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Genetics for Nurses in Pediatric Disciplines


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Title: Genetics for Nurses in Pediatric Disciplines

Genetics for Nurses in Pediatric Disciplines
  • A guide to recognition and referral of congenital
    and genetic disorders
  • Golder N. Wilson MD PhD,1 Vijay Tonk PhD,2
  • 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 or Ms. Joyce
    Hooker at

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
Think genetics when something is unusual or
  • Case A 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// 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 that lists testing (when
    available) for the particular genetic disease (go
    to the clinical laboratory section and search by
    disease name

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
  • 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

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
  • Several genes (plus environment) are abnormal
    (multifactorial disorders or susceptibilities)
  • A gene (DNA to RNA to protein) is abnormal
    (Mendelian disorders

Categories of genetic or congenital disease
  • 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
    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
  • Other inherited anemias can be related to
    different abnormal globin alleles (C, D, E,

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 gt6000 Mendelian diseases thus relate to a
    similar number of different genes and abnormal
  • 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

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.,
Chromosomal diseases imbalance multiple genes
and cause multiple birth defects Karyotype
REYDAR of common pediatric presentations
Recognition ? Category ? Referral ? Medical home
  • Case 1N, 3Nnewborns with poor feeding, unusual
  • Case 4NNewborn with deterioration and lethargy
  • Case 5KChild with hypotonia and motor delays
  • Case 6KFirst-grader with school problems
  • Case 7KBoy with tall stature
  • Case 8KGirl with intermittent acidosis and
  • (see Chapter 1)

Case 1N. Newborn with feeding problems(see
Chapter 1 of primer)A term female infant
exhibited slow growth in the last trimester of
pregnancy but had normal ultrasound studies.
After normal delivery and borderline low birth
weight (5 lbs), the mother reported difficulty
breast-feeding. Lactation education and
reassurance were given and the infant was
discharged with mild jaundice and a weight loss
of 5 from her birth weight. Was this
management appropriate?What additional history
might have been helpful?
REYDAR of common pediatric presentations
Recognition to category to referral and
Poor breast-feeding may signal syndromes or
congenital disorders
Case 1N (cont) Important history was that this
child was mothers second--her child was the
problem, not her breast-feeding. The childs low
muscle tone and subtle facial changes
(down-slanting palpebral fissures, broad nasal
bridge, down-turned corners of the mouth) led to
evaluation after discharge with chromosome
studies that showed deletion of the number 4
short arm (4P- or Wolf-Hirschhorn syndrome.
Recognition of HP signals was the key to REYDAR,
not knowledge of a rare disease.
A birth defect (VSD) plus other signs
  • Case 3N A term male infant with a heart murmur
    was found to have a ventricular septal defect
    without failure but had continuing lethargy, low
    muscle tone, poor latch for breast-feeding and
    difficulty stooling. What else should be

  • The infants facial appearance was slightly
    unusual and raised the question of Down syndrome
    (OMIM 190685), which would explain the low
    muscle tone and poor feeding. Single palmar
    creases were noted on the hands as well as wide
    spaces between the first and second toes. What
    testing would be most useful in determining the
    childs diagnosis?

  • Routine chromosome analysis (karyotype) will show
    the extra chromosome 21 that is characteristic of
    Down syndrome which normally requires at least
    5-7 days for results.

  • Now a rapid FISH test is available that does not
    require stimulation of white blood 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)

  • RULE Do not blame neonatal feeding problems on
    inexperience/adjustment without considering a
    congenital/genetic disorder
  • RULE Consider congenital/genetic disorders in
    children with several physical variations (minor
    anomalies) and/or unusual facial appearance

Case 6K. A first-grader with school problems
A 6-year-old girl is having trouble keeping up in
the first grade because of distractibility and
poor comprehension. She had some problems
breast-feeding and later needed speech therapy.
Her school nurse noted a somewhat unusual facial
appearance with narrow eyes, long face, and
prominent nose she also had long fingers and a
faint heart murmur. The childs teacher felt she
was a discipline problem due to attention deficit
or conduct disorder and suggested possible
medication therapy. Do you agree?
  • The subtle facial changes, speech delay, and
    school problems suggest mild mental
    disability--such children may be labeled as
    unmotivated or hyperactive unless the underlying
    congenital problem is recognized. This child had
    the Shprintzen-DiGeorge spectrum (OMIM 192430),
    proven by FISH testing showing submicroscopic
    chromosome 22 deletion (her parents were normal).
    Referral to cardiology showed a small cardiac
    defect and arrythmia medication was needed, but
    not for the learning problem.

