More Related Content Similar to Genetics in a Pediatric Setting Similar to Genetics in a Pediatric Setting (20) 1. © The Children's Mercy Hospital, 2014. 03/14
Caitlin Lawson
Certified Genetic Counselor
June 27, 2014
Genetics in a Pediatric
Setting
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Genetic Counseling
• Genetic counseling is the process of helping people
understand and adapt to the medical, psychological
and familial implications of genetic contributions to
disease. This process integrates the following:
– Interpretation of family and medical histories to assess
the chance of disease occurrence or recurrence.
– Education about inheritance, testing, management,
prevention, resources and research.
– Counseling to promote informed choices and adaptation
to the risk or condition.
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Areas of Practice
• Prenatal
– Concerning family histories, ethnicity-based carrier
screening, or abnormal ultrasound/screening tests
• Pediatrics
– Children/families with known disorders, developmental
disabilities, dysmorphism, biochemical abnormalities
• Specialties
– Cardiology, Dermatology, Neurology
• Cancer
– Assessment of cancer risk, coordination and counseling
regarding test results
• Industry/Laboratory
• Research
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Catalog of Genetic Diseases in Humans
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Modes of Inheritance
• Chromosomal
– Aneuploidy
– Microdeletions/microduplications
• Single gene disorders
• Mitochondrial
• Multifactorial
– Genetics + environment
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Burden of Genetic Disease in
Pediatric Hospital Admissions
8.5% Single gene and chromosomal
13.9% Multifactorial (i.e. congenital heart
defect)
32.6% Genetic predisposition (i.e. asthma,
cancer)
8.4% Multiple causes, often genetic (i.e.
mental retardation)
63.4%
Am J Hum Genet. 67. A113. 2000. (Rainbow Babies and Children’s Hospital)
9. Chromosomes
Microdeletions/Microduplications
Genes
Similar to looking at books lined up on a shelf;
can see if there is an extra book or possibly
one missing. High resolution chromosome
analysis: detects large changes or
rearrangements.
Similar to looking for missing or extra chapters or
paragraphs. FISH testing: specific. Microarray: non-
specific, will look through the entire collection of
books for missing or extra chapters
Similar to proofreading a sentence for a
misspelled or missing word. Gene
sequencing: specific; must know which
sentence you want to analyze for a change
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Turner Syndrome
• Short stature
• Congenital heart defect
– (30-50%, abnormal aorta
coarctation is most
common)
• Webbed neck/low hairline
• Lymphedema of hands
and feet
• Skeletal abnormalities
• Kidney abnormalities
• Typically have normal
intelligence but may have
developmental delay or
social difficulties
• NOT associated with
advanced maternal age
• May be mosaic
– 45,X cell line in
combination with another
– Does NOT predict less
severe phenotype
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CHARGE Syndrome
• Coloboma
• Heart defect
• Choanal Atresia
• Retarded growth and development
• Genital abnormalities
• Ear abnormalities
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Autosomal Dominant
Inheritance
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Autosomal Recessive
Inheritance
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Duchenne Muscular
Dystrophy
• Proximal muscle
weakness
– Often with calf
hypertrophy
• Progressive
– Typically wheelchair
dependent by 12 years
• Dilated cardiomyopathy
• Carrier mothers have an
increased risk for dilated
cardiomyopathy
• Less severe phenotype:
Becker muscular
dystrophy
– Same gene, different
type/location of mutation
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Reproductive Risks
• Autosomal recessive (CF)
– NBS (40) Mutation panel (97) CFTR
gene sequencing Deletion testing
• X-linked (Becker MD)
• Autosomal dominant (cancer)
• Chromosomal (maternal age: 38)
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Missouri State Newborn
Screening for Hurler
Syndrome
(mucopolysaccharidosis
type I)
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Hurler Syndrome (MPS1)
• 1/100,000 incidence for severe form
• Features: Coarse facies, frequent upper
respiratory infections, short stature,
corneal clouding, macroglossia,
hepatosplenomegaly, intellectual
disability, hearing loss, dysostosis and
kyphosis
– Storage of GAGs within the oro-
pharynx with associated enlargement of
the tonsils and adenoids can contribute
to upper airway complications, along
with narrowed trachea, thickened vocal
cords, redundant tissue in the upper
airway, and an enlarged tongue
– Death from cardiorespiratory failure
typically occurs by first or second
decade
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Treatment for Hurler
Syndrome
• Enzyme replacement therapy
(Aldurazyme®)
– Weekly infusion
– Does not cross blood/brain barrier
– Cannot prevent CNS complications
– Can improve sleep apnea and pulmonary
function and decrease liver size
• Hematopoietic Stem Cell Transplantation
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MO NBS for Hurler Syndrome
• Began in January 2013
• Assay measures average IDUA enzyme
activity level
• Pseudodeficiencies
– Mutation alters the protein product or changes
the gene's expression, but does not cause
disease
– Common in African Americans
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Ethical Considerations
• DNA testing not always straightforward
• Higher rate of pseudodeficiency than
expected
• Severe and attenuated forms
• Treatment has limited efficacy
• What is follow up for children whose DNA
results are inconclusive and enzyme level
is borderline?
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Indications for Referral for
Genetics Services
• Metabolic, biochemical
disorders
• Multiple miscarriages or
stillbirths
• Infertility
• Prenatal counseling
• Consanguinity, incest
• Prenatal diagnosis
• Known or presumed
congenital anomalies
• Acknowledged familial
disorders
• Known inherited
disorders
• Known or suspected
chromosome anomalies
