L7: principles of congenital malformation Flashcards
What is teratology?
Study of monsters
teratology deals with
It deals with causes, mechanisms and patterns of abnormal
Why is organogenesis is a critical period (embryonic period)?
Because most organs are formed so a lot of things can go wrong
Why is it important to know about birth defects?
Because these are the leading cause of infant mortality
birth defect could be
May be structural, functional (like renal agenesis), metabolic, behavioral or hereditary
most birth defects are associated with what stage
Most are associated with early stages of development
The term ‘Teratology’ was coined by
Etienne Geoffrey St. Hilaire Literal
What is a teratogen?
A teratogen is any agent that may cause developmental disruptions
What does rubella virus cause?
that rubella virus is a cause of an identifiable syndrome of abnormal development,
cataracts, cardiac defects and deafness
what is the story of thalidomide and the medical community?
In early 1960s pregnant woman use to take thalidomide to prevent nausea, but this
caused the baby to be born without limbs > sensitized the medical community
How did Anatomical accuracy of ancient art help us?
Anatomical accuracy of ancient art often makes it possible to diagnose specific condition
or syndrome
Chalk carving from New Ireland in South Pacific showing dicephalic, dibrachic conjoined
twins. Note also the “collar” beneath the heads. (the actual disease was what)?
This “collar” is a representation of cystic hygroma colli (a benign neoplastic cystic tumor
of the neck of lymphatic origin) shown in the photograph of a malformed fetus.
The bird-boy of Paré (1520) represented much more imaginative, hybrids of humans and
Animals. the disease was…
Stillborn fetus with malformations those were sirenomelia (fused legs). Compare with the
lower part of the bird-boy.
What causes sirenomelia
Gestational Diabetes may induce abnormal migration of mesoderm leading to fused legs
What are the Major causes of congenital malformations?
- Multifactorial 55% > several causes =we do not know
- genetics 30%
- environmental 15% > lifestyle, drugs abuse, alcohol
why is the embryonic period the most critical period?
• Organogenesis > there is no time where the baby is 100% safe
Rubella virus common malformation are
Cataract and heart malformations Deafness
Thalidomide
Reduction defects of limbs
Androgenic steroids
Female external genitalia
Coumadin
Nasal hypoplasia
Anticoagulants
possible mental retardation
Radioiodine therapy
Fetal thyroid deficiency
Tetracycline(antibiotic)
- Staining of enamel in primary teeth
- Staining of crowns of permanent teeth
XO (missing X), phenotype&clinical complement?
Phenotype: Immature female
Clinical Complement: Turner syndrome
XXY (extra X)
Phenotype: Male
Clinical Complement: Klinefelter syndrome
XYY (extra Y)
Phenotype: Male
Clinical Complement: Normal appearance; reputed difficulty, with impulsive behavior
XXX (extra X)
Phenotype: Female
Clinical Complement: Normal appearance, mental retardation
(1/3rd of cases), fertile (in many cases)
Define Trisomy?
- These are usually fatal.
* 3 copes of an autosomal chromosome
what is the most common abnormalities of autosome numbers?
trisomy
When does trisomy increase?
These occur with increasing frequency as maternal age increases.
example of trisomy
- Trisomy 13 (Patau syndrome)
- Trisomy 18 (Edwards syndrome)
- Trisomy 21 (Down syndrome)
Describe Infants condition if they have Trisomy 13 (Patau syndrome) or Trisomy 18 (Edwards
syndrome)?
Infants with Trisomy 13 (Patau syndrome) and Trisomy 18 (Edwards syndrome) are
severely malformed and mentally retarded and usually die early in infancy.
Describe Infants condition if they have Trisomy 21 (Down syndrome)?
Infants with Trisomy 21 (Down syndrome) are typically mentally retarded
What are the characteristics of Trisomy 21 (Down syndrome)?
o facial features
o heart defects
o intestinal anomalies
o broad hands
o the palmer surface is marked by transverse simian crease.
AUTOSOMAL DOMINANT
need one copy to show phenotype
examples of autosomal dominant
- Achondroplasia
- Aniridia
- Polycystic kidney disease (adult-onset, type 3)
Achondroplasia
Dwarfism > shortening of limbs
Aniridia
Absence of iris(usually not complete)
Polycystic kidney disease
adult-onset, type 3
Numerous cysts in kidneys
AUTOSOMAL RECESSIVE
need Two copy to show phenotype
examples of autosomal recessive
- Albinism
2. Polycystic kidney disease (prenatal type 1)
Albinism
Absence of pigmentation
Polycystic kidney disease (prenatal type 1)
Numerous cysts in the kidneys
X-LINKED RECESSIVE
males are more susceptible
examples of X-LINKED RECESSIVE
- Hemophilia
2. Hydrocephalus
Hemophilia
Defective blood clotting
Hydrocephalus
Enlargement of cranium
Rubellavirus (fetal)
Disease: German measles
Congenital defects: Cataracts, deafness, CVS defects, growth retardation
Cytomegalovirus
Disease: Cytomegalic inclusion
Congenital defects: Cephalic deformities, intrauterine growth retardation
SPIROCHETES: Teponema pallidum
Disease: Syphilis
Congenital defects: Dental anomalies, deafness, mental
retardation, skin & bone lesions, meningitis
PROTOZOA: Toxoplasma gondi
disease: Toxoplasmosis
Congenital defects: Cephalic deformities, mental
retardation, prematurity
Hyperthermia (High temperature)
Anencephaly, spina bifida, intellectual disability
Ionizing radiation
Microcephaly(small head), spina bifida (failure to close the caudal pore), cleft palate, limb defects
Alcohol
Growth & mental retardation, facial & trunk malformations
Anticoagulants
Skeletal abnormalities, nasal hypoplasia, anomalies of the eyes, neck, CNS
Anticonvulsants
Neural tube defects, mental retardation, poor growth, facial defects
Antithyroid drugs
Fetal goiter, hypothyroidism
Chemo-therapeutic agents
Variety of major anomalies throughout body
Industrial solvents
Spontaneous abortion, prematurity, low birth weight, heart,
craniofacial, and neural tube defects
Lead
Growth retardation, neurological disorders
Lithium
Heart anomalies
Organic mercury
Mental retardation, cerebral atrophy, spasticity, blindness
Retinoic acid
Defects related to derivatives of neural crest
Streptomycin
Hearing loss, auditory nerve damage
Tetracycline
Hypoplasia and staining of tooth enamel, staining of bones
Thalidomide
Limb defects, ear defects, cardiovascular anomalies
Valproic acid
Neural tube defects; heart, craniofacial, and limbs
Androgen
Masculinization of female genitalia, accelerated genital development in males
Diethylstilbestrol
Malformation of the uterus, uterine tubes, and upper vagina; vaginal cancer; malformed testes
Maternal diabetes
Various malformations; heart and neural defects most common
Maternal obesity
Neural tube defects, heart defects, omphalocoele
what are Screening tools?
- Maternal serum screening-Serum alpha fetoprotein
- Amniocentesis
- Chorionic villus
Maternal serum screening-Serum alpha fetoprotein
sample of mother blood > indicate
down syndrome
Amniocentesis
analyzing sample of ammonia attic fluid
Chorionic villus
sampling sample of the chorion (placenta)
What is Clubfoot?
- It a disease caused by decrease or absence of amniotic fluid
- Structural anomaly
What is a teratogen?
• It is an agent that can produce a congenital anomaly or raise the incidence of an
anomaly in the population
What does Teratogenicity of an agent depend on?
- critical periods of development
- the amount of the agent or dose of the drug
- genetic constitution (genotype) of the embryo