  • RULE Look for additional physical variations
    (minor anomalies like single palmar crease) in
    children with apparently isolated birth defects
    because syndromes imply multiple problems and
    higher genetic risks
  • RULE School problems may reflect cognitive
    disabilities due to genetic conditions rather
    than behavior or psychosocial problems.

Chromosome disorders
  • Miscarriages (50-60), liveborn children (0.5),
    cancer tissue (many have diagnostic changes)
  • Over 200 pediatric 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
  • 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
  • See Chapter 7 for more information

Case 4N Sudden deterioration and unusual odor in
a newborn after 24 hours of feeding.
  • A term newborn male with appropriate birth weight
    had an uncomplicated vaginal delivery with good
    Apgar scores. The child fed avidly for 24 hours
    but slowly become lethargic and less active. The
    nurse noted jaundice and documented a cutaneous
    bilirubin of 8.0 mg , mostly indirect. Review of
    the family history showed that the couple had 3
    living children with 2 prior infant deaths of
    unknown cause they came from the same small town
    in Mexico. The nurse also detected an unusual
    sweet smell to the urine and notified the
    pediatrician when the child became jittery and
    would not feed. What is the most likely disease

Inborn errors of metabolism
  • Metabolic diseases in children can have acute,
    intermittent, or insidious presentations. Unlike
    diabetes mellitus or metabolic syndromes in
    older children with obesity, early onset
    metabolic disorders are often due to abnormal
    genes that encode defective enzymesinborn errors
    of metabolism. Acute inborn errors involve
    derangements of small molecules and often
    manifest when a newborn is removed from the
    maternal metabolism (delivery) and required to
    break down foodstuffs on its own. Many acute
    metabolic disorders have similar symptoms of
    lethargy, low tone, and jitteriness progressing
    to coma due to low blood sugar, acidosis,
    inability to make energy, or high ammonia. What
    screening tests are indicated to investigate an
    acute metabolic disorder?

Inborn errors of metabolism
  • The standard newborn screen in Texas detects the
    acute metabolic disorders phenylketonuria (PKU--
    OMIM 261600) and galactosemia (OMIM 230400) as
    well as sickle cell anemia (OMIM 603903),
    congenital adrenal hyperplasia (OMIM 201910,
    others), and hypothyroidism (OMIM 218700,
  • The expanded or supplemental newborn screen
    (employing in part an acylcarnitine profile) uses
    mass spectrometry to detect up to 50 additional
    acute metabolic disorders and is being adopted by
    most states.
  • The supplemental screen along with blood sugar,
    electrolytes, pH, and ammonia was obtained in
    this infant, showing a low sugar (45 mg ),
    elevated anion gap (sodium plus potassium
    concentration minus chloride and bicarbonate ?
    12-14), acidosis (pH lt 7.2), and abnormal
    acylcarnitines. These findings plus certain
    elevated blood amino acids (leucine, isoleucine,
    valine) suggested a diagnosis of maple syrup
    urine disease and led to successful dietary
    treatment of the metabolic disorder

Inborn errors of metabolism
  • Over 300 disorders with overall frequency 1 in
  • 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
  • Early recognition is key before organ damage
    occurs from acidosis, seizures, or chemical
    build-up dietary treatment is often available

  • RULE Suspect acute metabolic disorders in
    normal-appearing infants who decompensate after
    feeding look for hypoglycemia, acidosis, or high
  • RULE The lack of a family history does not
    exclude a genetic disordersuspect new gene
    mutations or chromosome aberrations.

Case 7KA boy with tall stature
. A pediatric nurse conducts a school physical
on a 6-year-old boy who is very tall for his age.
He has a height beyond the 97th centile despite
average weight and head circumference, and his
parents are not tall. The nurse notes other
findings including an aged facial appearance, lax
joints, heart murmur, and concave chest. The
nurse suspects a genetic condition, and documents
a family history
Case 6A, cont
  • The family history shows numerous relatives with
    heart problems on the fathers side. The father
    (individual III-2) is not unusually tall (5 10)
    and has no eye or heart problems. However, the
    fathers brother (individual III-1) developed
    aortic dilation and insufficiency at age 39, was
    6 5 tall, and had a lean build with flat feet
    and inguinal hernias.

