013 craniofacial development and disease Flashcards
what are the 3 germ layers in an embryo?
- endoderm
- mesoderm
- ectoderm
what is the neural crest?
- “4th germ layer”
- formed post gastrulation
- ectoderm derived
- originates at the neural fold during neurulation
- forms the PNS, as well as facial cartilage and connective tissue, adrenal medulla, odontocytes and melanocytes
what are the 3 parts of a baby’s skull?
- viscerocranium (face)
- chondrocranium (skull base /back)
- neurocranium (skull vault /top)
describe the neurocranium
- part of the skull that protects and contains the majority of the brain
- intramembranous bone (flat)
- anterior = neural crest, posterior = mesoderm
- joined by sutures
- includes frontal, parietal and occipital bones
describe the chondrocranium
- part of the skull of the base/back
- includes occipital, sphenoid and ethmoid bones
describe the viscerocranium
- bones and cartilages of the face and neck
- includes maxilla, mandible, zygomatic and ossicles of inner ear
what are the 2 types of bone formation in the skull?
- endochondral ossification = cartilage model first forms and then replaced by bone = chondrocranium
- intramembranous ossification = bone formed directly without cartilage precursor = neurocranium and viscerocranium
describe endochondral ossification in the skull
- chondrocranium
- from mesodermal mesenchyme
- SOX9 gene involved
- chondrocytes form a cartilage template
- osteoblasts then use the template to guide bone growth and vascularization
- primary ossification centre in the middle then epiphyseal growth plates and then secondary ossification centres at the end of the bones
- articular cartilage remains on the end of bones
describe intramembranous ossification in the skull
- neurocranium and viscerocranium
- from neural crest-derived mesenchyme
- RUNX2 gene involved
- osteoblasts derived from the neural crest mesenchyme form and deposit bone between 2 membranes/layers of osteoblasts
- sutures between bones instead of joints
what are the first parts of the viscerocranium that forms?
- frontonasal prominence (FNP), maxillary prominence, mandibular prominence and hyoid arch
- formed from the first pharyngeal arch (PA1)
- paraxial mesoderm and neural crest mesenchyme
- eventually these all fuse together as one facial structure
- at about 3 weeks
what are the pharyngeal arches?
- 5 bilateral arches 1,2,3,4,6
- form after 4 weeks of development
- contain all 4 germ layers (ectoderm, mesoderm, endoderm, neural crest)
- form different structure of the upper body (mainly head and neck)
why is there no PA5?
PA5 either never forms or quickly regresses as other animals that have PA5 develop structures humans do not have
what does each pharyngeal arch contain?
- rod of cartilage (from neural crest cells)
- artery and skeletal muscle (from mesoderm)
- a single cranial nerve
what are the pharyngeal cartilages of the maxillary prominences called?
palatopterygoquadrate cartilages
- PA1 = Meckel’s cartilage
- PA2 = Reichert’s cartilage
what cartilages do the pharyngeal arches form?
- PA1 = alisphenoid (orbit), Meckel’s cartilage (jaw), malleus and incus (ossicles)
- PA2 = stapes (ossicle), styloid process, stylohyoid ligament, lesser cornu of hyoid
- PA3 = body of hyoid, greater cornu of hyoid
- PA4 = thyroid and cricoid cartilage
what muscles do the pharyngeal arches form?
- facial muscles = PA1,2 = formed by paraxial mesoderm and occipital somites
PA1 = mylohyoid, temporalis, masseter
PA2 = frontalis, orbicularis oculi and oris, auricularis, buccinator, digastric
PA3 = stylohyoid, stylopharyngeus
PA4 = cricothyroid, middle and inferior constrictor pharynx
PA6 = intrinsic larynx muscles
what nerves innervate the different pharyngeal arches?
- PA1 = trigeminal (V)
- PA2 = facial (VII)
- PA3 = glossopharyngeal (IX)
- PA4 = vagus (X)
What cranial nerve innervates PA1?
trigeminal (V)
what cranial nerve innervates PA2?
facial (VII)
what cranial nerve innervates PA3?
glossopharyngeal (IX)
what cranial nerve innervates PA4?
vagus (X)
what is the initial structure of the pharyngeal arteries?
- they initially form a ‘basket’ structure similar to gill system of fish
- the heart pumps blood through these arteries into the paired dorsal aortae
- week 5
what is the arrangement of pharyngeal arteries by week 8?
