Mod 14


Definitions of Common Genetic Terms

  • Trisomy: A genetic condition characterized by the presence of an extra chromosome in the cells.

  • Monosomy: A genetic condition where a chromosome is missing from the pair.

  • Nuchal Tube Defects (NTD): A spectrum of disorders that includes spina bifida occulta to anencephaly, caused by multiple genetic and environmental factors, developing within the first four weeks of pregnancy.

  • Aneuploidy: A genetic condition resulting in an abnormal number of chromosomes in a cell.

  • Trisomy 18 (Edwards Syndrome): A chromosomal disorder that leads to severe intellectual disabilities, congenital heart disease, and other developmental anomalies, with a high mortality rate in affected infants.

  • Trisomy 13 (Patau Syndrome): Characterized by severe physical abnormalities and neurological deficits, with affected infants often not surviving past infancy.

  • Trisomy 21: Also known as Down syndrome, it involves an extra copy of chromosome 21 present in every cell.

  • DIA: Dimeric inhibin A, a protein secreted by the placenta.

  • uE3 (Unconjugated Estriol): A hormone produced during pregnancy by the placenta that is measured to screen for chromosomal abnormalities.

  • Maternal Multiple Marker Serum (MMS) Screening: A second-trimester test that screens for trisomy 18, trisomy 21, and NTDs.

  • Carrier Screening: A type of testing that helps couples identify if they carry genes for specific inherited conditions, especially those inherited in an autosomal recessive or X-linked manner.

Types of Genetic Disorders

  • Monogenic Disorders: Diseases caused by mutations in a single gene, examples include:

    • Cystic Fibrosis

    • Fragile X Syndrome

    • Sickle Cell Disease

    • Alpha- and Beta-Thalassemia

    • Spinal Muscular Atrophy

    • Tay-Sachs Disease

  • Normal Genetic Makeup:

    • Humans have 23 pairs (46 total) chromosomes in each cell.

    • Meiosis: The process of producing sex cells (gametes).

  • Chromosomal Abnormalities:

    • The “Missing or Extra Pages” Glitch: Pertains to large segments of DNA being missing, duplicated, or translocated.

    • Example includes Down syndrome which features an entire extra chromosome 21.

  • Single-Gene Disorders:

    • The “Typo” Glitch: Small mutations in individual genes preventing normal function.

    • Examples: Cystic Fibrosis, Sickle Cell Anemia.

  • Polygenic/Multifactorial Disorders:

    • The “Bad Luck Combo” Glitch: Result from multiple genetic factors and lifestyle together triggering the disease.

    • Examples: Heart disease, Type 2 diabetes, Obesity.

  • Teratogenic Disorders:

    • The “Outside Interference” Glitch: These are not inherited but caused by environmental factors affecting development, such as drugs or infections.

    • Examples: Fetal Alcohol Syndrome (FAS), defects from Zika virus.

Genetic Tests for Pregnancy

  1. 1st Trimester Screening for Aneuploidy:

    • Timing: 11 to 13 6/7 weeks gestation.

    • Indication & Reliability: Includes nuchal translucency (NT) measurement and maternal serum measurements of free/total β-hCG and PAPP-A. A positive result allows for earlier prenatal diagnostic options.

    • Procedure: Blood test.

    • Risks & Ethical Ramifications: Advantages include privacy and reduced health risks compared to later screening tests.

  2. Nuchal Translucency Ultrasound:

    • Indication: Screens for aneuploidy; increased NT size indicates higher risk for genetic defects.

    • Patients with positive screenings may be recommended for diagnostics like amniocentesis or CVS.

  3. 2nd Trimester Serum Screening for Aneuploidy (Triple Screen):

    • Timing: 16-18 weeks gestation.

    • Indication & Reliability: Screens for NTDs, trisomy 18, and 21 with detection rates of 69% and a 5% false positive rate.

    • Procedure: Blood test to measure AFP, hCG, and uE3.

    • Risks & Ethical Ramifications: Sensitivity for Down syndrome is lower than the first trimester; risks exist with later terminations.

  4. Quad Screen:

    • Timing: 15-22 weeks gestation.

    • Indication & Reliability: Similar to the triple screen but includes a dimeric inhibin A measurement, increasing detection to 81% with a 5% false positive rate.

  5. Penta Screen:

    • An additional MMS test that increases the detection rate for Down syndrome by 2% over the quad screen.

  6. Integrated Screening for Aneuploidy:

    • Combines first trimester NT and serum testing with second trimester quad screen, yielding the highest sensitivity and lowest false-positive rate.

