Craniofacial development Flashcards
What is TCS?
Treacher Collins syndrome
What causes TCS?
An abnormal formation of the first and second branchial arches during the 5th to 8th weeks of human fetal development, leading to profound facial dysmorphism.
Which gene results in TCS?
Most cases caused by loss-of-function mutations in the gene TCOF1 which encodes the protein Treacle.
Other TCS cases caused by mutations to the genes POLR1D and POLR1C which encode subunits of the enzymes RNA Polymerase I and III, important RNA synthesis.
What are the mutations of the TCOF1 gene that cause TCS?
The majority are deletions, which range in size from 1- 40 nucleotides.
however others have been found; splicing, insertions and non-sense mutations.
What is the Treacle protein responsible for?
Protein is active during embryonic development in structures that become bones and other tissues in the face.
What is the Treacle protein responsible for?
Protein is active during embryonic development in structures that become bones and other tissues in the face.
What is the effect of removal of TGF β-3 in knockout mice?
Failure of fusion of the palatal shelves - cleft palate
Key known teratogens involved in congenital malformations
ethanol, tetracycline, phenytoin sodium, lithium, methotrexate…etc
Cephalocaudal gradient
Neural features develop early, make up 50% of fetus.
Three distinct regions of embryonic origins of the skull
- Desmocranium
- Chondrocranium
- Viscerocranium
Fontanelles
The space where 2 sutures join forms a membrane-covered “soft spot” called a fontanelle. The fontanelles allow for growth of the brain and skull during an infant’s first year.
1
Coronal suture
2
Lambdoid suture
3
Sagittal suture
Describe the mechanism for remodelling of the skull
Bones move apart, theres infill mechanism. Within the skulls there’s resorption on the inside, and deposition on the outside.
Increase in intra-cranial pressure causes
Hydrocephaly
How did the Zika virus effect head size?
Causes microcephaly due to disruption with brain growth.
Craniosynostosis
Premature fusion of cranial sutures, prevents the brain expanding normally, can cause protrusion of the eyeballs.
Turricephaly
The head appears tall with a small length and width. It is due to premature closure of the coronal suture plus any other suture, like the lambdoid, or it may be used to describe the premature fusion of all sutures.
Plagiocephaly
The head is flattened on one side, causing it to look asymmetrical; the ears may be misaligned and the head looks like a parallelogram when seen from above, and sometimes the forehead and face may bulge a little on the flat side.
Trigonocephaly
The premature fusion of the metopic suture leading to deformation of anterior calvarium causing keel shaped deformity of forehead.
Cloverleaf skull
Cloverleaf deformity is a genetic disorder that children inherit from parents. Mutated genes cause sutures to fuse together prematurely (craniosynostosis). The coronal (from ear to ear) and lambdoid (across the back of the head) sutures are most commonly involved.
What happens to the chondrocranium throughout development?
Starts off as cartilage which is then replace by bone (endochondral ossification). Cartilage is interposed between large section of bone, which form the ethmoid, sphenoid and basioccipital bones.
Synchondroses of the cranial base
Primary growth centres, facilitate expansion.
The cranial base synchondrosis is composed of a combination of hyaline and fibrous cartilages. During skeletal maturation, chondrocytes proliferate, differentiate into pre-hypertrophic chondrocytes and are eventually replaced by bones at the chondro-osseous junction.
Function of displacement remodelling
Allows the face to shape forwards and outwards.
Areas of deposition and resorption.
What is the precursor of the mandible (in embryonic development)?
Meckels cartilage (osteogenesis takes place replacing this with bone).
What do Homeobox genes have a role in controlling?
Craniofacial morphogenesis
Neural crest cells
A multipotent and migratory cell population in the developing embryo that contribute to the formation of a wide range of tissues.
Make up the ectomesenchyme of first branchial arch derived from the NCC.
Examples of homeobox genes involved in the initiation, developmental position (patterning) and morphodifferentiation of tooth buds.
MSX1 and MSX2
Examples of mesenchymal growth factors
FGF, EGF, TGF and BMPs
hemifacial microsomia
Bursting of an artery (hemmorage) causes absence of ramus and body of the mandible.
Timing of palatal fusion: primary palate fusion
Week 6, day 44
Timing of palatal fusion: palatal shelves elevate
Week 7, day 54
Timing of palatal fusion: secondary palate fusion
Week 8, day 58
Embryonic development: week 2
Bilaminar embryonic disc; germ layers are created known as “embryonic cell layers”.
Ectoderm, mesoderm and endoderm
And neural crest cells.
Embryonic development: week 3
Disc has thickened to a TRIlaminar embryonic disc.
The epiblast layer is now considered the ectoderm.
Embryonic development: week 4
The disc undergoes embryonic folding, this establishes the axis, which places forming tissue types into their proper positions. Is like a “tubular embryo”.
Dynamic interactions
Happen quickly
Reciprocal interactions
One in control then other
Sequential interactions
One in control then other
Instructive tissue interactions
the ability of one tissue to determine specificpatterns of morphogenesis and differentiation that will developin an associated tissue.
Permissive (or facilitative) tissue interactions
the ability of an interacting tissue toprovide certain conditions that is necessary for its committedpartner tissue to progress to full expression of its pre-determined phenotype.
TCS: abnormalities
- Facial bone hypoplasia (mandible and zygoma)
- Ear abnormalities
- Clefts
- Dental anomalies (tooth agenesis, enamel deformities, misplacement of upper 6s)
2nd pharyngeal arch
hyoid arch
2nd pharyngeal arch: cartilage and what it forms
Cartilage: Reichert’s cartilage
Forms: Stapes, lesser horn and superior hyoid body, styloid process, stylohyoid ligament
2nd pharyngeal arch: muscles, lymphatics, nerve,
Muscles: facial expression and posterior belly of digastric
Lymphatics: thyroid gland and tonsil
Nerve: VII facial
What structures does the 3rd arch form?
Greater horn of hyoid, inferior hyoid body.
Root of the tongue
Stylopharyngeus muscle
Nerve: IX - glossopharyngeal
What does the 4th arch form?
Thyroid cartilage
Pharynx and epiglottis
Muscles: pharyngeal constrictor, soft palate
Nerve: X (vagus) - sup. laryngeal
What happens to the 5th pharyngeal arch?
Disappears rapidly
What does the 6th pharyngeal arch give rise to?
Cricoid & arytenoid cartilages
Larynx
Muscles of larynx
Nerve: vagus X - inf. laryngeal nerve
What happens to the 2nd-6th clefts?
What does the first pouch form?
What does the second pouch form?
What does the third pouch form?
What does the fourth pouch form?
