Congenital defects and their scientific basis

Question 1

What does congenital mean?

Answer 1

Present at birth- does not necessarily mean that it occurred before birth.

Question 2

What is phenotype?

Answer 2

Physical characteristics which are observable

Question 3

What is genotype?

Answer 3

Genetic makeup of an individual

Question 4

What are the types of abnormal morphogenesis?

Answer 4

Deviation of body structure from the norm
->Disturbance
->Disruption
->Malformation

Question 5

What is a deformation?

Answer 5

Late stage abnormality during normal development due to later stage mechanical forces which reduce foetal movement.

Question 6

What is disruption?

Answer 6

Disruption in normal morphogenesis because of early influence from external factors that are destructive such as teratogens or infections.

Question 7

What is malformation?

Answer 7

Primary disturbance of embryogenesis which is established as abnormal due to genetics and/or environment so no normal development occurs.

Question 8

How are congenital abnormalities classified?

Answer 8

Based on the aetiology and the timing of the issue.
-> Is it disruption/disturbance/malformation/Sequential issue?

Question 9

What is a sequential anomaly?

Answer 9

Primary error with a cascade of events and consequences.

Question 10

What is the cause of a majority of congenital defects?

Answer 10

Majority of congenital defects are unknown
Of the known, majority are polygenic, the interaction of multiple genes. Lesser are single gene and chromosomal defects

Question 11

What is a primary anomaly?

Answer 11

Abnormality in morphogenesis due to mutation of a single gene, chromosome or polygenic issue.

Question 12

What is a secondary anomaly?

Answer 12

Abnormality in morphogenesis due to external factors such as a teratogen or an infection

Question 13

What are the teratogens?

Answer 13

->Infections such as:
Toxoplasmosis, Rubella, Cytomegalovirus, Herpes, Varicella, Parvovirus

->Drugs/medications such as Vitamin A, alcohol and medication
->Maternal diabetes mellitus

Question 14

Why is Vitamin A harmful in pregnancy?

Answer 14

Excess Vitamin A, such as in retinoids can lead to malformations such as spina bifida in the foetus, cleft palate and deformities in the limbs.

Question 15

What are the early effects of teratogens in embryo at 2-4 weeks gestation?

Answer 15

Abnormality affecting a single cell or gene will present in many different body areas- this is a polytropic defect

Question 16

What are the late effects of teratogens in embryo at 4-8 weeks gestation?

Answer 16

Localised defect which affects only a sub-population of cells- this is a monotropic defect.

Question 17

What are the effects of teratogens in the foetal stage?

Answer 17

Affects organogenesis of specific tissues and organs.

Question 18

What affects teratogenic susceptibility in pregnancy?

Answer 18

Stage of development- embryonic stage has the greatest susceptibility due to cells and systems not being formed/very immature, and this wide-range susceptibility is very low in foetal stage for all tissues except the CNS. CNS remains susceptible to teratogens throughout pregnancy.

Question 19

What stage of pregnancy has the most adverse outcomes of teratogens?

Answer 19

Pre-embryonic stage from fertilisation to 2nd week which is driven by zygote replication.

Question 20

What are examples of congenital abnormalities caused by deformation?

Answer 20

Abnormality of body due to mechanical force:
-> Talipes
-> Congenital hip deformation

Question 21

What is talipes?

Answer 21

Achilles tendon is shorter that causes the feet to turn inwards, due to intrauterine growth restriction where the baby was too large or low levels of amniotic fluid. This is a type of deformity.

Question 22

What is congenital hip deformation?

Answer 22

Congeital dislocation of ball and socket joint because of low amniotic fluid or vaginal birth in the breech position. This is a type of deformity.

Question 23

What are the examples of congenital abnormalities caused by disruption?

Answer 23

External destructive factors interrupt normal morphogenesis
->Amniotic bands
->Poland anomaly

Question 24

What is an amniotic band?

Answer 24

Amniotic membrane is torn or ruptured and wraps around the digit/limb of the foetus, resulting in constricted blood supply and loss of the affected body part. This is a type of disruption.

Question 25

What is a Poland anomaly?

Answer 25

Interruption of the subclavian artery which leads to unilateral underdevelopment/absence of the pectoralis muscle. This is a type of disruption.

Question 26

What are the examples of congenital abnormalities caused by seuqential issues?

Answer 26

Primary error with a cascade of events and consequences.
-> Potter Sequence
->Pierre-Robin sequence

Question 27

What is a Potter Sequence?

Answer 27

Condition where there is renal agenesis that causes low amniotic fluid. This increases in utero pressure and causes foetal compression and reduces foetal urine excretion.

Low amniotic fluid means less fills the lungs during development, leading to pulmonary hypoplasia.

Question 28

What is a Pierre-Robin sequence?