    • Procedure: First tri-screening and then interpreting results via second tri-screening.

  7. Sequential Screening for Aneuploidy:

    • First trimester results inform further testing or confirmatory diagnostics, with final risk assessments made post second-trimester testing.

  8. Cell-free DNA Testing (cfDNA or non-invasive prenatal screening [NIPS]):

    • Timing: Testing can start from 9-10 weeks gestation.

    • Reliability: High specificity and sensitivity for Down syndrome (≥99%) but doesn’t assess NTD risks. Contrast with serum AFP tests recommended alongside.

    • Procedure: Blood test assessing cfDNA from the placenta.

  9. Ultrasound (Fetal Anomaly Scan):

    • Typically conducted between 16-20 weeks of gestation for diagnosing structural defects and assessing risks in flagged cases.

    • Risks & Ethical Ramifications: Must ensure informed consent and educate the expecting parent on the potential implications of the ultrasound.

Diagnostic Testing

  1. Chorionic Villus Sampling (CVS):

    • Timing: 10-12 weeks for most, can be conducted between 10-14 weeks asynchronously.

    • Indication: Diagnostic for AMA, abnormal first-trimester screens, and genetic disorders.

    • Procedure: This test involves retrieving placental tissue for analysis.

    • Risks: Includes potential miscarriage and complications if performed too early.

  2. Amniocentesis:

    • Timing: Typically performed between 15-20 weeks, when membranes are fused.

    • Indication: Diagnostic for genetic conditions, measuring AFP for NTD screening.

    • Procedure: Involves ultrasound-guided needle extraction of amniotic fluid.

    • Risks: Low rates of complications; however, they exist.

  3. Percutaneous Umbilical Blood Sampling (PUBS):

    • Timing: Performed from 18 weeks onwards.

    • Indication: Serves as a diagnostic test monitoring fetal blood conditions.

    • Risks: Includes serious procedure-related risks.

Carrier Screening Tests

  • Diseases Targeted: SMA, Cystic fibrosis, hemoglobinopathies, Fragile X, Tay Sachs.

  • Procedure: Blood test or buccal swabs offered to both parents.

Down Syndrome (Trisomy 21)

  • Etiology: Most common trisomy leading to chromosomal abnormalities; additional chromosome results in Trisomy 21.

  • Risk Factors: Increased maternal age and related health risks.

  • Features: Variable intellectual disability, distinct facial features, congenital heart defects, gastrointestinal anomalies, and vision/hearing problems.

Screening Tests for Specific Conditions

  1. Tay Sachs Screening:

    • Characteristics: Disease affects the brain leading to progressive decline with no treatment.

    • Carrier frequency: Ashkenazi Jewish 1/30; French Canadian 1/15 to 1/30.

  2. Cystic Fibrosis Screening:

    • Characteristics: Causes thick mucus in lungs and GI tract, treated symptomatically.

    • Carrier Frequency: European/White 1/29.

  3. Spinal Muscular Atrophy Screening:

    • Characteristics: Severe muscle weakness with a high mortality rate in childhood.

    • Carrier Frequency: European/White 1/47.

  4. Fragile X Screening:

    • Characteristics: X-linked condition leading to developmental disorders.

    • Carrier Frequency: XX chromosomes 1/151; XY chromosomes 1/468.

  5. Sickle Cell Anemia Screening:

    • Characteristics: Blood disorder with various symptoms and potential complications.

    • Carrier Frequency: African ancestry 1/8 to 1/10.

  6. Thalassemia Screening:

    • Characteristics: Can range from mild to severe anemia with potential pregnancy complications.

    • Carrier Frequency: Southeast Asian 1/4 to 1/60; African American 1/15 to 1/50.

  7. Familial Dysautonomia:

    • Characteristics: Affects the nervous system leading to significant health complications.

    • Carrier Frequency: Ashkenazi Jewish 1/27.

  8. Canavan Disease:

    • Characteristics: Results in severe brain damage with early mortality.

    • Carrier Frequency: Ashkenazi Jewish 1/55; general population 1/300.

Ethical Considerations in Genetic Counseling

  • Emphasizes the need for thorough informed consent regarding genetic testing and understanding genetic histories.

  • Highlights the critical role of midwives, WHNPs, and genetic counselors in guiding patients through genetic tests and potential implications.

  • Recognizes the social impact of bias, racism, and discrimination on screening processes and healthcare outcomes for genetic diseases.