Lecture 13 – Congenital and Genetic Disorders
Congenital Defects: (Birth defect)
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This includes genetic/inherited disorders, developmental disorders
1. present at birth or 2. shortly after
Ex 1. spina bifida, cleft palate
2. Heart, kidney disorders
Causes: (1 & 2 more common)
1. Genetic factors
- Ex. Single gene, multifactorial inheritance or chromosol aberrations
2. Environmental factors during embryonic or fetal development
- Ex. Maternal disease, infections or drugs taken during pregnancy
3. Rarely intrauterine factors
- EX. Fetal crowding, entanglement with umbilical cord
Genetic Defects:
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Defect passed from one generation to another by genes (x or y chromosome,
not somatic)
- Some are apparent at birth so can be classified as “congenital”
1. Single Gene Disorder
- Caused by a defect in one gene
- Passed on chromosome to subsequent generations
- Follows inheritance patten for that gene
2. Chromosomal Disorders
- Error during meiosis
- Common cause of spontaneous abortion
- Ex trisomy, turner’s syndrome, Klinefelter’s syndrome
3. Multifactorial Disorders
- Can be polygenic (caused by multiple genes) or inherited tendency combined
with exposure to environmental factors
- Ex. Atherosclerosis
Punnet Squares:
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Designed to predict the percentage risk factor for offspring to carry the genetic
defect or suffer from the defect
Based on patterns of inheritance termed Mendelian laws or patterns
Includes recessive and dominant patterns
Recessive genes are lower case and dominant genes are capitals
Autosomal Recessive Disorders:
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Both parents must pass on the allele for disorder.
o Parents may be heterozygous and unaffected (carriers)
o Parents may be homozygous and affected (need to have both allele)
Male and female children are affected equally.
Homozygous recessive child has the disorder.
Heterozygous child - No clinical signs of disease, child is carrier
Ex. Cystic fibrosis, PKU (phenylketonuria metabolic disorder), Tay Sachs
disease
Autosomal Dominant Disorders:
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Inheritance of one allele causes disorder (only one parent needs to carry
allele)
No carries = unaffected persons do not transmit the disorder
Some conditions become evident later in life
o Delayed lethal genotype - Allele for disorder may have been passed on
to next generation before diagnosis of disease parent
Ex. Adult polycystic kidney disease, Huntington’s disease, familial
hypercholesterolemia, Marfan’s syndrome
X-linked Recessive Disorder:
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Allele carried on the x chromosome but not the Y chromosome
Manifested in heterozygous males lacking the matching unaffected gene on
the Y chromosome
Heterozygous females are carriers
Homozygous recessive females may be affected
Inheritance may appear to skip generations
Ex. Duchennes muscular dystrophy, classic hemophilia
X-linked Dominant Disorders:
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Heterozygoud males and females affected
Reduced penetrace in females
Ex. Fragile X syndrome
Most common genetic cause of cognitive defects
Effects are variable and realted to the extend of mutation of the allele
Teratogenic Agent:
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Enviromental Agent that produces abnormalities during embryonic or fetal
development ex. Radiation, chemicals, drugs, infectious organisms
Most serious of this takes place during organogenesis
15 to 60 days post censeption
TORCH infections – tested for pre natal
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Toxoplasmosis, Other, Rubella, Cytomegalovirus, Herpes simplex
o Other stands for chicken pox and syphilis
Developmental Disorders:
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Results from teratogenic agents, premature birth, difficult delivery
Diagnostic tools: For carriers its tested either in, prenatal, immediately after birth, later
in life when abnormality suspected
Who is tested?
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Strong history of specific disease
Someone who previous gave birth to a child with an abnormality
Women over 35 yrs
- Screening programs to identify carriers, testing population having increased risk for a
certain disorder ex. Ashkenazi Jews for Tay Sachs disease
-Benefits: Genetic counselling available to assist induvials at risk
Methods of Prenatal Testing & Diagnosis
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Ultrasound - nuchal translucency
Maternal Serum Screening – AFP, hCG, estriol
Amniocentesis
CVS – chorionic villus sampling
PUBS – percutaneous umbilical blood sample
Cell free DNA (blood test)