1. Genetics in Reproduction Maternal/Fetal Diagnostics
NUR 264

2. Genetics

3. Reproduction
46 chromosomes – 22 + sex (XY)

4. Risk Factors Miscarriage Familial Age
Genetic defects cause 60% spontaneous abortions
Familial
Incidence ↑s w/ subsequent pregnancies
Type 2 diabetes, neural tube defects, metabolic disorders
Age
>35 years of age
Adolescent – hormone, diet, smoking, drugs

5. Risk Factors Nutrition Environment Multifactorial
Malnutrition, folic acid deficiency
↓ Protein → congenital heart disease
Iron deficiency anemia → SGA
Environment
Teratogens – drugs (phenytoin, warfarin), alcohol, smoking (O2 deprivation, HTN → CP), radiation, infection (Rubella, CMV)
Multifactorial
5 – 10% cancers have genetic markers

6. Monosomy
Missing a chromosome – 45
Incompatible w/ life

7. Trisomy Down’s Syndrome – extra chromosome
↑ incidence w/ ↑ parental age

8. Mosaicism
Two different genetic materials in same person – different chromosome numbers
Mixture of normal 46 chromosome cells and abnormal 47 chromosome cells
More common in sex chromosomes
Down’s syndrome w/ near normal intelligence

9. Breakage Loss or gain of a chromosome Causes:
Chemicals (smoking, drugs), radiation, viruses
Linked to leukemia, colon cancer

10. Deletion
Cri du chat Syndrome
99% abort

11. Translocation Transfer of part or entire chromosome
Chronic Myelogenous Leukemia

12. Sex Chromosome - Monosomy
Turner Syndrome– one X chromosome

13. Sex Chromosome - Trisomy
Klinefelter Syndrome– XXY chromosomes

14. Modes of Inheritance Mendelian Nonmedelian Homozygous Heterozygous
Single-gene inheritance
Nonmedelian
Multifactorial inheritance
Homozygous
Two identical genes
Heterozygous
Two forms of same gene
Every pregnancy has 3% - 4% risk for infant w/ birth defect

15. Autosomal Dominant Disorders
Affected Person
Has an affected parent
One child may have more severe form of disorder
50% chance of having an affected child with each pregnancy
No carriers
Males and females are equally affected
Father can pass abnormal gene onto son

16. Autosomal Dominant Disorders
Common disorders
Huntington disease
Degeneration of brain – C #4
Polycystic kidney disease
Neurofibromatosis (von Recklinghausen disease)
Achondroplastic dwarfism

17. Autosomal Recessive Disorders
Both parents must be carrier or have trait
Males and females are affected
Each offspring has 25% chance of having disease
50% chance of being carrier
Common disorders
Cystic fibrosis
Sickle-cell anemia – C #9
Tay-Sachs disease
Most metabolic disorders (PKU)
Albinism

19. X-Linked Recessive Disorders
No male-to-male transmission
50% chance carrier mother passes abnormal gene to son who is affected
50% chance daughter of a carrier mother will be a carrier
100% chance that daughter of affected father will be a carrier
Affected daughter must have affected father and affected or carrier mother

20. X-linked Recessive Inheritance
Hemophilia:
Female carrier
Male w/ disease

22. X-Linked Recessive Inheritance

23. X-Linked Recessive Disorders
Common disorders
Hemophilia
Duchenne muscular dystrophy
Color blindness

24. X-linked Dominant Disorders
Abnormal gene or break on the X chromosome
No male-to-male transmission
Affected fathers will have affected daughters, due to passage of X chromosome
Heterozygous mother has 50% chance passing abnormal gene to children
Disorder: Vitamin D-resistant rickets
Fragile X Syndrome

25. Multifactorial Disorders
Combination of causative factors
Genetic & environmental factors
Mild to severe malformations
Sex-biased
Males – pyloric stenosis, Females – cleft palate
Risk ↑s w/ more family members affected
Disorders:
Cleft lip & cleft palate, clubfoot, spina bifida
Hypertension, diabetes, heart disease, mental illness

26. Multifactorial Disorders
Cleft lip and cleft palate
Spina bifida w/ Ultrasound

27. Prenatal Diagnostic Tests
Genetic ultrasound
To assess the fetus for genetic or congenital problems – best done at 16 to 20 weeks
Genetic amniocentesis
Helps in the identification of genetic disorders
Chorionic villus sampling
Diagnostic information available at 8 to 12 weeks’ gestation
Products of conception tested directly

28. B, Chorionic villus sampling is done at 8 to 12 weeks,
A, Genetic amniocentesis for prenatal diagnosis is done at 16 to 20 weeks’ gestation.
B, Chorionic villus sampling is done at 8 to 12 weeks,
and the cells are karyotyped within 48 to 72 hours.

