Genetics for Nurses in Obstetric Disciplines

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Genetics for Nurses in Obstetric Disciplines

• A guide to recognition and referral of congenital
  and genetic disorders
• AUTHORS
• Golder N. Wilson MD PhD,1 Vijay Tonk PhD,2
• REVIEWERS
• Shirley Karr BSN RN,3 Joanna K. Spahis BSN CNS,4
  Shirley Myers,5 RNC, MSN, FNP, and Sherry
  Letalian RN6
• 1Clinical Professor of Pediatrics, Texas Tech
  University Health Science Center at Lubbock and
  Private Practitioner, KinderGenome Genetics,
  Dallas Texas 2Professor of Pediatrics and
  Obstetrics-Gynecology Director, Cytogenetics
  Laboratory, Texas Tech University Health Science
  Center at Lubbock3Genetics Coordinator,
  Maternal-Fetal Medicine and Genetics, Texas Tech
  University Health Sciences Center at
  Amarillo4Pediatric Clinical Nurse Specialist in
  Genetics and Coordinator of the Down Syndrome
  Clinic, Department of Genetics, Childrens
  Medical Center of Dallas5Womens Health Nurse
  Practitioner, Maternal-Fetal Medicine and
  Genetics, Texas Tech University Health Sciences
  Center at Amarillo6Pediatric Clinic Coordinator,
  Department of Pediatrics, Texas Tech University
  Health Sciences Center, Lubbock
• Acknowledgement
• This presentation was designed as part of the
  GEN-ARM (Genetics Education Network for Nursing
  Assessment, Recognition, and Management) for the
  Mountain States Region Genetics Collaborative
  (MSRGCC) contact www.mostgene.org or Ms. Joyce
  Hooker at joycehooker_at_mostgene.org

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Genetic Disorders are Common
Genetic diseases affect 5-10 of children Nurses
can recognize and refer genetic disorders without
need for esoteric genetic knowledge We will now
present cases where your nursing skills and
alertness (REYDARRecognize, EYDentify, Assess,
Refer) can greatly benefit children with genetic
diseases. These cases will introduce you to
simple principles of genetics that will give you
confidence in recognizing these patients and
foster a medical home These cases and
principles are geared to the nursing genetics
primer and resources on the GENARM CD
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Think genetics when something is unusual or
extreme

• Case example 1 A term AGA newborn product of a
  pregnancy with little prenatal care has an
  enlarged and distorted head, blue-gray sclerae
  (whites of the eyes), and deformed limbs. X-rays
  show multiple fractures, and the mother blames
  this on an auto accident at 7 months gestation.
  Do you agree?

Newborn with large head and deformed bones with
fractures by x-ray
4
This unusual presentation should prompt REYDAR
for a genetic disease

• More detailed family history would be useful,
  although many genetic disorders occur as new
  changes (new mutations)
• The symptoms of blue sclerae and multiple
  fractures could be searched on the website Online
  Mendelian Inheritance in Man (go to
  http//www.ncbi.nlm.nih.gov/entrez/ or enter OMIM
  in search engine). They point to a disorder
  called osteogenesis imperfecta (166210).
• OMIM contains gt6000 diseases that can be searched
  by symptom, name, or number associated databases
  contain genetic education, medical literature
  (PubMed), and even the complete human genome
  sequence/gene map.
• Also useful is the companion database
  www.genetests.org that lists testing (when
  available) for the particular genetic disease (go
  to the clinical laboratory section and search by
  disease name

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Suspicion of genetic disease underlying this
unusual infant led to referral and genetic
counseling for this autosomal dominant
diseasemothers guilt about her accident was
assuaged and she learned she had a 50 chance
each of her future children would have OI
The family history indicated that the mother and
other relatives had mild features of osteogenesis
imperfecta or brittle bone disease (see Chapter 2)
Family history
Pedigree
6

• Note that simple recognition and assessment of
  possible genetic disease, not sophisticated
  knowledge, optimized nursing care of this family.
  
