Congenital abnormalities Flashcards
Define congenital abnormalities
Abnormalities that exist at or before birth
Name the 4 types of clinically significant congenital abnormalities
1) Malformation
2) Disruption
3) Deformation
4) Dysplasia
What is malformation?
A morphologic defect of an organ, part of an organ, or larger region of the body resulting from an intrinsically abnormal developmental process
What is disruption?
A morphologic defect of an organ, part of an organ, or larger region of the body resulting from the extrinsic breakdown of, or an interference with, an originally normal developmental process
What is deformation?
An abnormal form, shape, or position of a part of the body caused by mechanical force
What is dysplasia?
An abnormal organisation of cells into tissue(s) and its morphologic result(s) - a process and consequence of dyshistogenesis
Define teratogenesis
A process whereby an abnormality is induced in a developing organism during uterine life by a foreign agent (teratogen)
What abnormalities could an excess of vitamin A cause?
Cleft palate, mandibular hypoplasia, heart defects
What could alcohol cause?
Fetal alcohol syndrome
What abnormalities could rubella cause?
Deafness, cataracts, retinal dysplasia, microcephaly
What abnormalities could cytomegalovirus and toxoplasma gondola cause?
Microcephaly and micropthalmia
What abnormalities could X-ray cause?
Microcephaly, spina bifida, cleft palate
What abnormalities could valproate cause?
Neural tube defects, facial defects, limbs
When is the foetus at greatest risk of damage from a teratogen?
3-16 weeks; the period during which multiple systems are developing
Why is the embryo not at risk from teratogens at 0-2 weeks?
It either repairs or dies
What happens to the risk of structural abnormality during gestation?
Look at graph on slide 22
What happens to the risk of functional abnormality during gestation?
Look at graph on slide 22
What can influence the teratogenicity of a substance?
1) Teratogen must contact developing embryo/fetus
2) Timing or period of development at point of exposure
3) Duration and dosage of exposure
4) Fetus susceptibility eg. due to genotype
How can a substance be teratogenic?
1) Mutational changes in DNA sequences
2) Interruption of DNA or RNA synthesis
3) Failure of normal cell migrations
4) Failure of normal cell-to-cell interactions
5) Interference with cell differentiation
6) Chromosomal abnormalities leading to structural or quantitative changes in DNA
What are Wilson’s six general principles of teratology?
The final manifestations of abnormal development are death, malformation, growth retardation and functional disorder.
Susceptibility of the conceptus to teratogenic agents varies with the developmental stage at the time of exposure.
Teratogenic agents act in specific ways (mechanisms) on developing cells and tissues in initiating abnormal embryogenesis (pathogenesis).
Manifestations of abnormal development increase in degree from the no-effect to the totally lethal level as dosage increases.
The access of adverse environmental influences to developing tissues depends on the nature of the agent.
Susceptibility to a teratogen depends on the genotype of the conceptus and on the manner in which the genotype interacts with environmental factors.
Define teratology
Refers to the study of the types, patterns, mechanisms and causes of congenital abnormalities
What are the two types of congenital diaphragmatic hernia?
Bochdalek type is most common (posterolateral diaphragm)
Morgagni hernia are less common (anterior part of diaphragm)
Commonly due to diaphragmatic malformation
What are some presentations of fetal alcohol syndrome?
Midline facial abnormalities (maxillary)
Absent philtrum
Thin top lip
Thick/pronounced epicanthic folds
Flattened nose
Short palpebral fissure
Heart defects
Neural issues: Behavioural and developmental
Describe the 3 different types of congenital limb defects
Amelia = no limb Phocomelia = "seal limb" Meromelia = part limb
What can be some causes of congenital limb defects?
- Prescribed medication (e.g. thalidomide)
- Dietary (e.g. Retinoids or Vitamin A derivatives)
- Mechanical (e.g. Amniotic bands occlude blood supply)
What are the 3 cardiac congenital abnormalities?
1) Tetraology of Fallot
2) Common/persistent truncus
3) Transposition of the great vessels
What can increase the risk of cardiac defects?
Associated with teratogens e.g. tobacco smoke
Obesity and pre-existing maternal diabetes may increase risk
Defects (e.g. septal) can be associated with neural crest cell migration issues
Name some neural tube defects
Anencephaly, myeloshisis, meningocoele
What can increase the risk of neural tube defects?
Associated with dietary deficiency of folic acid (Vitamin B9)
Associated with teratogens such as valproate, X-ray
May be seen more often in mothers with pre-existing health conditions e.g., diabetes, obesity
What are some cranial, ocular and auricular defects?
Microcephaly Anopthalmia Micropthalmia Anotia Microtia
What teratogens can cause cleft palate and lip?
Antiseizure drugs, retinoids, corticosteroids, tobacco smoking
May result from abnormal neural crest cell migration
How many live births does cleft lip alone affect vs. cleft palate and lip?
Cleft lip alone (1:2800 live births)
Cleft palate and cleft lip (1:1600)
What are some presentations of pharyngeal arch one maldevelopment?
Mandibulofacial maldevelopment/dysostosis(zygoma, mandible & maxilla)
Downward slanting palpebral fissure
Malformed ears (pinna)
Possible conductive deafness
Treacher-Collins or Pierre Robin Syndrome
Autosomal dominant condition
Can be teratogen-induced(e.g., alcohol, retinoids, maternal diabetes
