Confenital Malformations 1 Flashcards
What is holoprocencephaly mainly caused by (eg Cyclopia 1 eye)
Chr abnormalities
What are the 5 most common types of malformations
Kidney disease
Craniofacial eg cleft palate
Multisystem eg culiopathies
Chd
Ntd
When do these anomalies occur
Embryogenesis 8 weeks first of pregnancy
Why
It’s when organogenesis is and most susceptible to teratogens (factors)
Why do we use developmental biology
Unethical to study embryos
Also genes for development are preserved eg pax6 for eye development
What are the 4 patterns of anomalies
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
Give example of an isolated anomaly which is complex genetic polygenic
Isolated cleft palate
(Can also be part of a syndrome or with other cleft eg lip cleft)
What is one of the causal genes found and why is it associated with ankyloglossia (tongue tie)
Tbx22
High exp in orifacial cavity
Give an example of a syndrome with known gene cause
Holt oram syndrome
Defects in upper limbs and heart
What is the gene inherited autosomal dominant
Tbx5 (expressed in heart and forelimbs)
Give an example of a sequential anomaly
Pierre robin sequence
What is the primary defect causing which other symptoms
Micrognathia, deformed growth of lower jaw
This causes tongue displacement so palate can’t open and airway blockage
Is it inherited
No, it is many de novo mutations eg sox9
Which inheritance patterns to congenital anomalies take
Single gene - eg holt oram
Polygenic - eg cleft palate
Chr abnormalities - digeorge
Whcih anomaly does zika cause
Microcephaly
Which chr abnormality is deletion of chr and 22q 11.2
Di George
What is one of the genes known lost in digeorge causing anomalies
Tbx1
Has many features like thymus hypoplasia and parathyroid hypoplasia. How is this possible
All derive from pharyngeal pouches where tbx1 is highly expressed usually
Which other syndrome is caused by a single gene mutation
Ulnar mammary syndrome (tbx3)
Why are these tbx genes important
Tf for development genes
Which gene family is known to cause congenital anomalies and how
Hox genes
Tf which pattern the body axis
Can deform limb and digit and body axis development if mutated
What is the dna bd called
Homeobox
Is Ntd multi factorial ie both genes and environment
Yes
What is the neural tube
Precursor for brain and spinal cord
In Ntd it doesn’t close properly
Give 3 types
Anencephaly - no closure in cranial area
Craniorachischisis - no closure of entire neural tube
Spina bifida - open at the lower spine
Give some environmental factors for Ntd
Maternal diabetes , folate levels , obesity
What is the non canonical wnt signalling pathway which is associated with Ntd
Planar cell polarity
Gene variation = Ntd
What is the planar cell polarity signalling for
Convergence extension/ regulating cell polarity (where tissue of embryo is arranged on the body axis)
Disruption = neural tube too wide
Is it just a mono gene effect
No many genes in pathway act together (see fr)
Which vitamin pathway which transports it from mother to embryo is linked to ntd
Folate pathway (receptors and transporters mutations found)
What treatment can now be given for ntd
Folate replacement
Give example of movement cilioparhies
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
How are cilia used for sending
Eg photoreceptors with modified cilia. If defects can cause progressive retinitis pigmentosa
Why are cilia important in signalling pathways like wnt and shh for patterning
Many receptors hide under the cilia
Give an example of how signalling disruption causes anomalies through ciliopathy
Craniofacial movement of facial features to the midline of face is disrupted by shh signaling being disrupted
Give another example of how left right patterning ciliopathies cause congenital defects
Sinus invertus where organs are misplaced