• Nurses with additional interest in genetics can
  learn to construct pedigrees, interpret
  inheritance mechanisms, and provide recurrence
  risks for the parents (genetic counseling)
• Nurses are ideally positioned to be genetic
  counselors with their hands-on contact, emphasis
  on education, and focus on prevention
• Read chapters 2-4 in the primer to acquire the
  skills for genetic counseling

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Genetic disease can be defined by abnormal genes,
tissues, or chromosomes (genetic testing)
Categories of genetic disease relate to the steps
from gene to family (genetic hierarchy)

• A family has people with unusual symptoms
• A person has abnormal form or function (disease)
• A tissue (cell to organ) has abnormal structure
  (metabolic disorders)
• A chromosome is extra or missing (chromosome
  disorders)
• Several genes (plus environment) are abnormal
  (multifactorial disorders or susceptibilities)
• A gene (DNA to RNA to protein) is abnormal
  (Mendelian disorders

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Categories of genetic or congenital disease
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• Mendelian diseases like osteogenesis imperfecta
  have distinctive family patterns
• The pattern of affected relatives is caused by
  transmission of single genes, each with a unique
  position (locus) on the chromosome.
• The paired chromosomes 1-22 and XX in females
  imply paired genes except for X and Y genes in
  the male
• Dominant or recessive diseases result when one or
  both gene partners (alleles) are abnormal.
• Abnormal alleles can be predicted (genetic risks)
  and sometimes diagnosed through their abnormal
  DNA sequence or RNA/protein expression.

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• Sickle cell anemia is recessive, requiring both
  ß-globin alleles to be abnormal (SS versus AS
  trait or AA normal).
• Sickle cell anemia can be predicted (25 risk for
  next child) and tested (abnormal S protein or
  gene)
• Other inherited anemias can be related to
  different abnormal globin alleles (C, D, E,
  thassemias).

A or S
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• OI is caused by one abnormal allele at a collagen
  gene (genotype Oo)
• Different phenotypes of OI relate to different
  collagen alleles
• The gt6000 Mendelian diseases thus relate to a
  similar number of different genes and abnormal
  alleles.
• Characterization of abnormal alleles provides DNA
  testingfew of the gt1600 characterized disease
  genes are available to the clinic.
• Simultaneous analysis of multiple genes (DNA
  chips, arrays) is not yet practical in the way
  that karyotypes define any abnormal chromosomes

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Know categories, not rare diseases

• Mendelian diseases reflect transmission of single
  genes (abnormal alleles) DNA diagnosis

• Single genes altering development cause birth
  defects and syndromes
• Single genes altering enzyme pathways cause
  inborn errors of metabolism
• Single genes altering organ function(s) produce
  extreme or earlyonset
• examples of common disease (e.g.,
  neonatal diabetes)

Multifactorial diseases reflect multiple abnormal
genes plus environment DNA/HLA markers
Many genes altering development cause isolated
birth defects like cleft palate Many genes
altering enzyme pathways cause common metabolic
diseases (e.g., adult-onset
diabetes, hyperlipidemia) Many genes altering
organ function(s) produce adult diseases (e.g.,
schizophrenia)
Chromosomal diseases imbalance multiple genes
and cause multiple birth defects Karyotype
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REYDAR of common obstetric presentations
Recognition ? Category ? Referral ? Medical home

• Case 9Padolescent female with unplanned
  pregnancy
• Case 10PDiabetic woman who is 10 weeks pregnant
  
• Case 11PA pregnant couple and cystic fibrosis
  screening
• Case 12PA pregnant couple with infertility and
  two miscarriages
• Case 13PCouple with maternal history of mental
  retardation
• (see Chapter 1)