Answer 28

Mandibular hypoplasia, meaning the tongue is too large for the mouth that leads to upper airway obstruction and prevention of secondary palates developing.

Question 29

What is Di-George syndrome?

Answer 29

Genetic condition caused by the deletion of a region in chromosome 22 for the TBX-1 developmental gene. This is important for the development of pharyngeal pouches 3 and 4 for the thyroid and parathyroid gland and thymus.

Question 30

What does the 3rd pharyngeal pouch give rise to?

Answer 30

Thymus and inferior parathyroid gland.

Question 31

What does the 4th pharyngeal pouch give rise to?

Answer 31

Superior parathyroid.

Question 32

What is the presentation of Di-George syndrome?

Answer 32

Underdeveloped thymus causes hormonal disturbances due to hypoparathyroidism, feeding problems, immunological disturbances because of less T cell production and speech delays.

CATCH 22:
Cardiac abnormality
Abnormal face
Thymus undervelopment
Cleft palate
Hypocalcaiemia/Hypoparathyroidism
22: deletion of chromosome 22

Question 33

What is Charge syndrome?

Answer 33

Multi-organ system abnormality caused by a heterozygous mutation in the CH7 gene (chromodomain helicase DNA-binding protein 7) which regulates chromatin remodelling and essential for formation of multipotent neural crest cells.

Question 34

What are neural crest cells?

Answer 34

Involved in embryological development of the nervous system and give rise to the PNS (cranial nerves) facial skeleton and the smooth muscle, cartilage and connective tissue.

Question 35

What is the precursor to the CNS?

Answer 35

Neural tube.

Question 36

What is the presentation of CHARGE syndrome?

Answer 36

Absence of CHD7 gene leads to issues with the development of the head and neck, heart and adrenal medulla

C- coloboma (defect in iris)
H- Heart defect
A- Atresia of Choana which narrows nasal airways
R- Retardation of growth and development
G- Genital hypoplasia
E- Ear defect

Question 37

What is spina bifida?

Answer 37

Defect in the closure of the caudal neuropore, commonly occurring in the lumbosacral region. This creates structural abnormalities in the brain which prevents proper drainage of the CSF, causing hydrocephales.

Question 38

Why does spina bifida occur?

Answer 38

Occurs due to a combination of genetic predisposition and environmental factors such as deficiency in folic acid, worsened by anti-epileptic drugs.

It typically occurs in the lumbosacral region.

Question 39

What are the types of spina bifida?

Answer 39

Meningoceles: Gap in the vertebrae that allows a sac of fluid contaninig the mater and CSF to be extruded.

Myelomeningoceles: Gap in the vertebrae that allows a sac of CSF containing the meninges (mater) and neural/spinal elements to be extruded, leading to nerve underdevelopment.

Question 40

What is hydrocephales?

Answer 40

Abnormal build of up cerebrospinal fluid in the brain ventricles

Question 41

What is the consequence of alcohol intake in pregnancy?

Answer 41

Neural crest cells are sensitive to alcohol and results in lower migration. This leads to improper formation of the facial skeleton because it derives from neural crest cells of the pharyngeal arches. Causes short nose, flat midface, small eye opening and low nasal bridge.

Question 42

What is congenital rubella syndrome?

Answer 42

Maternal infection with rubella virus which causes necrosis of chorionic epithelia and inhibits mitosis and development of precursor cells. Leads to microencephaly (incomplete brain development), cloudy patches in the eye called cataracts and patent ductus arteriosus

Question 43

What are the impacts of congenital abnormalities?

Answer 43

It accounts for 3% of neonatal deaths worldwide. Causes perinatal and neonatal death and disability, emotional and financial costs and there are historical beliefs of causation.

Question 44

What is the most common cause of neonatal death?

Answer 44

Pre-term birth complications or intrapartum complications.

Question 45

What is the most common cause of death in children?

Answer 45

Diarrhoea and pneumonia.

Question 46

What form of screening for conditions can be carried out before conception?

Answer 46

Genetic counselling to investigate risk of genetic disorders.

Question 47

What are the screenings in the first trimester?

Answer 47

Triple test for Down’s syndrome, Patau’s syndrome and Edward’s syndrome.
Nuchal fold assessment

Question 48

What is the Nuchal fold assessment?

Answer 48

Fold at the back of the foetal neck used to identify trisomy 21 in Down’s syndrome

Question 49

What are the screenings in the second trimester?

Answer 49

At week 20, there is an anomaly scan for the structures of the foetus and the placenta.

Question 50

How is a diagnosis made?

Answer 50

Physical examination, family history and diagnostic tests with radiology and genetic analysis.

Question 51

What is the impact of congenital rubella infection?

Answer 51

Affects the development of the special sense organs, causing hearing impairments and cataract formation. It affects the heart by causing patent ductus arteriosus.