- the arteries remodel to form definitive arteries of the head, neck and upper thorax
- PA1 = brachiocephalic, maxillary, external and left common carotid
- PA2 = internal carotid, stapedial
- PA4 = left pulmonary
- PA6 = left subclavian
what are pharyngeal pouches?
- pouches that form on the endodermal side between the pharyngeal arches
- go on to form various structures
what does the first pharyngeal pouch form?
- middle ear and tympanic membrane
what does the second pharyngeal pouch form?
- middle ear and palatine tonsils
what does the third pharyngeal pouch form?
- inferior parathyroid glands, thymus
what does the fourth pharyngeal pouch form?
-superior parathyroid glands, ultimobranchial body and musculature/cartilage of the larynx
what are pharyngeal clefts?
- grooves/clefts that seperate the pharyngeal arches on the ectodermal side
what do the pharyngeal clefts form?
- the 1st cleft forms the external auditory tube
- the remaining 2-4 clefts form temporary cervical sinuses and are then obliterated by an outgrowth of the 2nd pharyngeal arch
what is the clinical relevance of pharyngeal clefts?
- if clefts 2-4 are not obliterated by 2nd pharyngeal arch then they can persist into adulthood and form branchial cysts (usually surgically removed)
what are the main fuses in the face structures during development (week 5-7)?
- nasal plaxodes of the frontonasal (fnp) invaginate to form nasal pits and lateral and medial nasal processes
- medial nasal processes fuse at midline to form intermaxillary process
- maxillary prominences fuse with nasal processes and form upper jaw and cheeks (maxillary bone)
- mandibular prominences fuse across midline to form lower jaw and chin (mandibular bone)
- the hard palate also fuses across the midline here
how common are cleft lip and/or palate?
1/700 babies are born with either
- more common in males
30% are syndromic
what is cleft lip caused by?
- failure of maxillary prominences to fuse with intermaxillary process
- cause unknown, both genetic and environmental
- maybe due to smoking
- often part of a syndrome affecting structure of head
-90% are unilateral - usually corrected in first 8 months
describe the development of the palate
- primary palate (pp) is formed by an extension intermaxillary process
- secondary palate forms from palatine shelves (ps) that grow medially from maxillary prominences (mp)
- at the same time, growth of nasal septum (ns) separates left and right nasal chambers (NC)
- initially palatine shelves grow beneath the tongue (t) but soon move upwards to meet at midline above the tongue where they fuse with the nasal septum
- front 1/2 of palate undergoes endochondral ossification forming the hard palate
why is cleft palate/lip a functional issue for babies?
- affects feeding, speech, hearing, teeth development and psychological development
- easily fixed cosmetically but needs lots of specialists to repair muscle and dentistry underneath
what is cleft palate caused by?
- failure of palatial shelves to fuse during 7-10th week of development
- often associated with other congenital head syndromes
what is submucous cleft palate?
- when you have an intact mucousal membrane superficial to the hard palate which has failed to fuse
- so there is a cleft/notch underneath the mucosa with no bone/muscle
- due to Tbx22 mutation?
why are craniofacial sutures important during development?
they allow the head to deform during birth and expand during childhood as the brain grows
- large membrane covered fontanelles are found where several bones meet (soft/delicate areas)
what are the 5 sutures on a child’s growing skull?
- sagittal, coronal, metopic, lamdoid, squamosal
what are the 4 fontanelles on a baby’s brain?
- anterior, sphenoidal, mastoid, posterior
what is craniosynostosis?
- premature closure of 1 or more sutures in the skull (most often saggital)
- affects 1/2,500 newborns
- occurs when the osteoblasts in the sutures differentiate prematurely
- can increase pressure on the brain (no room to grow) = intellectual disabilities
- can be surgically fixed soon after birth
what is the cause of craniosynostosis
- non-syndromic = majority (70%) = no genetic link, could be due to in utero constriction, fixed with single surgery
- syndromic (30%) = Crouzon, Pfeiffer,, Apert and Muenke syndromes can also cause midfacial hypoplasia, cleft palate, limb defects and hearing loss = often requires repeat surgeries as suture re-fusion can occur
- syndromic due to mutations in FGF receptors
how are FGF receptors involved in craniosynostosis?
- most syndromes causing craniosynostosis are caused by mutations in the genes for Fibroblast growth factor receptors (FGF)
e.g. FGFR1,2,3 = regulate RunX2 = controls osteoblasts
also genes that regulate FGF pathway have been linked
e.g. TWIST1, ERF, TCF12 - mutation causes receptor to increase activity which drives premature bone differentiation = ossification of suture