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Case 9P. Adolescent female with unplanned
pregnancy A 16-year-old female was referred to
obstetric clinic from the emergency room after a
diagnosis of malnutrition and a positive
pregnancy test. She had been brought in by the
police for vagrancy and alcoholism, exhibiting
poor hygiene and nutrition on examination. Fetal
ultrasound revealed a fetus of about 3 months
gestation with very small head circumference,
abnormal head shape, and intrauterine growth
retardation. Her obstetric RN recognized two
likely diagnoses, and referred her to
maternal-fetal medicine for evaluation including
level II ultrasound.
REYDAR of common obstetric presentations
Recognition ? category ? referral and management
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Poor breast-feeding may signal syndromes or
congenital disorders
Case 9P (cont) The intrauterine growth
retardation and small head circumference would be
consistent with fetal alcohol syndrome. However,
the unusual head shape and severe microcephaly by
ultrasound raised the possibility that the fetus
had anencephaly (OMIM 206500, others). Had this
young female remained in pediatric care, she
could have benefited from counseling regarding
the importance of preconception/prenatal care.
Preconceptional supplementation of folic acid can
reduce the incidence of neural tube defects like
anencephaly or spina bifida by 2/3. It is likely
that this young woman had poor nutrition with low
folic acid as part of her street lifestyle and
alcoholism.. Recognition of her social history
was the key to REYDAR, not knowledge of a rare
disease.
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Case 10P. Diabetic woman who is 10 weeks pregnant

• A 25-year-old woman with juvenile diabetes
  presents to her obstetrician at approximately 10
  weeks of pregnancy. She has had several
  hospitalizations for diabetic control and states
  that her blood sugars have been high for the past
  few weeks. The obstetric nurse discusses the
  risks of hypoglycemia, respiratory distress, and
  polycythemia for infants of poorly controlled
  diabetic mothers, but does not mention another
  risk for the fetus, which is?

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• Women with poorly controlleddiabetes have a 3-5
  fold increased risk for congenital anomalies in
  their fetus that can be remembered by
  3Cscranial, cardiac, and caudal anomalies.
  Cranial defects can include anencephaly as in
  case 9P or holoprosencephaly (photo at right)
  caudal defects underdevelopment of the
  sacrum/lower limbs (caudal regression) or spina
  bifida. Anomaly patterns like the VATER
  association (192350) or Goldenhar syndrome
  (164210) also occur at higher frequency in
  infants of diabetic mothers.

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Preconception counsel

• Stringent diabetic control in later pregnancy can
  eliminate neonatal physiologic changes like
  hypoglycemia, hypocalcemia, polycythemia, and
  respiratory problems. Lowering the risks of
  diabetic pregnancy illustrates the potential
  collaboration of pediatric and obstetric nurses
  in preconception counsel.

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Case 11P A pregnant couple and cystic fibrosis
screening A 26-year-old Caucasian woman with no
chronic illnesses presents to an obstetric nurse
practitioner for her initial prenatal visit. Her
last menstrual period was three weeks ago and a
home pregnancy test was positive. She has no
prior miscarriages or infertility and her family
history is normal. Her husband is also age 26,
Caucasian, and in good health with a normal
family history. What general risks and tests
should the nurse consider for this pregnancy and
what precautions should be mentioned regarding
significance of the test results?
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• Case 11P Discussion
• The couples general risk for birth defects will
  be 2-3--that for an average pregnancy with no
  risk factors from family illness, maternal age,
  or chronic maternal disease. The nurse must
  discuss screening tests that are available,
  including those for chromosome or single gene
  disorders. Screening has classically been
  performed when an early diagnosis would make a
  difference in disease treatment or cure, but new
  genetic and reproductive monitoring technologies
  bring new options for pregnant couples.
  Ultrasound combined with fetal markers in
  maternal blood (triple test, quad screen) now
  detects 87 of fetuses with Down syndrome when
  applied in the first trimester.

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• Case 11P Discussion (cont)
• Fetal chromosome testing by chorionic villus
  sampling (8-10 weeks) and amniocentesis (15-18
  weeks) can recognize over 200 chromosome
  disorders, but risks for miscarriage and costs
  have restricted these tests to women with
  increased risk (age over 35, prior miscarriages).

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• Routine chromosome analysis (karyotype) can be
  performed on cells fromblood (white blood cells)
  obtained from individuals or fetuses (by
  fetoscopy), chorionic villus sampling (dividing
  villus cells) or amniotic fluid (amniotic
  fibroblasts). This testing requires at least 5-7
  days for results.