Disorders with extreme tall stature (gigantism),
short stature (dwarfism), or failure to thrive
are often genetic
  • Diagnosis Marfan syndrome (154700)
  • Suspicion of the disorder led to protection from
    collision or high-intensity sports and led to
    cardiac studies demonstrating aortic dilatation.
    The boy and affected family members have a 50
    risk to transmit the disease with each child.

Case 9P. Adolescent female with unplanned
  • 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.

  • The fetal growth changes would be consistent with
    fetal alcohol syndrome but the severe
    microcephaly suggested anencephaly (OMIM 206500,
    others). Of growing importance in pediatrics is
    preconception care, illustrated here by the fact
    that folic acid taken early in pregnancy lowers
    the incidence of neural tube defects like
    anencephaly or spina bifida by 2/3. As with
    maternal diabetes, prevention must begin before
    planning the pregnancy since a missed period may
    not be noticed until 3-4 weeks after conception
    (after the primitive streak stage)

  • RULE 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

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)
Multifactorial Disorders
  • Most isolated birth defects like cleft palate,
    hypospadias, heart defects, spina bifida
  • Many common diseases like diabetes mellitus,
    hypertension, mental illness
  • 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. A term female infant to a 37-year-old mother
    with three prior children has a low birth weight
    and a poor latch for breast-feeding the first 24
    hours of life. Mother had first trimester
    maternal serum screening (quad screen) that was
    normal. Your assessment of the baby reveals an
    unusual facial appearance with a broad nose and
    extra skin folds on the neck. Based on the
    history, which of the following is the most
    likely reason for poor breast-feeding in this
  • Maternal incompetence
  • Autosomal dominant disorder in mother
  • X-linked recessive disorder in child
  • Chromosomal disorder in child
  • Multifactorial disorder in child
  • 2. Prior to receiving test results, the most
    important aspect of care along with evaluating
    the feeding problem is
  • Genetic counseling regarding recurrence risk
  • Genetic counseling regarding prenatal diagnosis
  • Supportive counseling for future mental
  • Supportive counseling for probable birth defects
  • Supportive counseling explaining the management

  • 3. A female infant demonstrates inconsistent
    bottle feeding and exaggerated jaundice with a
    total bilirubin of 14 at day 2 of life. Your
    assessment reveals the infant is less responsive
    than early on your shift, and you note decreased
    muscle tone with a poor suck. The prenatal
    history is normal except that the mother and
    father are from Pakistan and are second cousins.
    Which of the following conditions would be most
    likely in this infant?
  • Chromosome disorder
  • Biliary atresia
  • Inborn error of metabolism
  • Lactose intolerance
  • Multifactorial disorder
  • 4. As the infant is being evaluated, a
    grandparent brings documentation from Pakistan
    showing a prior child of this couple died with a
    diagnosis of maple syrup urine disease. Which of
    the following would resources would provide
    information on the inheritance of this disorder?
  • Online Mendelian Inheritance in Man
  • GeneTests
  • Alliance of Genetic Support Groups
  • ACOG

Questions 5-6
  • 5-6. 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.
  • 5. 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

  • 6. 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

Answers 1-D 2-E
  • Questions 1-2.
  • Difficulty breast feeding by an experienced
    mother should prompt concern about a congenital
    disorder. The history of advanced maternal age
    (gt 35) together with an unusual appearance in the
    child warrants consideration of a chromosome
    disorder. (answer 1D). First trimester quad
    screen plus ultrasound will detect as many as 87
    of fetuses with Down syndrome but sampling of
    fetal cells (e.g., chorionic villus sampling or
    amniocentesis) with karyotyping is required for
    definitive diagnosis of fetal chromosome

Answers 3-C 4-A
  • Questions 3-4
  • The difficulty feeding with progressive lethargy
    and family history of parental consanguinity
    (relatedness) suggest a metabolic disorder (see
    Chapters 2 and 10). Information on genetic
    disorders such as maple syrup urine disease can
    be found in Online Mendelian Inheritance in Man
    (enter OMIM in browser).

Answers 5-C 6-C
  • Questions 5-6
  • 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.