instead of the normal 46.

Structural Chromosomal Errors

• These involve the breaking or rearrangement of chromosomes.
• Translocation happens when a piece of one chromosome moves to another and can lead to infertility or miscarriage.
• Inversion occurs when a chromosome piece flips around, potentially affecting genes and causing birth defects.

Gene Mutations

• These involve small DNA changes.
• Point mutations are small errors in DNA that can cause diseases like cystic fibrosis or sickle cell anemia.
• Deletions are when part of a chromosome is missing, potentially resulting in conditions like Cri-du-chat syndrome.

Errors During Sperm or Egg Development

• Premature egg maturation: eggs develop too early and don't function correctly.
• Spermatogenic arrest: sperm stops developing, leading to male infertility.

Epigenetic Errors

• These involve incorrect gene switching in which genes should turn on or off at the appropriate time.
• Disorders like Angelman syndrome (delayed development) and Prader-Willi syndrome (growth and eating problems) can occur if this process goes wrong.

Causes of Gametogenesis Errors

• Errors can arise from various factors.
• Genetic factors: a parent can pass a genetic condition to their child.
• Environmental factors: radiation, toxins, and drugs can damage sperm or eggs.
• Aging plays a role, with older mothers (above 35) facing a higher risk of trisomies like Down syndrome, and older fathers potentially having sperm mutations that increase the risk of genetic disorders.
• Mistakes in DNA mixing (recombination errors) during the combination of DNA from the mother and father can lead to missing or extra genes.

Impact on Pregnancy and Babies

• Infertility can occur if there are sperm or egg problems preventing pregnancy.
• Miscarriages can result from chromosomal abnormalities causing pregnancy loss.
• Birth defects such as Down syndrome or Turner syndrome can occur.

Detection Methods

• Doctors use genetic tests to check for chromosome or gene problems before or during pregnancy.
• Karyotyping is a chromosome picture test and finds extra/missing chromosomes like in Down syndrome.
  • This involves taking a blood sample, staining the chromosomes, and examining them under a microscope for abnormalities.
• FISH (Fluorescent DNA Test for Small Errors) finds tiny deletions or rearrangements in chromosomes.
  • Fluorescent probes stick to specific genes in a sample, and a microscope reveals glowing spots if there's a problem.
  • FISH is used for conditions like DiGeorge syndrome or trisomies (Down, Edwards, Patau).
• PGD (Preimplantation Genetic Diagnosis - IVF Screening) checks embryos before IVF implantation for genetic problems.
  • Eggs are fertilized in a lab, and a tiny cell from each embryo is tested.
  • Only healthy embryos are implanted into the mother, preventing conditions like Down syndrome, cystic fibrosis, or other inherited disorders.

Prevention Strategies

• Genetic counseling helps parents understand risks before pregnancy.
• Healthy lifestyle choices, such as avoiding radiation, toxins, smoking, and alcohol, help protect sperm/eggs.
• Folic acid supplements prevent neural tube defects, such as spina bifida.
• Scientists are working on gene editing (CRISPR) to fix genetic errors.

Maternal Screening

• Maternal screening is important for detecting birth defects early in pregnancy.
• This allows doctors to prepare better treatments or discuss options with parents, as some birth defects can significantly affect the baby's life and health.
• There are two main stages for testing during pregnancy:
  • First-Trimester Screening (Weeks 11-14): involves blood tests checking for β-hCG (high in Down syndrome) and PAPP-A (low in babies with chromosome issues).
  • An ultrasound scan (Nuchal Translucency Test) checks fluid at the back of the baby's neck.
• Non-Invasive Prenatal Testing (NIPT) examines baby's DNA in the mother's blood.
• Second-Trimester Screening (Weeks 15-22): a quadruple blood test checks four markers: AFP (high in spina bifida, low in Down syndrome), β-hCG (high in Down syndrome, low in Edwards syndrome), and Estriol & Inhibin-A (help detect chromosome problems).
• An ultrasound (Anomaly Scan) is performed to check for physical abnormalities.
• Amniocentesis (optional) tests amniotic fluid for genetic issues but carries a small risk of miscarriage.

Birth Defects Found in Screening

• Chromosomal disorders happen due to an extra or missing chromosome.
  • Down Syndrome (Trisomy 21) affects growth, causes learning disabilities, and heart problems.
  • Edwards Syndrome (Trisomy 18) results in severe disabilities, and most babies don't survive beyond a year.
  • Patau Syndrome (Trisomy 13) causes serious brain, heart, and facial defects.
• Neural Tube Defects (NTDs) happen when the baby's spine or brain doesn't form properly.
  • Spina Bifida: baby's spinal cord is exposed, leading to mobility issues.
  • Anencephaly: baby's brain doesn't fully develop, and survival is not possible.
  • Encephalocele: part of the brain grows outside the skull.
• Neural Crest Cell Disorders affect parts of the face, heart, and nervous system.
  • Cleft Lip & Palate: the baby's mouth doesn't close properly.
  • Heart Defects: includes Tetralogy of Fallot, where the heart doesn't pump blood properly.
  • Hirschsprung Disease: the baby's intestines don't move food properly.
  • Waardenburg Syndrome: affects hearing and causes unique skin or eye coloring.

Addressing Screening Results

• If the screening test is abnormal, doctors will offer more tests like amniocentesis or chorionic villus sampling.
• Parents receive counseling to understand options.
• Some conditions can be treated early, while others may require lifelong support.

Management and Prevention

• There is no cure for chromosomal disorders, but early therapy improves life quality.
• Folic acid supplements before and during pregnancy can prevent neural tube defects.
• Genetic testing before pregnancy helps high-risk families prepare.

Importance of Screening

• Screening helps reduce risks for the baby and mother.
• Early detection gives families time to prepare for medical care.
• Support from doctors, therapists, and community groups can help families manage conditions.
• Preventing birth defects includes genetic counseling, healthy habits, and future research (gene editing).
• Understanding gametogenesis errors is crucial to detect and prevent genetic problems before birth.
• Advanced genetic testing and future research can improve fertility and reduce genetic disorders.

Explore prenatal screening methods: first-trimester blood markers, quadruple tests for Edwards syndrome, and NIPT's advantages over traditional methods. Discusses early detection of conditions like PKU and ethical considerations in balancing risk reduction with individual autonomy.