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• Now a rapid FISH test is available that does not
  require stimulation of cell division and gives
  results within 2-4 hours. Rapid FISH highlights
  chromosomes commonly involved in disorderse.g.,
  13 (Patau syndrome), 18 (Edwards syndrome), or 21
  (Down syndrome), showing three versus the normal
  two FISH signals in each cell nucleus (X and Y
  probes also show Turner syndrome or document sex
  in cases of ambiguous genitalia)

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• Case 11P Discussion
• The nurse should mention early ultrasound and
  quad screening as options, but point out that
  screening tests can miss abnormal fetuses or
  raise anxiety through abnormal results with
  normal fetuses. Furthermore, abnormal quad
  screens require clarification by amniocentesis,
  an invasive procedure where abnormal results give
  options for pregnancy termination rather than any
  fetal treatment. The nurse should make sure that
  the couple understands the mental disability
  associated with many chromosome disorders, the
  positive aspects of rearing children with
  disabilities, and the couples tolerance for
  ambiguous reslts or options like pregnancy
  termination.

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• Case 11P Discussion
• Complementing chromosome analysis is DNA
  technology that allows screening for common
  mutations in certain ethnic groupse. g., cystic
  fibrosis (OMIM 219700) for Caucasians,
  hemoglobinopathies (e.g., sickle cell anemia--
  OMIM 603903) for Africans or Asians, Tay-Sachs
  disease (OMIM 272800) for Jews. Cystic fibrosis
  has an incidence of about 1 in 1600 Caucasion
  infants, with a 1 in 20 chance that the average
  Caucasian parent will be a carrier. The nurse can
  inform her Caucasian patient of cystic fibrosis
  screening but also discuss the consequences of a
  positive resulttesting the husband to see if he
  too is a carrier, then considering amniocentesis
  to test fetal DNA for the 1 in 4 chance the fetus
  will have cystic fibrosis. Although DNA testing
  is highly accurate, rare cystic fibrosis
  mutations that confer mild disease and composite
  mutations (compound heterozygotes) can limit
  predictions of putative disease severity in the
  fetus. Women should also be informed that DNA
  analysis may reveal non-paternity.

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• Case 11P Discussion
• The nurse should also emphasize that DNA testing
  is not comprehensive in the sense that a routine
  chromosome study (karyotype) can find over 200
  different chromosome disorders. DNA testing must
  be directed at the disease of interest. Costs and
  volume considerations have limited DNA testing by
  commercial laboratories (Quest, LabCorp) to the
  more common conditions like cystic fibrosis or
  sickle cell anemia.. Available DNA tests and the
  laboratories performing them can be reviewed by
  accessing the website www.genetests.org, going to
  the clinical laboratories section, and entering
  the disease of interest. Until DNA chips are
  developed that screen for hundreds of diseases,
  couples should know that the 2-3 risk for birth
  defects/genetic diseases in the average pregnancy
  remains even after specific DNA testing.

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Rules from Chapter 1

• RULE 7 Pregnancy planning and preconception
  counsel are important priorities because
  recognition of pregnancy by a missed period (3-4
  weeks embryonic age) may be too late for
  preventive measures
• RULE 8 Pregnant couples should be advised of
  increasing options for gene/chromosome screening
  as well as the limitations (e.g., false
  positives/negatives) and consequences (e.g.,
  amniocentesis, elective abortion) that may ensue.
  

