Download Genetics in Reproduction

Genetics in Reproduction
Maternal/Fetal Diagnostics
NUR 264
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Genetics
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Reproduction
• 46 chromosomes – 22 + sex (XY)
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Risk Factors
• Miscarriage
– 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
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Risk Factors
• Nutrition
– 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
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Monosomy
• Missing a chromosome – 45
• Incompatible w/ life
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Trisomy
• Down’s Syndrome – extra chromosome
• ↑ incidence w/ ↑ parental age
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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
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Breakage
• Loss or gain of a chromosome
• Causes:
– Chemicals (smoking, drugs), radiation,
viruses
• Linked to leukemia, colon cancer
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Deletion
• Cri du chat Syndrome
• 99% abort
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Translocation
• Transfer of part or entire chromosome
• Chronic Myelogenous Leukemia
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Sex Chromosome - Monosomy
• Turner Syndrome– one X chromosome
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Sex Chromosome - Trisomy
• Klinefelter Syndrome– XXY chromosomes
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Modes of Inheritance
• Mendelian
– 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
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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
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Autosomal Dominant Disorders
• Common disorders
– Huntington disease
• Degeneration of brain – C #4
– Polycystic kidney disease
– Neurofibromatosis (von Recklinghausen
disease)
– Achondroplastic dwarfism
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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
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Cystic fibrosis
Sickle-cell anemia – C #9
Tay-Sachs disease
Most metabolic disorders (PKU)
Albinism
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X-Linked Recessive Disorders
• X-Linked recessive
– 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
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X-linked Recessive Inheritance
• Hemophilia:
• Female carrier
• Male w/ disease
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X-Linked Recessive Inheritance
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X-Linked Recessive Disorders
• Common disorders
– Hemophilia
– Duchenne muscular dystrophy
– Color blindness
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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
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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
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Multifactorial Disorders
• Cleft lip and cleft palate
• Spina bifida w/ Ultrasound
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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
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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.
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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
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Prenatal Diagnostic Tests
• Quad Marker Screen
– Alpha-fetoprotein, Unconjugated estriol, hCG, InhibinA (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
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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
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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
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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.
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Postnatal Diagnostic Tests
• Laboratory analysis
– Chromosome analysis
– Enzyme assay
• inborn errors of metabolism
– Antibody titers
• infectious teratogens
– DNA studies
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Newborn Screening
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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
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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
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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 alphafetoprotein test
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Emotional Impact
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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
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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
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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
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Legal & Ethical Issues
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Family planning
Abortion – therapeutic
Fetal surgery
Reproductive assistance
Cloning
Parthenogenesis
Stem cells
Umbilical Cord Blood
Human Genetic Engineering
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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
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Fetal Surgery
• Spina bifida surgery
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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
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Cloning
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Parthenogenesis
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Stem Cells
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Umbilical Cord Blood
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Human Genetic Engineering
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Pre-implantation Genetic
Engineering
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Implications for Nurses
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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
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Autosomal dominant pedigree. One parent is affected. Statistically, 50% of offspring will be
affected, regardless of sex.
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FIGURE 6–12
Autosomal recessive pedigree. Both parents are carriers. Statistically, 25%
of offspring are affected, regardless of sex.
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FIGURE 6–13
X-linked recessive pedigree. The mother is the carrier. Statistically, 50% of
male offspring are affected, and 50% of female offspring are carriers.
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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.
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