29. Prenatal Diagnostic Tests
Percutaneous umbilical blood sampling
To obtain fetal blood – 2nd & 3rd trimesters
Facilitates rapid chromosome diagnosis and genetic studies
Alpha-Fetoprotein
Done at l5 to 22 weeks’ gestation
High levels associated with open neural tube defects, gastroschisis, multiples
Low levels associated with Down syndrome
If abnormal, perform U/S & amniocentesis

30. Prenatal Diagnostic Tests
Quad Marker Screen
Alpha-fetoprotein, Unconjugated estriol, hCG, Inhibin-A (placental hormone)
Performed at 10 to 20 weeks
High hCG and Inhibin-A = Down syndrome
Low UE = Down syndrome
Triple Screen
AFP, UE, hCG
Quad Screen with FASTER and PAPPA
Nuchal thickness, preg.-assoc. plasma protein A
Performed second trimester for Down syndrome

31. Prenatal Diagnostic Tests
Fetal tissue sampling
Performed through fetoscope at 18 weeks
Disorders:
Metabolic disorders, coagulation disorders, immunodeficient disorder
Chromosome abnormalities
Skin defects
Cultural background recommendations

32. Postnatal Diagnostic Tests
Complete and detailed history
Determines whether the problem is prenatal
Assists in identifying if the problem is postnatal
Helps to determine familial origin
Physical examination
Dermatoglyphics analysis

33. A
Dermatoglyphic patterns of the hands in A, a normal individual, and B, a child with Down syndrome. Note the single transverse palmar crease, distally placed axial triradius, and increased number of ulnar loops.

34. Postnatal Diagnostic Tests
Laboratory analysis
Chromosome analysis
Enzyme assay
inborn errors of metabolism
Antibody titers
infectious teratogens
DNA studies

35. Newborn Screening

36. Indications for Testing
Advanced maternal age - age 35 or older
Family history
Chromosomal or metabolic disorder
Birth defects
Mental retardation
Parent with balanced translocation (chromosomal abnormality) - risk that approximately 10% to 15% children will be affected
If the father is the carrier, 2% to 5% risk

37. Indications for Testing
Previous child with chromosomal disorder - 1% to 2% risk of future child having chromosomal abnormality
Mother carrying an X-linked disease - risk of affected male fetus is 50%
Ethnic group with history of chromosomal disorders
Parents carrying an inborn error of metabolism - may be diagnosed in utero

38. Indications for Testing
Couples with a history of two or more first trimester spontaneous abortions
Both parents carrying an autosomal recessive disease - sickle cell disease
Women with an abnormal serum alpha-fetoprotein test

39. Emotional Impact Concern for infant’s survival Anger
Grief - loss of perfect baby
Guilt
Strife within the family
Possibility of lifelong difficulties
Fear of results of testing
Blame for infant’s disorder

40. The Nurse’s Role Supports the family decisions
Helps families to acquire adequate information
Clarify issues for the family
Helps them understand information
Educate family
Nutrition, health care
Family planning, parenting skills

41. The Nurse’s Role (cont’d)
Acts as a liaison between family and genetic counselor
Provides information about support groups
Provides continuity of care to the family
Provides follow-up care
Uses appropriate referral systems
Early screening & developmental programs

42. Legal & Ethical Issues Family planning Abortion – therapeutic
Fetal surgery
Reproductive assistance
Cloning
Parthenogenesis
Stem cells
Umbilical Cord Blood
Human Genetic Engineering

43. Fetal Surgery Experimental
Open uterus in second trimester, treat lesion, replace fetus in uterus
Risk
Premature labor, uterine rupture, hemorrhage
Cesarean section deliveries only
Disorders:
Neural tube defects, gastroschisis

44. Fetal Surgery
Spina bifida surgery

45. Reproductive Assistance
Therapeutic insemination
Depositing sperm in to woman
In vitro fertilization, embryo transfer
Deposit fertilized egg & sperm in to woman
25% success rate
Surrogate childbearing
Insemination w/ sperm or egg and sperm

46. Cloning

47. Parthenogenesis

48. Stem Cells

50. Umbilical Cord Blood

51. Human Genetic Engineering

52. Pre-implantation Genetic Engineering

54. Implications for Nurses
Learn to anticipate ethical dilemmas
Clarify your own values re: issues
Understand legal implications
Develop appropriate strategies for ethical decision-making
Read about bioethical issues
Attend workshops

57. Autosomal dominant pedigree. One parent is affected
Autosomal dominant pedigree. One parent is affected. Statistically, 50% of offspring will be affected, regardless of sex.

58. FIGURE 6–12 Autosomal recessive pedigree. Both parents are carriers
FIGURE 6– Autosomal recessive pedigree. Both parents are carriers. Statistically, 25% of offspring are affected, regardless of sex.

59. FIGURE 6–13 X-linked recessive pedigree. The mother is the carrier
FIGURE 6– X-linked recessive pedigree. The mother is the carrier. Statistically, 50% of male offspring are affected, and 50% of female offspring are carriers.

60. Screening pedigree. Arrow indicates the nearest family member affected with the disorder being investigated. Basic data have been recorded. Numbers refer to the ages of the family members.