Genetics for Maternal Child
Health Nursing
Brandy M. Freschi (Smolnik), MS, CGC
Certified Genetic Counselor
Perinatal Associates of Northern Nevada
www.renoperinatal.com
Ph 775-829-0573 Fax 775-329-8528
Overview
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Genetic Counselors & Genetic Counseling
Prenatal Genetics
Neonatal & Pediatric Genetics
Pregnancy Loss
Grief/Bereavement
Genetic Counselors
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Genetic counselors are health professionals with specialized Master’s degrees and experience in the areas of medical
genetics and counseling.
– Accredited by the American Board of Genetic Counseling; require specific competencies, case load/type, and
coursework
– Board certification required; Licensure available in only some states
Genetic counselors work as members of a health care team, who provide information and support to families who
have members with or are at risk for birth defects and/or genetic/inherited disorders by:
– Identify families at risk
– Investigate the problem present in the family
– Interpret information about the disorder
– Analyze inheritance patterns and risks of recurrence
– Review available testing and treatment options with the family
Genetic counselors also:
– Provide supportive counseling to families
– Serve as patient advocates
– Refer individuals and families to community or state support services.
– They serve as educators and resource people for other health care professionals and for the general public
Settings:
– Prenatal, Pediatric/Adult, Cancer, Laboratory, Research, Specialty Disease Clinics, etc.
Non-directiveness
– Unique from other disciplines/settings in health care
– Important because genetics often involves reproductive decisions which are made involving many factors:
• Magnitude of risk
• Burden of impact of disorder
• Individual perception of impact
• Meaning of children
• Individual cultural, religious or personal preferences
Why is Genetics Important in
Maternal Child Health Nursing?
• Incidence of chromosome abnormalities 1/200
• 40-60% of admissions to children hospitals are
for genetic or genetic related conditions
• Thousands of genetic conditions exist with
new ones discovered regularly
• Majority of all deaths have a genetic
component
Prenatal Genetics
Indications for a Genetic
Counseling Referral
FINDING
• Increased risk for
aneuploidy
– AMA (35-singleton; 33twins)
– Positive serum screen
– Abnormal ultrasound
marker/finding
– Family history
chromosome
abnormality
REASON TO CONSIDER
CONSULTATION
• Discuss risks to pregnancy
and available testing
options
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CVS
Amniocentesis
1st or 2nd tri screening
Level II ultrasound
Aneuploidy
• Definition:
– The occurrence of one or more extra or missing
chromosomes leading to an unbalanced chromosome
complement, or, any chromosome number that is not an
exact multiple of the haploid number
• Most common type of chromosome abnormality
• Examples:
– Trisomy: one extra chromosome for a total of 47
– Monosomy: one missing chromosome for a total of 45
• Typically not inherited, most trisomies occur due to
nondisjunction
Case #1
• 37 y, G4P3
• Referred for advanced maternal age (AMA)
and first trimester screening
• Ultrasound at initial visit revealed fetus had
increased nuchal translucency (3.6 mm)
• Pt declined FTS and CVS; elected to proceed
with amniocentesis after 16 weeks
• Results were consistent with trisomy 21
(Down syndrome)
Case #1
Trisomy 21: Down syndrome
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Most common aneuploidy, 1/800
births
Mental retardation:
– Typically mild to moderate but
encompasses full range of
ability-disability
Characteristic facial features
Hypotonia
Feeding and breathing difficulties
Congenital heart defects:
– 50% of all affected individuals
– Typically AV canal defects
Trisomy 21 is not inherited, due to
nondisjunction which is a risk for
each and every pregnancy at any
maternal age
Average life span 50-60
http://bagnewsnotes.typepad.com/bagnews/images/Trig1.jpg
Nuchal translucency
Normal translucency
Increased nuchal translucency
Down syndrome (Trisomy 21)
http://images1.clinicaltools.com/images/
gene/karyotypes/trisomy21.jpg
Case #2
• 34 y o, G1P0
• Referred due to abnormal ultrasound findings:
choroid plexus cysts, clenched hands, and possible
heart defect
• Findings above were confirmed also IUGR was noted
• Patient was counseled on increase risk for
chromosome aneuploidy
• Amniocentesis performed and karyotype revealed
trisomy 18 (Edwards syndrome)
Case #2
Trisomy 18: Edwards Syndrome
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1/3000 births
IUGR
Brain abnormalities
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CPCs
Heart defects
Renal abnormalities
Dysmorphic features:
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Hypotonia
Seizures
Short palpebral fissures
