Genetics in Reproduction Maternal/Fetal Diagnostics NUR 264

Genetics

Reproduction 46 chromosomes – 22 + sex (XY)

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

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

Monosomy Missing a chromosome – 45 Incompatible w/ life

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

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

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

Deletion Cri du chat Syndrome 99% abort

Translocation Transfer of part or entire chromosome Chronic Myelogenous Leukemia

Sex Chromosome - Monosomy Turner Syndrome– one X chromosome

Sex Chromosome - Trisomy Klinefelter Syndrome– XXY chromosomes

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

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

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

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

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

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

X-Linked Recessive Inheritance

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

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

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

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

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

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.

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

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

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

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

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.

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

Newborn Screening

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

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

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

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

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

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

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

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

Fetal Surgery Spina bifida surgery

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

Cloning

Parthenogenesis

Stem Cells

Umbilical Cord Blood

Human Genetic Engineering

Pre-implantation Genetic Engineering

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

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

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

FIGURE 6–13 X-linked recessive pedigree. The mother is the carrier 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.

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.