Confenital Malformations 1

Question 1

What is holoprocencephaly mainly caused by (eg Cyclopia 1 eye)

Answer 1

Chr abnormalities

Question 2

What are the 5 most common types of malformations

Answer 2

Kidney disease
Craniofacial eg cleft palate
Multisystem eg culiopathies
Chd
Ntd

Question 3

When do these anomalies occur

Answer 3

Embryogenesis 8 weeks first of pregnancy

Question 4

Why

Answer 4

It’s when organogenesis is and most susceptible to teratogens (factors)

Question 5

Why do we use developmental biology

Answer 5

Unethical to study embryos

Also genes for development are preserved eg pax6 for eye development

Question 6

What are the 4 patterns of anomalies

Answer 6

Isolated - affecting 1 structure/organ

Syndromes - multi organ with known cause

Sequential - multi structural due to interconnected development

Associations - multiple organs affected no known cause

Question 7

Give example of an isolated anomaly which is complex genetic polygenic

Answer 7

Isolated cleft palate

(Can also be part of a syndrome or with other cleft eg lip cleft)

Question 8

What is one of the causal genes found and why is it associated with ankyloglossia (tongue tie)

Answer 8

Tbx22

High exp in orifacial cavity

Question 9

Give an example of a syndrome with known gene cause

Answer 9

Holt oram syndrome

Defects in upper limbs and heart

Question 10

What is the gene inherited autosomal dominant

Answer 10

Tbx5 (expressed in heart and forelimbs)

Question 11

Give an example of a sequential anomaly

Answer 11

Pierre robin sequence

Question 12

What is the primary defect causing which other symptoms

Answer 12

Micrognathia, deformed growth of lower jaw

This causes tongue displacement so palate can’t open and airway blockage

Question 13

Is it inherited

Answer 13

No, it is many de novo mutations eg sox9

Question 14

Which inheritance patterns to congenital anomalies take

Answer 14

Single gene - eg holt oram

Polygenic - eg cleft palate

Chr abnormalities - digeorge

Question 15

Whcih anomaly does zika cause

Answer 15

Microcephaly

Question 16

Which chr abnormality is deletion of chr and 22q 11.2

Answer 16

Di George

Question 17

What is one of the genes known lost in digeorge causing anomalies

Answer 17

Tbx1

Question 18

Has many features like thymus hypoplasia and parathyroid hypoplasia. How is this possible

Answer 18

All derive from pharyngeal pouches where tbx1 is highly expressed usually

Question 19

Which other syndrome is caused by a single gene mutation

Answer 19

Ulnar mammary syndrome (tbx3)

Question 20

Why are these tbx genes important

Answer 20

Tf for development genes

Question 21

Which gene family is known to cause congenital anomalies and how

Answer 21

Hox genes

Tf which pattern the body axis
Can deform limb and digit and body axis development if mutated

Question 22

What is the dna bd called

Answer 22

Homeobox

Question 23

Is Ntd multi factorial ie both genes and environment

Answer 23

Yes

Question 24

What is the neural tube

Answer 24

Precursor for brain and spinal cord

In Ntd it doesn’t close properly

Question 25

Give 3 types

Answer 25

Anencephaly - no closure in cranial area Craniorachischisis - no closure of entire neural tube Spina bifida - open at the lower spine

Question 26

Give some environmental factors for Ntd

Answer 26

Maternal diabetes , folate levels , obesity

Question 27

What is the non canonical wnt signalling pathway which is associated with Ntd

Answer 27

Planar cell polarity Gene variation = Ntd

Question 28

What is the planar cell polarity signalling for

Answer 28

Convergence extension/ regulating cell polarity (where tissue of embryo is arranged on the body axis) Disruption = neural tube too wide

Question 29

Is it just a mono gene effect

Answer 29

No many genes in pathway act together (see fr)

Question 30

Which vitamin pathway which transports it from mother to embryo is linked to ntd

Answer 30

Folate pathway (receptors and transporters mutations found)

Question 31

What treatment can now be given for ntd

Answer 31

Folate replacement

Question 32

Give example of movement cilioparhies

Answer 32

Sperm tail is a modified cilium (flagella) If mutations it causes male infertility Also need movement of liquids eg at the node or mucociliatary escalator = bronchitis

Question 33

How are cilia used for sending

Answer 33

Eg photoreceptors with modified cilia. If defects can cause progressive retinitis pigmentosa

Question 34

Why are cilia important in signalling pathways like wnt and shh for patterning

Answer 34

Many receptors hide under the cilia

Question 35

Give an example of how signalling disruption causes anomalies through ciliopathy

Answer 35

Craniofacial movement of facial features to the midline of face is disrupted by shh signaling being disrupted

Question 36

Give another example of how left right patterning ciliopathies cause congenital defects

Answer 36

Sinus invertus where organs are misplaced