Micrognathia
Low set ears
Clenched fists
Cleft lip/palate
Rocker-bottom feet
Hearing loss
Feeding and breathing difficulties
High mortality rate: 90% are
miscarried or stillborn; 90% die
within first year of life (most within
the first few days)
http://www.ninetynineballoons.com/
Trisomy 18
Case #3
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27 y o, G4P2
Referred for first trimester screening
Ultrasound revealed a cystic hygroma
Pt declined screening and opted for CVS
Results were 45,X or Turner syndrome
http://www.turnersyndrome.org
Case #3
45, X: Turner syndrome
• 1/2,500 births
• Heart defects
– Coarctation of the aorta
• Short, webbed neck
• Low set ears
• Swollen hands and feet
• Not associated with MR but may
specific learning issues (math, etc)
• Short stature
• Early loss of ovarian function
• Very high miscarriage rate but if
liveborn has a very good
outlook/prognosis
Case #3 Ultrasound Pictures
Turner syndrome (45,X)
https://images1.clinicaltools.com/images/
gene/karyotypes/turnersyndromexnoy.jpg
Prenatal Testing for
Aneuploidy
• In 2007, the American College of Obstetrics
and Gynecology recommend that ALL women
regardless of age should be counseled the risk
of having a pregnancy with aneuploidy and
given the option of both prenatal screening and
prenatal diagnosis testing options
Modes of Prenatal Screening
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Principles of Prenatal Screening:
– Uses various noninvasive tools (maternal serum, ultrasound) to provide a risk assessment for
the most common trisomies
– It is not able to diagnose these conditions but determines if the patient is at either an increased
or normal risk
• False positives and false negatives, cannot detect other conditions
Types
– First trimester screen
• 11-14 weeks gestation
• Combines maternal age, ultrasound nuchal translucency measurements, evaluation of the
nasal bone, and maternal serum levels of PAPP-A and free beta hCG
• Provides an adjusted risk for trisomy 21, 18, and 13 (x:xxx chance)
• Up to 91-95% detection for trisomy 21; 95% for trisomy 18 & 13
• Does not screen for ONTDs; f/u with serum AFP only and/or u/s in 2nd tri
– Second trimester screen (multiple marker; AFP quad, AFP tetra)
• 15-20 weeks gestation
• Combines maternal age with serum levels of AFP, hCG, unconjugated estriol, and inhibin
A
• Provides an adjusted risk for trisomy 21, 18, and open neural tube defects (x:xxx chance)
• 75-80% detection for trisomy 21; 60% for trisomy 18, and 80-85% for ONTDs
– Integrated or Sequential Screening
• Combines first & second trimester screening for ~90% detection of DS, 80% for T18
Modes of Prenatal Screening
– Non-Invasive Prenatal Diagnosis
• Became available in the last year, still under study
• Maternal serum screening starting at 10 weeks which evaluating cell-free
fetal DNA that circulates in maternal blood and determines the
concentration of specifically tagged chromosomes
• On average, can detect:
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>99% (96-100%) detection of T21 (Down syndrome)
97%-99% (85-100%) of T18 cases
78.6%-91.7% (50-99.9%) of T13 cases
Most labs with a <1% false positive rate
• Some labs are now including analysis for Turner syndrome & the presence
of the Y chromosome
• False positives and negatives are still possible, still requires follow up
prenatal dx with CVS or amnio
– Ultrasound at 18-20 weeks
• Examines for markers/signs of chromosome aneuploidy; ONTDs, and
other isolated birth defects
• Can be somewhat center-dependent
• ~50-60% detection for trisomy 21; >90% for trisomy 18, 13 and ONTDS
• Anatomy scan by OB; detailed/level II by perinate
Modes of Prenatal Diagnosis
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Chorionic villus sampling (CVS)
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10-12 weeks gestation
Chromosome/genetic/DNA analysis
performed on a sample of the chorionic
villi
99.9% accuracy/detection of chromosome
problems (genetic/DNA testing
accuracy/detection is condition-specific)
Risk of miscarriage 1/200
No analysis of AFP for ONTDs
Performed transabdominally or
transcervically
Amniocentesis
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15-20 weeks gestation
Chromosome/genetic/DNA analysis
performed on a sample on the fetal cells
found in amniotic fluid
99.9% accuracy/detection of chromosome
problems (genetic/DNA testing
accuracy/detection is condition-specific)
Risk of miscarriage is as low as 1/1200 or
0.08%
Provides 98-99% detection for ONTDs
using analysis of amniotic fluid AFP
Tests ordered from
CVS/Amnio
• Karyotype
– Gold standard
– Karyotype is used to
identify and evaluate the
size, shape, and number
of chromosomes in the
fetus
– “Photograph” of the
chromosomes
– Detects 99.9% of all
major structural defects
(trisomies,
translocations, deletions)
Tests ordered from
CVS/Amnio
• FISH (Fluorescent in situ
hybridization)
