Teratology Flashcards
(57 cards)
define a teratogenic exposure and a birth defect
➢ A teratogenic exposure is any exposure to an
external agent or process capable of causing a birth
defect in a developing fetus.
➢ Birth defects, congenital malformation, and
congenital anomaly are synonymous terms used to
describe structural, behavioural, functional and
metabolic disorders present at birth
The history of the thalidimide disaster
-Thalidimide was first discovered in 1953 by Chemie Grunenthal
- Was discovered to be an anti-emetic Used by prgnant women
Thalidomide was marketed and
distributed in 46 countries around
the world using different names.
➢ For example, the drug was known as Distaval
in the UK and Australia, but was called
Softenon in Europe and Contergan in
Germany.
➢ Thalidomide became one of the world’s largest
selling drugs, and was marketed heavily and
advertised as completely safe right up until it
was eventually banned in November, 1961.
- soon after the release reports surfaced of patients developing peripheral neuropathy
- severe birth defects were also seen, thalidimide denied
-1961 that thalidomide was confirmed by two independent
clinicians, Widukind Lenz in Germany and William McBride in
Australia, - damage due to thalidimide was primarily seen in the limbs,face,genetalia,eyes,ears, and internal organs(IE kidney,heart,GIT)
- vertebral column damage was also seen in some survivors, and Facial palsies
Thalidomide causes damage to the developing
embryo in a short time sensitive window also
known as the “critical period.” which is 20-36 days after fertilization
History of rubella terotgenecity
-was first recognized in Germany in 1814 as a mild childhood illness characterized by a distinctive rash, fever, lymphadenopathy, arthralgia, and respiratory symptoms.
- when rubella is caught during pregnancy it cause a lot of problems for the fetus. such as spontanous abortion, fetal death, and infants with a constellation of anomalies including cataracts, heart defects, and hearing impairment.
-Rubella virus was first identified as a teratogen in 1941 by Gregg
The teratogenicity of herpes simplex virus
doublestranded DNA virus, belonging to the family of
Herpesviridae transmitted across mucosal membranes and nonintact skin, that migrate to nerve tissues, where they persist in a latent state.
-HSV1 predominates in orofacial lesions and is normally found in the trigeminal ganglia
- HSV2 found in lumbosacral ganglia
-In women it causes blistering and ulceration of the external genitalia and cervix leading to vulval pain, dysuria, vaginal discharge, and local lymphadenopathy.
-infections during pregnancy may be transmitted to newborns:
HSV-1 and HSV-2 may cause eye or skin lesions, meningoencephalitis, disseminated infections, or foetal malformations.
-risk of fetus getting infected with herpes seems to increase during the 3rd trimester
-In this case there may not be sufficient time for the development of maternal IgG and their passage to the fetus, and the risk of neonatal infection is 30 to
50% .
-infection in the first trimester seems to be linked to an increase in spontaneous abortions and restricted fetal intrauterine growth
-Infants infected intrapartum or postnatally by HSV can be divided into three major categories:
1- HSV localized to skin,eyes, and/or mouth
2-HSV encephalitis with or without eyes, skin or mouth involvement, causes neurologic morbidity among the majority of survivors
3- Disseminated HSV, which manifests as severe multiorgan dysfunction and has a mortality risk that exceeds 80% in absence of therapy.
- antiviral use is permitted in the first trimester (dell’acyclovir safe to use during pregnancy)
Classes of teratogenic exposure
PHYSICAL AGENTS :
Radiation
Hyperthermia
CHEMICAL AGENTS:
Prescription/OTC medications
Illicit substances
Noxious chemicals
MATERNAL MEDICAL CONDITIONS:
Diabetes mellitus
Hypothyroidism
Maternal PKU
INFECTIONS:
STORCH (syphilis, toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex)
Consequences of teratogenic exposure
-fetal loss
- congenital birth defect
-growth disturbance
-functional disability
How does the stage of development in a fetus affect the dgree of damage.
➢Pre- Implantation: <3 weeks post conception – significant
teratogenic exposure usually results in an early miscarriage
-If embryo is exposed to significant teratogens, it will likely result in a complete failure to develop, leading to an early miscarriage.
-If the embryo survives, it generally continues developing normally, as damaged cells can often be replaced by undifferentiated ones
without causing congenital abnormalities.
➢ Embryonic Period: 3 – 8 weeks post conception – critical
period of organogenesis – teratogenic exposure can lead to
major organ malformations
➢ Fetal Period: 9 – 38 weeks post conception – period of
growth and maturation – teratogenic exposure can lead to
morphological anomalies or functional disturbances
How dosage and duration of teratogenic exposure impact fetal devolopment
Higher dose & longer duration usually produce worse effects.
How the genetic makeup of the mother of a fetus affects the degree of damage in a fetus
➢ Maternal and fetal metabolic factors
➢ Inherent genetic susceptibility to a particular agent.