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Chromosome disorders

• Miscarriages (50-60), liveborn children (0.5),
  cancer tissue (many have diagnostic
  changes)--over 200 chromosomal diseases due to
  extra or missing chromosome or parts of
  chromosomes (p small or q long arms)
• Hallmarks are multiple major or minor anomalies
  (unusual appearance) with mental disability
• Most recognized by a routine karyotype, but FISH
  is required to detect submicroscopic deletions
  (e.g., DiGeorge) or the 3 of suspect children
  who have changes on subtelomere FISH after normal
  karyotypes
• Individual submicroscopic deletions are found in
  Williams (7q), hereditary retinoblastoma (13q),
  Prader-Willi (15q), Shprintzen-DiGeorge spectrum
  (22q), and 15 others.
• Consider chromosomes in any child with
  unexplained mental disability and/or multiple
  birth defects, couples with gt2 miscarriages,
  prenatal diagnosis for women over age 35
• Prenatal diagnosis of chromosome disorders can be
  performed by preimplantation diagnosis (first
  week), chorionic villus sampling (10-12 weeks),
  or amniocentesis (15-18 weeks).
• See Chapter 7 for more information

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Case 4N Sudden deterioration and unusual odor in
a newborn after 24 hours of feeding.

• Case 12P Pregnant couple with infertility and
  two miscarriages
• A couple present to an obstetric nurse early in
  pregnancy. They are each 28 years old and have
  been trying for a successful pregnancy for 4
  years. They have had two early miscarriages at 7
  and 9 weeks, neither showing abnormalities by
  gross inspection. Both are in good health without
  chronic illnesses, and neither has any family
  history of birth defects or miscarriages. What
  concerns should the nurse address?

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Inborn errors of metabolism

• Case 12P Discussion
• A history of recurrent abortion, particularly
  when coupled with infertility, should raise
  concern about chromosome aberrations. Couples
  with three or more miscarriages will have an
  approximate 3 chance to carry a chromosome
  aberration. Most likely are balanced
  translocations where two chromosomes have joined
  together and result in no extra or missing
  chromosome material. However, the joined or
  balanced chromosomes may not segregate
  appropriately during meiotic formation of
  gametes, producing a conceptus with unbalanced
  chromosomes. The chromosome imbalance may have
  severe consequences as a miscarriage or survive
  to be born as a child with mental disability and
  birth defects.

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• Case 12P Discussion
• The nurse should offer chromosome testing to
  couples with two or more miscarriages, explaining
  the implications for explaining their
  infertility/pregnancy loss or for chromosome
  aberrations in their current pregnancy.
  Additional considerations would be maternal
  causes of pregnancy loss like chronic disease or
  clotting abnormalities that can lead to
  antiphospholipid syndrome and maternal illness.
  Couples with infertility and/or multiple
  miscarriages should also be referred to
  maternal-fetal medicine or reproductive
  endocrinologists for examination of hormone
  deficiencies (e.g., premature ovarian failure),
  clotting abnormalities (e.g., certain prothrombin
  mutations detectable by DNA analysis), or
  antiphospholipid antibodies (e.g., lupus
  anticoagulant) that can cause lethal HELLP
  syndrome (Hemolysis, Elevated Liver enzymes, Low
  Platelets-- OMIM 189800) in pregnant women.

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Inborn errors of metabolism

• Over 300 disorders with overall frequency 1 in
  600.
• Nearly all are Mendelian autosomal or X-linked
  recessivethe abnormal alleles cause their
  encoded enzyme to be defective with build-up of
  chemicals before the block and deficiency of
  those after the block
• Children with inborn errors usually have a normal
  appearance with abnormal blood chemistries (low
  glucose, anion gap, high ammonia, high lactic
  acid)
• Early recognition is key before organ damage
  occurs from acidosis, seizures, or chemical
  build-up dietary treatment is often available

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. Case 13P Couple with maternal history of
mental retardation Bob and June present to a
nurse practitioner for prenatal care at an
estimated 6 weeks of pregnancy. Bob is 26, June
24, and they had a normal daughter Karen two
years ago with no pregnancy or delivery problems.
Both are healthy and of Caucasian ancestry, and
Bobs family history is normal The nurse finds
that June is an only child, but that her mother
Gail has two brothers who have mental
retardation. In addition, Gail has a sister Joan
with with two boys and a girl, and one boy Eric
has mental retardation thought due to birth
injury. Gails other sister Jill has three boys
and two girls, and her eldest son Jim has mental
retardation of unknown cause. One of Jills
daughters has also had learning problems that
caused her to drop out of high school, and she
has a preschool son Bert with speech delay. What
concerns should the nurse address?
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• Case 13P Discussion
• Besides the usual options for genetic and fetal
  screening (ultrasound, quad screen, cystic
  fibrosis screening), the nurse should recognize
  the positive family history and recommend genetic
  evaluation. The presence of several relatives
  with the same condition (mental disability)
  brings up the possibility of Mendelian disease,
  and sketching of the family pedigree (below)
  would suggest an X-linked disorder associated
  with mental retardation. Genetic evaluation would
  inform June that her mother Gail has a 50 chance
  and she a 25 chance to be a carrier for the
  X-linked disease.