– Probes are made to “attach” to
a specific region/section of a
chromosome
– Many utilizations:
• Probes for common aneuploidy
(allows for rapid detection)
• Probes for specific
microdeletions/microduplicatons
not able to be seen on karyotype
Tests ordered from
CVS/Amnio
• Chromosomal Microarray
– Evaluates specific areas
(typically 100s of regions)
along the human genome for
gains or losses of
chromosome segments at a
much higher resolution than
traditional karyotyping
– Typically done in cases of
abnormal ultrasound findings
and/or known family history
of microarray abnormalities
Indications for a Genetic
Counseling Referral
FINDING
• Family history genetic
disease/birth defect/mental
retardation
AND/OR
• Consanguinity
REASON TO CONSIDER
CONSULTATION
• Review pedigree, assess
degree of relatedness,
discuss recurrence risks,
methods of risk
reductions, and discuss
available testing options
The Family History in
Genetics
• Fundamental component of genetic consultation
• Visual record of the family
– Clarifying relationships between individual
– Allows for sorting of phenotypic features relevant to
condition in question
– Assists in determining the mode of inheritance if evident
• Important in establishing rapport-can learn a lot of
nongenetic information from pedigree
– Chief support people, social relationships, family “myths”
Putting it all together
Single Gene Inheritance
Autosomal Dominant
• Examples:
– Huntington Disease
– Achondroplasia
– Neurofibromatosis type 1
– Marfan syndrome
• Some cases in the family will be “de
novo” with no previous family hx
– Certain diseases are known to
have high de novo rates and
there is an increased risk with
h paternal age
Single Gene Inheritance
Autosomal Recessive
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Cystic Fibrosis
Sickle Cell Disease
Thalassemia
PKU
Galactosemia
Increased risk with
consanguinity
Single Gene Inheritance
X-Linked
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Hemophilia A & B
Duchenne MD
Colorblindness
Fragile X syndrome
Multifactorial Conditions
• Examples:
– Heart defects
• Maternal diabetes, ace
inhibitors, lithium
– Cleft lip/Cleft palate
• Cigarette smoking, folic
acid deficiency, maternal
medications
– Open neural tube defects
• Folic acid deficiency,
MTHFR, maternal
diabetes, anti-seizure
medications
Indications for a Genetic
Counseling Referral
FINDING
• Preconception/prenatal genetic
carrier testing
• Environmental Hazards
– Maternal viral infection,
teratogenic exposures
• Maternal conditions putting the
fetus at risk
– Diabetes, PKU
• Infertility/Recurrent pregnancy
loss
– Translocations; hereditary
thrombophilias; patient has
genetic/chromosomal condition
REASON TO CONSIDER
CONSULTATION
• Discuss inheritance & testing
• Discuss risks to pregnancy &
testing
• Discuss risks to pregnancy &
testing
• Discuss various etiologies &
offer workup as necessary
Carrier Screening
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Screening the population, or particular parts of the population for their risk to have
a child with a recessive disorder
Traditionally, carrier screening was performed/offered specific to the person’s
ethnicity
– Since they are recessive conditions, a normal family history does not reduce the
chances from general population risks
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1/25 Europeans are carriers of CF
1/40 Europeans are carriers of SMA
1/12 Africans are carriers of Sickle cell and other hemoglobinopathies
1/9 Ashkenazi Jews are carriers of one of 9 “Jewish” conditions
Now, with better and less expensive technology coupled with the fact that people
are more often from multiple ethnic backgrounds, “Universal Genetic Carrier
Screening” is utilized
– Screens for over 100 autosomal recessive genetic conditions
– 1/3-1/5 individuals are carriers of these conditions
– Same cost as in individual disease carrier test
Aim of Counseling Regarding
Prenatal Diagnosis
• Supply at risk families with information so they can make informed
choices regarding pregnancy
– Provide a definitive answer for condition in question which allows for:
• An accurate diagnosis to provide a prognosis, management, and recurrence risks
which allows for family to either continue or end a pregnancy
• Providing reassurance to at risk families when result is normal
• Allowing couples to prepare psychologically for the birth of an affected child
• Helping the health care professional plan delivery, management and care of an
affected child
• Providing risk information to couples to assist in making decisions regarding their
reproductive future: PGD, egg/sperm donors, adoption, natural pregnancy with
diagnosis, no children
• Important points to question/inform patient
– Can condition be adequately screened for/diagnosed
– Will this information help them in any of the above ways such that it
outweighs the risk of the procedure?