➢ Teratogenicity not constant or predictable
what is Fetal anticonvulsant syndrome
results due to a mother taking certain anti-epeleptic drugs
–Pre and postnatal growth restriction & microcephaly–Facial dysmorphism – cleft lip/palate, midface hypoplasia, long philtrum.
–Distal limb anomalies – digital & nail hypoplasia–Increased risk of neural tube defects (especially valproate).–Can have other major organ malformations
especially cardiac defects (VSD, ASD)
➢Developmental delay, intellectual disability, autism
Fetal alcohol syndrome critical period
3rd – 12th week of gestation; after 12 weeks exposure still detrimental to brain growth and development.
closed vs open neural tube defects
-In general, open defects are characterized by the external protrusion and/or exposure of neural tissue
-Closed defects have an epithelial covering (either full or partial skin thickness) without exposure of neural tissue
What is anencephaly
In anencephaly, the cranial (rostral) end of the neural tube fails to close, leading to the absence of major portions of the brain, skull, and scalp.
The cerebral hemispheres, cerebellum, and parts of the brainstem are either missing or severely underdeveloped.
The exposed brain tissue often degenerates, leaving behind a mass of disorganized neural tissue.
WHat is hydrocephalus
the accumulation of CSF inside the cerebral hemisphers
- can be due to obstruction of the normal flow of CSF or due to inability to reabsorb CSF into the venous system by the Pacchionian arachnoid granulations, or due to excessive production of CSF(common in HPE patients)
-A shunt is a thin tube implanted in the brain to drain away the excess CSF to another part of the body (often the abdominal cavity)where it can be absorbed into the bloodstream
What is holoprosencephaly
- it is the failure of the prosencephalon to divide into 2 distinct cerebral hemispheres
why do patients with HPE manifest facial abnormalities
-forebrain and midbrain arise from prechordal mesoderm, and the prominene of the face arises from the forebrain
-manifest abnormalities such as cleft lip,cleft palate, micropthalmia, flat nose, absent nasal bridge and cyclopia
-Given that patients with HPE typically have microcephaly, hydrocephalus should be suspected when macrocephaly, a normal head circumference, or an increasing head circumference is present.
what are the 4 types of HPE
-Alobar holoprosencephaly is the most severe form, and as the name implies, there is no separation of the cerebral hemispheres.
-semilobar holoprosencephaly, the cerebral hemispheres separate posteriorly, however are fused anteriorly.
-Lobar holoprosencephaly is characterized by almost complete separation of the cerebral hemispheres.
-Syntelencephaly results from failure of separation of posterior frontal and parietal lobes.
Problemos in children with HPE
-commonly have siezures/epilepsy.commonly is complex partial siezure, onset in infancy. Treated with Carbamazepine or levetiracetam.
-Motoro impairment, abnormal muscle tone and impaired coordination
- Cerebral palsy, kids benefit from physical and occupational therapy, braces or ortho surgery
-Almost all children with alobar and semilobar HPE have problems with swallowing, with the degree of impairment often correlating with the degree of motor impairment.
-oropharyngeal dysphagia
-Hypothalamic dysfunction due to lack of seperation of the hypothalamic nucleiresults in abnormal sleep–wake cycles, temperature instability, and impaired thirst mechanisms.
-Ophthalmologic problems
-craniofacial related complications
-Death is due to brainstem dysfunction
How do the primary brain vessicles form
cranial portion of the neural tube forms
-Prosencephal
-Mesencephalon
-Rhombencephalon
Secondary Brain vessicles
Prosencephalon
- Telencephlon- form telencephalic vessicles on the side- cerebral hemispheres - cacities within are the lateral ventricles
-Opening between telencephalic vessicles and telencephalic medium narrow to form intraventricular foramen of monro
- Diencephalon- Thalamus
-telencephalic medium and diancephelon cavities become 1 to form 3rd ventricle
Mesencephalon - Midbrain- cavity narrows and becomes cerebral aquaduct
Rhombencephalon
- Metencephalon - Cerebellum & Pons
- Myelencephalon - Medulla
-cavity in both forms 4th ventricle
Brain Flexures (Weeks 3, 5, and 7)
As the brain expands, it bends at key locations due to differential growth rates:
Week 3: Cephalic Flexure (In the Mesencephalon)
Week 5: Cervical Flexure (between rhombencephalon and spinal cord)
Week 7: Pontine Flexure (within the metencephalon, between pons and cerebellum)
These flexures help shape the brain into its mature structure.
Failure of the anterior nueropore to close results in
Anencephaly, anterior neuroporele failed to form the lamina terminalis, which would have induced the formation of the cranial vault and then the brain begins to degenerate
what is HPE a result of
Telencephalic vessicles did not form correctly to divide the cerebral hemispheres in 2
What could be the cause of hydrocephalus
excessive narrowing of Cerebral aquaduct or intraventricular foramena
