Transcript Genetics for Nurses in Obstetric Disciplines A guide to recognition and referral of congenital and genetic disorders AUTHORS: Golder N.

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 Lubbock; 3Genetics Coordinator, Maternal-Fetal Medicine and
Genetics, Texas Tech University Health Sciences Center at Amarillo;4Pediatric Clinical Nurse Specialist in Genetics and
Coordinator of the Down Syndrome Clinic, Department of Genetics, Children’s Medical Center of Dallas5Women’s Health
Nurse Practitioner, Maternal-Fetal Medicine and Genetics, Texas Tech University Health Sciences Center at
Amarillo;6Pediatric 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 [email protected]
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 (REYDAR=Recognize, 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
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
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 >6000 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
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
Suspicion of genetic disease underlying this unusual infant led to
referral and genetic counseling for this autosomal dominant disease—
mother’s guilt about her accident was assuaged and she learned she
had a 50% chance each of her future children would have OI
• 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
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
Genetic disease can be defined by abnormal
genes, tissues, or chromosomes (genetic testing)
Categories of genetic or congenital disease
Disease category1
Number of
diseases
Aggregate
frequency2
Shortened
lifespan
Major
handicap
(%)
Mendelian
> 4500
1
++3
+++
Chromosomal
> 100
0.5
++++
++++
Multifactorial
> 100
5-10
++
+++
Metabolic errors
> 500
0.3
+++
++++
Syndromes
> 1000
0.7
+++
++++
Isolated anomalies
> 200
2-3
+
++
Total
> 5000
10-12
++
+++
• 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.
Sickle cell anemia is
recessive, requiring
both β-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
• OI is caused by one abnormal
allele at a collagen gene
(genotype Oo)
• Different phenotypes of OI
relate to different collagen
alleles
• The >6000 Mendelian
diseases thus relate to a
similar number of different
genes and abnormal alleles.
• Characterization of abnormal
alleles provides DNA testing—
few of the >1600 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
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 early–onset
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
REYDAR of common obstetric presentations
Recognition → Category → Referral ↔ Medical home
• Case 9P—adolescent female with unplanned
pregnancy
• Case 10P—Diabetic woman who is 10 weeks
pregnant
• Case 11P—A pregnant couple and cystic fibrosis
screening
• Case 12P—A pregnant couple with infertility and
two miscarriages
• Case 13P—Couple with maternal history of
mental retardation
(see Chapter 1)
REYDAR of common obstetric presentations
Recognition  category  referral and management
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.
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.
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?
Women with poorly controlleddiabetes
have a 3-5 fold increased risk for
congenital anomalies in their fetus
that can be remembered by 3Cs—
cranial, 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.
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.
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?
• Case 11P: Discussion
• The couple’s 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.
• 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).
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.
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 disorders—e.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)
Cloned DNA segment
from target chromosome
13
18
21
X
Y
FISH probes
Fluorescent label
13, X, Y
No culture or need for
metaphase spreads
18
21
Male with
trisomy 13
• 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 couple’s
tolerance for ambiguous reslts or options like
pregnancy termination.
Case 11P: Discussion
Complementing chromosome analysis is DNA technology that allows
screening for common mutations in certain ethnic groups—e. 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 result—testing 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.
• 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 23% risk for birth defects/genetic diseases in the average
pregnancy remains even after specific DNA testing.
Rules from Chapter 1
• RULE 7: Pregnancy planning and preconception
counsel are important priorities because
recognition of pregnancy by a missed period (34 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.
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 >2 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
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?
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.
• 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.
Inborn errors of metabolism
• Over 300 disorders with overall frequency 1 in 600.
• Nearly all are Mendelian autosomal or X-linked
recessive—the 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
.
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 Bob’s 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. Gail’s other sister Jill has three boys and two
girls, and her eldest son Jim has mental retardation of unknown cause. One
of Jill’s 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?
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.
Gail
Joan
Jill
June
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
>20 syndromes associated with X-linked mental
disability could be suspected.
• 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 June’s
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.
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.
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 23% risk for primary relatives—i.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%.
Multifactorial Disorders
Table 4.1. Multifactorial Disorders in the United States
Disorder or
category
Cause of
death
Prevalence
Numbers
affected
(rank)
(%
population)
(millions)
Hereditability
[Genetic risk factors]
(high ++++ to low +)
Heart disease
1
3
7
++ [Cholesterol uptake]
Cancer
2
5
6
++ [Oncogenes]
Stroke
3
<1
0.6
+ [Cholesterol, blood
clotting]
Accidents
4
<1
3
+
Diabetes
mellitus
7-8
4
11
++ [Insulin secretion,
action]
Suicide
8-9
<1
0.1
++ [Schizophrenia,
alcoholism]
Congenital
anomalies*
9-10
5
3
++ [Developmental genes]
[Alcohol and drug use]
*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)
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
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)
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.
•
A.
B.
C.
D.
E.
•
A.
B.
C.
D.
E.
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
•
•
A.
B.
C.
D.
E.
•
A.
B.
C.
D.
E.
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%
<1%
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
•
•
A.
B.
C.
D.
E.
•
A.
B.
C.
D.
E.
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%
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 cc—see 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.
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 56% for disease when children are
examined at age 2-3 years (e.g.,
developmental disabilities). Caucasians
have an increased frequency of cystic
fibrosis
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