– No test can guarantee a “healthy baby”
Neonatal/Pediatric Genetics
Indications for Genetic Referral
in Neonatal/Pediatric Setting
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Developmental delay or mental retardation
Dysmorphic features
Under or overgrowth
Failure to thrive
Seizure disorder of unknown cause
Hypotonia
Abnormal or ambiguous newborn screening results
Birth defect - either single or multiple
Ambiguous genitalia
Family history of genetic or chromosomal condition
Physical Examination
• Done by Medical Geneticist (MD)
– Looking for dysmorphic features- subtle or distinct
– Anthropomorphic measurements
– Photos of other family members
• Some findings are familial---does not mean it is not a
syndrome!
– Some findings are common---seen in 1-5% of the
population (normal variant)
Dysmorphology Exam
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Head Shape/Hair pattern
Ocular measurements
Nose
Ears
Philtrum/Mouth/Palate
Maxillary region
Mandible
Chest/Back
Limbs/Hands/Feet
GU
Skin
Common findings: seen in
isolation 1-5% of population
Not so common anymore…
• 6-8 Café-au-lait macules, learning disability=
Neurofibromatosis
• VSD, failure to thrive, distinct nose= VCFS
Importance
• Identifies etiology
• Provides prognosis and appropriate medical
management recommendations
• Provides accurate risk assessment for
recurrence
– Isolated cleft palate or cleft lip
• Recurrence risk based on empiric data (3-5%)
– If syndromic, recurrence risk may be up to 50%.
• 22q11.2 deletion (DiGeorge syndrome), Van der
Woude, Stickler syndrome
Other tools….
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Karyotype
FISH for specific suspected syndrome
Gene specific testing for suspected syndrome
Chromosomal microarray
– Is now considered by many societies as a first-tier
clinical diagnostic test for individuals with
unexplained developmental delay/intellectual
disability (DD/ID), autism spectrum disorders
(ASD), or multiple congenital anomalies (MCA)
Newborn Screening –
More Than
“The PKU Test”!