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• Case 13P Discussion
• The X-linked fragile X syndrome (OMIM 300624) is
  the most common genetic cause of mental
  disability with an estimated incidence of 1 in
  2000 males. Since June is early in her pregnancy,
  a fragile X DNA test could be performed on one of
  her male relatives to confirm or exclude this
  diagnosis. It would be ideal if one of her
  affected male relatives could be evaluated by a
  clinical geneticist so that the diagnosis of
  fragile X syndrome or another of the gt20
  syndromes associated with X-linked mental
  disability could be suspected.

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• If the diagnosis of fragile X were confirmed in a
  male relative, June could have fragile X DNA
  testing to determine if she was a carrier. If her
  relatives were not available, or if their
  evaluation could not be accomplished in a time
  frame to accomplish Junes testing and options
  for prenatal diagnosis, then June could have the
  fragile X DNA test but realize that a negative
  result would not exclude other X-linked mental
  retardation syndromes. Preconception knowledge of
  fragile X syndrome in her family with recognition
  of her carrier status would have allowed Jill and
  Bob to consider other options such as surrogate
  egg donor or in vitro fertilization with
  preimplantation genetic diagnosis (PGD) and
  implantation of an unaffected embryo. Their case
  emphasizes the value of recognizing suspect
  family histories as early as possible in order to
  provide genetic counseling and reproductive
  options.

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Rules from Chapter 1

• RULE Early screening of pregnant couples for
  positive family histories (miscarriages,
  infertility, multiple affected relatives) allows
  timely evaluation of family members and
  appropriate preconception/prenatal testing.
• RULE Common conditions like mild mental
  disability often exhibit multifactorial
  determination with lower recurrence risks (2-3)
  than the more extreme and unusual Mendelian
  conditions.

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Common disorders (like mild mental or learning
disabilities often exhibit multifactorial
determination

• Case 13P Discussion
• If Jill or Bob had only one relative with mental
  disability with no obvious pedigree pattern, then
  multifactorial determination of the mental
  disability would be most likely. The odds of
  multifactorial disability would be increased if
  the affected person was mild and did not have an
  unusual appearance or biochemical abnormalities.
  Multifactorial disorders confer a 2-3 risk for
  primary relativesi.e., siblings/parents/children.
  Since Jill and Bob had normal intellect, their
  risks from one relative with mental disability
  would be less than 2-3.

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Multifactorial Disorders
Table 4.1. Multifactorial Disorders in the
United States
Ranks first for neonatal causes of death
approximate scale (100 of predisposition
due to genetic factors as for Mendelian
disorders) to (20 of predisposition due to
genetic factors)
40
Multifactorial Disorders

• Most isolated birth defects like cleft palate,
  hypospadias, heart defects, spina bifida
• Many common diseases like diabetes mellitus,
  hypertension, mental illness, mild
  mental/learning disabilities
• Multiple genes involved, giving lower
  transmission risks (about 3 for offspring of
  affected parent, sibling to affected child)
• Therapeutic goals are to manipulate environment
  (e.g., folic acid) either generally or for
  specific high-risk individuals identified by
  associated DNA markers (more diverse and
  sensitive than HLA haplotypes

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Multifactorial disorders For some (e.g.,
coronary artery disease), single genes of major
effect (e.g., those regulating cholesterol) are
good risk markers)
Recognizing at-risk children or adolescent
females provides important opportunities for
nursing education and prevention (see chapter 4)
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Review Questions

• 1-2. A 21-year-old female was referred to
  obstetric clinic from the emergency room after a
  diagnosis of malnutrition and a positive
  pregnancy test. She had been brought in by the
  police for vagrancy and alcoholism, exhibiting
  poor hygiene and nutrition on examination. She
  also was affected with cystic fibrosis, having a
  milder disease course, and a sister had a child
  with spina bifida. Fetal ultrasound revealed a
  fetus of about 3 months gestation with very small
  head circumference, abnormal head shape, and
  intrauterine growth retardation.

