Congenital Abnormalities And Their Scientific Basic

Question 1

Meaning of congenital

Answer 1

Present at birth, does not denote aetiology

Question 2

What is an anomaly

Answer 2

Structural deviation from the norm

Question 3

What are congenital abnormalities

Answer 3

Occur when normal embryonic development is disrupted

Question 4

What is a deformation

Answer 4

Late changes in previously normal structures (mechanical effect)

Question 5

What is disruption

Answer 5

Secondary disturbance due to early influence of external factors

Question 6

What is malformation

Answer 6

Primary disturbance of embryogenesis

Question 7

How are congenital anomalies classified

Answer 7

By cause
Timing ( explains problem)

Question 8

Difference between disruption and deformation

Answer 8

Disruption: starts out okay then goes wrong

Deformation = was okay but then is squashed

Question 9

What is sequence:

Answer 9

One primary error with a cascade of events and consequences

Question 10

What can aetiology be grouped into

Answer 10

Single gene defects = 20%

Chromosomal = 10%

Polygenic = 25-30%

Teratogenic = 6-9%

Unknown = 35-40%

Question 11

What is the difference between a primary and secondary anomaly

Answer 11

Primary is at the genetic level and maybe due to chromosomal, single gene or polygenic factors

Whilst a secondary anomaly is due to an external factor such as a teratogen

Question 12

Examples of congenital infections that are teratogenous

Answer 12

Toxoplasmosis

Others = varicella, parvovirus and syphilis

Rubella

Cytomegalovirus

HIV

Question 13

Examples of environmental pollutants and drugs that are teratogenic

Answer 13

Vitamin A

Pesticides

Medication

Alcohol

Question 14

Examples of maternal metabolic diseases that maybe teratogenic

Answer 14

DM

Question 15

What else is teratogenic

Answer 15

Radiation exposure

Question 16

What are the early effects (classification by timing)

Answer 16

In 2-4 weeks

Polytropic defects = scattered pattern with significant effect on cell populations

Question 17

What are the late effects

Answer 17

4-8 weeks of gestation

Monotropic effects - localised defects due to formation of sub-populations of cells

Question 18

Effects in the foetal period -

Answer 18

Greater than 9 weeks

Organogenesis so specific organs or systems are affected

Question 19

Examples of deformities

Answer 19

Talipes - club foot

Congenital hip deformation

Question 20

What is talipes

Answer 20

Example of a deformity in which the feet have been squashed during development and have a clubbed appearance

Question 21

What is congenital hip deformation

Answer 21

Where morphology and alignment of the hip/hips have been squashed during development

Question 22

Examples of disruption

Answer 22

Amniotic bands (strips of amniotic membrane)

Poland anomaly

Question 23

What are amniotic bands

Answer 23

Form of disruptive anomaly in which strips of the amniotic membrane wrap around limbs or digits and cause constriction of the blood supply. Can cause ischaemia and loss of digit or limb

Question 24

What is the Poland anomaly

Answer 24

A form of disruptive anomaly in which there is unilateral absence of pectoralis major muscle due to the interruption of the subclavian artery. Loss of supply and nutrients occurs

Question 25

Examples of sequence anomalies

Answer 25

Potter sequence Pierre robin sequence

Question 26

What is potter sequence

Answer 26

True kidneys do not develop properly (renal agenesis) so no foetal urine production which causes oligohydroamnios The lack of amniotic fluid causes mechanical squashing Results in baby with limb deformities, respiratory failure due to pulmonary hypoplasia. Face has low set ears, slanted eyes and a beaked nose

Question 27

What is Pierre robin sequence

Answer 27

Begins with mandibular hyperplasia which does not allow tongue to drop which then affects the development of the palate

Question 28

In what ways can a single gene be impacted

Answer 28

Mutation Deletion

Question 29

In which ways can chromosomes be impacted

Answer 29

Translocation Microdeletions Duplications as seen in downs, Edward’s and Pataus

Question 30

What is di George syndrome

Answer 30

Deletion of a section of the 22nd chromosome Specifically 22q11.2 Contains an important gene for development called TBX-1

Question 31

What gene is implicated in di George syndrome

Answer 31

TBX-1

Question 32

What are the range of anomalies experienced in di George syndrome

Answer 32

Hormonal and immunological disturbances due to development of thymus and parathyroid glands being affected Speech delay and delayed development in infancy Cardiac anomalies Hypocalcemia?

Question 33

The embryonic development of which structures is affected in Di George syndrome

Answer 33

Failure to develop 3 and 4th pharyngeal pouches which gives rise to thymus and parathyroid glands

Question 34

What is charge syndrome

Answer 34

A heterozygous mutation in CHD7 gene CHD7 = chromodomain helicase DNA binding domain, ATP dependent chromatin remodeller

Question 35

Why is expression of CHD7 gene vital

Answer 35

Expression allows for the production of multi potent neural crest cells So is important in the development of the heart, the head + neck and the adrenal medulla

Question 36

What does CHARGE stand for

Answer 36

C = coloboma = missing piece of tissue that makes up your eye H = heart defects A = choanol atresia (choanae are blocked by bone or tissue) R = growth and developmental retardation G = genital hypoplasia E = ear defects

Question 37

What do the neural crest cells give rise to

Answer 37

Sensory ganglia of the cranial nerves Ganglia of the ANS Spinal ganglia Glial cells Schwann cells Pigment cells - melanocytes Adrenomedullary cells Calcitonin producing cells

Question 38

Spina bifida is resulted when failure to close which Neuropore occurs

Answer 38

Caudal neuropore

Question 39

Spina bifida defect can occur anywhere along the length of the neural tube but where is the most common location

Answer 39

Lumbosacral region

Question 40

What also accompanies spina bifida

Answer 40

Hydrocephalus And sometimes neurological deficits

Question 41

How is development of spina bifida multi-factorial

Answer 41

Genetic Environmental Maternal nutritional status

Question 42

What is the incidence of Di George syndrome

Answer 42

1 in every 3000 births

Question 43

Incidence of FAS

Answer 43

1/100 births

Question 44

The facial skeleton is derived from what

Answer 44

Neural crest cells populating the pharyngeal arches The migration of neural crest cells is extremely sensitive to alcohol

Question 45

What is congenital rubella syndrome

Answer 45

Viral infections affects development of organs of special senses, heart Microcephaly PDA patent ductus arteriosus Cataracts

Question 46

Congenital anomalies affect what % of liveborn infants

Answer 46

3% Causing perinatal and neonatal death and disability

Question 47

What is the lifelong impact to child and family y

Answer 47

20-30% admissions to tertiary care. Emotional and physical wellbeing impacted Financial cost Historical beliefs still present in some cultures where it is believed that cause is supernatural/ associated with witchcraft

Question 48

What is the number one cause of neonatal deaths worldwide

Answer 48

Pre term birth complications 34% Congenital anomalies account for 9%

Question 49

What types of screening are available

Answer 49

Pre conception = genetic counselling Antenatal screening = in first and second trimester Newborn screening examination

Question 50

What antenatal screening is available in first trimester

Answer 50

Triple test (looks at levels of alpha fetoprotein, hCG and estriol Nucal fold (increased thickness is associated with anomalies)

Question 51

What antenatal screening cna be carried out in the second trimester

Answer 51

Anomaly scan at 20 weeks