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CYSTIC FIBROSIS
ENDOCRINE CONDITIONS: Congenital adrenal hyperplasia
(CAH)*± • Congenital hypothyroidism*
HEMOGLOBIN CONDITIONS:Sickle cell disease and other
hemoglobinopathies*
METABOLIC CONDITIONS:
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AMINO ACID CONDITIONS : Homocystinuria* •
Hyperphenylalanemia, including • phenylketonuria (Pk )
Tyrosinemia*
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FATT y ACID OxIDATION CONDITIONS : Carnitine
uptake defect • Carnitine palmitoyl transferase I deficiency
(CPT I)* • Carnitine palmitoyl transferase II deficiency (CPT
II) • Multiple acyl-CoA dehydrogenase deficiency •
(MADD) Short chain acyl-CoA dehydrogenase deficiency •
(SCAD) Medium chain acyl-CoA dehydrogenase deficiency •
(MCAD)± Long chain 3 hydroxyacyl-CoA dehydrogenase •
deficiency (LCHAD)*± Very long chain acyl-CoA
dehydrogenase • deficiency (VLCAD)*±
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ORgANIC ACID CONDITIONS : Beta-ketothiolase
deficiency • (BkD)± Glutaric acidemia, Type I (GA I)* •
Isobutyryl CoA dehydrogenase deficiency • (IBD)±
Isovaleric acidemia • (IVA)* ± Malonic aciduria • Maple
syrup urine disease • (MSuD)± Methylmalonic acidemias
(MMA/8 types)± • Propionic acidemia • (PA)*± 3-Hydroxy3-methylglutaryl CoA lyase • deficiency (HMG)* 2-Methyl3-hydroxybutyryl CoA dehydrogenase • deficiency
(MBHD)* 2-Methylbutyryl CoA dehydrogenase • deficiency
(2MBC)* 3-Methylcrotonyl CoA carboxylase deficiency
(3MCC) • 3-Methylglutaconyl CoA hydratase deficiency
(3MGH) • Multiple carboxylase deficiency
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UREA CyCLE CONDITIONS : Arginase deficiency •
Argininosuccinate lyase deficiency (ASA)± • Citrullinemia±
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OTHER CONDITIONS : Biotinidase deficiency •
Galactosemia±
Newborn Hearing Screening
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1/1000 young children
have a major hearing
loss
50% of congenital
hearing loss is genetic
• Early diagnosis is key to
proper management
Pregnancy & Neonatal Loss
Chromosome Abnormalities
in Pregnancy Loss
• Approximately 25% of all clinically recognized pregnancies result in a loss
• <20 weeks = miscarriage
– Up to 50% are due to chromosome aneuploidy
• Most are due to nondisjunction with little increased risk of
recurrence
• However, karyotyping can be indicated in repeat pregnancy loss
since 2-5% of couples have a chromosomal abnormality causing
the increased RR
• >20 weeks = stillbirth
– 5% are due to chromosome abnormalities
– However, some of these do increase the RR and when no other cause is
known it is recommended to consider karyotype and/or microarray
Importance of a Genetic
Workup
• Can allow for a diagnosis which will answer
some of the most important questions a parent
will have
– Why?
– Will this happen again?
– Was it my fault?
• Therefore workups and often autopsies are
essential
Grief and Bereavement
• Pregnancy loss is the same to the majority of parents, if not worse, than any
other type of death
• It is extremely important to encourage, respect, and promote proper
grieving of a loss no matter how early
– It’s often a loss of dreams/hopes/expectations
– Avoid comments that take away from the current situation: you can
have another one, at least it was early, etc
• Important to:
– See, hold, spend time with the baby/body
– Take photos, they can always be kept in patient chart if not ready to
take them home
– Name the baby, memorialize the baby in some meaningful way to the
family
– Encourage the family to recognize their spiritual or religious beliefs
– Discuss cremation/burial options
• Offering gentle and beautiful
photography services in a
compassionate and sensitive
manner
• Work done by professional
photographers who volunteer their
services and are trained in this
specific area
– Photographers will work with
families in order to fit their needs
and desires
• Soft, gentle heirloom photographs
of these beautiful babies are an
important part of the healing
process
• They allow families to honor and
cherish their babies, and share the
spirits of their lives
• www.nowilaymedowntosleep.org
Perinatal Hospice
“When the prenatal diagnosis of a lethal fetal anomaly has
been established, some patients choose to continue their
pregnancies. We propose a model of care that incorporates
the strengths of prenatal diagnosis, perinatal grief
management, and hospice care to address the needs of these
families.”
—Hoeldtke NJ, Calhoun BC. "Perinatal Hospice." Am J Obstet Gynecol. 2001
Sept;185(3)525-9
• Medical, emotional, and spiritual support through pregnancy,
labor, birth, life and death
• Variety of services to help parents define a birth vision they
are comfortable with
• Families may choose any of the services that fit their needs
“Regardless of the length of a baby's life or duration of
illness, it is their lifetime. Both the infant and family
deserve skilled and compassionate attention to their
plight; a safety net throughout the experience; a palliative
care approach, which emphasizes living fully those days,
hours, and even moments.”
—Sumner LH. Taking palliative care into pregnancy and
perinatal loss. National Perinatal Association Bulletin.
2004;5(2).
A news clip on Now I Lay Me Down To Sleep.
http://www.msnbc.msn.com/id/21134540/vp/23481435#23481435
Thank You
Questions?