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• 1. The poor malnutrition and unplanned pregnancy
  caused the young woman to miss the following
  standards of care
• Amniocentesis because of higher risks for
  chromosome abnormalities and cystic fibrosis
• Triple/Quad screening with ultrasound to screen
  for fetal chromosome abnormalities
• Preconception counsel including provision of
  vitamins with folic acid
• Prosecution because of suspected alcoholism
  causing damage to the fetus
• Preimplantation genetic diagnosis of to avoid the
  high risk for fetal cystic fibrosis
• 2. Which of the following birth defects would be
  most likely to occur in this situation?
• Congenital heart defect
• Omphalocele
• Anencephaly
• Tracheo-esophageal fistula
• Anal atresia

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• Questions 3-4
• 3. A Caucasian couple in the 20s comes in for
  preconception counseling regarding their first
  pregnancy. They have had no prior miscarriages or
  infertility and their family histories are
  normal. This lack of risk factors means that
  their risk for fetal abnormalities in this
  pregnancy is approximately
• 50
• 25
• 10
• 2-3
• lt1
• 4. Which of the following genetic screening tests
  should be considered for this couple?
• Alpha-thalassemia
• Beta-thalassemia
• Tay-Sachs disease
• Sickle cell anemia
• Cystic fibrosis

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• Questions 5-6
• 5. A couple present to an obstetric nurse for
  counseling because they have had three early
  miscarriages at 6-8 weeks gestation. Both are in
  good health without chronic illnesses, and
  neither has any family history of birth defects
  or miscarriages. Which of the following is an
  important contributor to miscarriages that can be
  tested in this couple?
• Autosomal dominant disorders
• Chromosomal disorders
• Multifactorial disorders
• Mitochondrial disorders
• X-linked recessive disorders
• 6. Which of the following results is most
  plausible for this couple, along with its
  likelihood given their history?
• Trisomy, 1
• Trisomy, 10
• Translocation, 2-3
• Translocation 20-30
• Turner syndrome, 10

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Answers 1-C 2-C

• Questions 1-2.
• The importance of preconception counsel is
  recognized by the American College of Obstetrics
  and Gynecology (ACOG). Provision of folic acid
  prior to conception (the embryo will be at least
  3 weeks along when mother misses her menstrual
  period) lowers the risk of neural tube defects
  (spina bifida, anencephaly) by 2/3. Neural tube
  defects exhibit multifactorial determination (see
  Chapter 4) with increased risk (0.5-1) to
  relatives. The woman is affected with cystic
  fibrosis (219700--autosomal recessive) and would
  be a homozygote (genotype ccsee Chapter 3) but
  the father would be unlikely to be a carrier (at
  least 19/20 chance) and thus there would be no
  indication for prenatal diagnosis. A planned
  pregnancy could have included carrier screening
  for cystic fibrosis in the father.

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Answers 3D 4E

• Questions 3-4
• The risk for any type of congenital anomaly or
  genetic disease is 2-3 for the average
  pregnancy. This risk becomes 5-6 for disease
  when children are examined at age 2-3 years
  (e.g., developmental disabilities). Caucasians
  have an increased frequency of cystic fibrosis

48
Answers 5B 6C

• Questions 5-6
• Balanced translocations in a parent are a cause
  for recurrent miscarriages because unbalanced
  gametes can be produced during meiosis, causing
  extra or missing chromosomes and developmental
  abnormalities in the conceptus (see Chapter 7).
  Couples with three miscarriages have an
  approximate 2-3 chance that one of them will
  carry a balanced translocation