The document outlines craniofacial development from embryology through birth. It discusses how facial tissues originate from ectoderm and neural crest cells. It describes 5 stages of craniofacial development from germ layer formation to organ system formation. Common craniofacial disorders are explained such as fetal alcohol syndrome, cleft lip/palate, and craniosynostosis syndromes. Growth and development of specific structures like the nose, palate, and mandible are detailed. Growth mechanisms and sites are compared for cranial vault, cranial base, nasomaxillary complex, and mandible.

1. Craniofacial Development Outline for Test #1
Craniofacial Embryology
 Most facial tissues originate for ectoderm
 In particular, from neural crest cells that migrate downward beside the neural tube and laterally
under the surface ectoderm.
 Stages in craniofacial development:
o 1st -germ layer formation and initial organization of craniofacial structure
 Day 17
 Fetal alcohol syndrome
 Deficiencies of the midline tissue of the neural plate very early in embryonic
development.
 Caused by exposure to high levels of ethanol
 Implicated in many cases of maxillary and midface deficiency.
 Diagnosed by varying degrees of discriminating clinical features: short palpebral
fissures, flat midface, short nose, indistinct philtrum, and thin upper lip.
Associated features: low nasal bridge, epicathnal folds, minor ear anomalies,
micrognathia.
o 2nd -neural tube- formation and initial formation of the oropharynx
 Day 18-23
 Ancephaly
o 3rd- origins, migrations, and interactions of cell populations
 Day 19-28
 Mandibulofacial dystomia
 Treacher Collin’s syndrome
 Results from altered neural crest development
 Both maxilla and mandible are underdeveloped bilaterally as a result of
generalized lack of mesenychymal tissue.
 Arises because of excessive cell death in the trigeminal ganglion, which
secondarily affects the neural crest cells.
 Neural crest cells migration can be affected by drugs:
o Thalidomide- morning sickness
o Accutane- acne
 Hemifacial microsomia
 Unilateral and asymmetric problem
 Lack of tissue seen on the affected side of the face
 External ear deformity and both the ramus and associated soft tissues are
deficient or missing.
 Arises primarily form early loss of neural crest cells.
 Defects in great vessels (example: teratology of Fallot) are commonly affected.
o Caused by a lack of neural crest cells migrating to lower regions.
 Treatment: bionator with open on the affected side and closed on the normal
side. Can also implant rib cartilage in the condyle area.
 Limb abnormalities
o 4th- Formation of organ systems
 Day 28-55
 Primary palate forms day 28-38: Cleft lip and or palate
 Secondary palate forms day 42-55: Other facial clefts
 Cleft lip and palate
 Most common congenital defect involving the face and jaws.

2.  Occurs when fusion of the various facial processes fail to occur
 CL: median and lateral nasal processes and maxillary prominence (6th week)
o Notch in the alveolar process
o Alveolar ridge containing central and lateral incisors is often involved.
o 60% have a cleft palate
o Etiologic factor: cigarette smoking
 CP: secondary palatal shelves
o Problem that arises after lip closure is complete (2 weeks later, 8th week)
o Incomplete fusion of secondary palate
o Minor expression: notch on the posterior extent (bifid uvula)
 Cleft lip
 Cleft palate
o 5th- final differentiation of tissues
 Day 50+
 Achondroplasia
 Synostosis Syndromes- Crouzan’s, Aperts
 Crouzan’s syndrome
 A synostosis syndrome that results from early closure of sutures between cranial
and facial bones.
 Underdevelopment of the midface and eyes that seem to bulge from their
sockets.
 It is due to prenatal fushion of the superior and posterior sutures of the maxilla,
along the wall of the orbit, and often the cranial vault.
 Late fetal development and birth
 During the last 3 months of intrauterine life, continued rapid growth results in
tripling of body mass.
 Development of all primary teeth and the permanent 1st molars starts well
before birth.
 During birth the head is increased in length and decreased in width to facilitate
passage through the birth canal.
 The lack of lower jaw growth prenatally also facilitates birth.
 Postnatally, the mandible grows more than another other facial structures and
catches up.
 For a short period, growth ceases and there is a small decrease in weight during
the first 7-10 days of life.
 This cessation can disrupt skeletal tissue formation leading to noticeable lines
(neonatal lines) across both both bones and teeth that are forming at that time.
 Growth disturbances lasting 1-2 weeks or more caused by either birth or febrile
illness can also result in visible records on the enamel.
 Initiation of the oral cavity occurs in the 3rd prenatal week as a pit or invagination (stomodeum) of the
tissue underlying the forebrain
 This pit will later develop into the oral cavity, and the tissue surrounding it develops into 5 or 6 pairs
of bars named “pharyngeal arches,” which later from the lower part of the face and neck.
 Facial development
o The face develops during the 5th and 7th prenatal week from 4 primordia that surround a
central depression known as central pits.
o Frontal process
 Single process located cranially
 Gives rise to upper face
o 2 Maxillary processes

3.  Arise from 1st pharyngeal arch
 Start laterally and move medially
o Mandibular process
 Arise from 1st pharyngeal arch
 Initially appears partially divided, but then soon merges at the midline to form a single
structure
 Gives rise to the mandible, lower part of the face and body of the tongue.
o By the end of the 4th week
 Nasal placodes- develop bilaterally at the lower margin of the frontal process.
 These placodes quickly become recessed as the tissue around them grows, causing
them to appear depressed.
 The depressions= nasal pits.
 The area where nasal pits appear is called= frontonasal prominence
 As the nasal pits deepen, they form nostrils.
o By the 6th week
 The medial and lateral nasal processes appear as horse shoe-shaped elevations with
open end of the slit in contact with oral cavity.
 The medial nasal process: tissue medial to the pit
 Will come together to make 1, forms center part of the nose
 The lateral nasal process: in close contact with maxillary process
 Will form the ala of the nose
 Formation of the upper lip
 By the 6th week…
 2 medial nasal processes merge it the midline to form intermaxillary segment.
 Intermaxillary segment gives rise to:
1. Philtrum- center of upper lip
2. Primary palate
3. Part of the alveolar process carrying the incisor teeth
 Premaxilla- 4 incisors
 Primates have a premaxillary suture, humans do not.
 Later, the segment of the tissue in the center of the lip forms the philtrum.
o Limited laterally by the 2 vertical ridges under the nostrils
o At the lateral boundary of the philtrum, there is a fissure where the line of
fusion of the maxillary and medial nasal process meet.
o There is a vulnerable area of the lip, where a failure to fuse will result in a
cleft lip
o Upper lip is formed by the fusion of 3 parts.
 2 maxillary processes- grow inwardly from the sides
 Medial nasal process – grows downward to interdigidate between
maxillary processes
o Development of facial features
 The continued development of facial features is the result of differential growth brought
by the increase in width of medial and lateral nasal processes.
 By the 7th week
 The face looks more human
 The medial part of the face increases in an anterior direction
 As vertical height increases, the bridge of the nose will develop, therefore, the
nostril and eyes will not be on the same horizontal plane.
 The mouth is very large at the 5th week, but merges at the angles to limit its size
by the 7th week.

4. o Palate Development
 Develops from 3 parts:
 One medial process/primary palate
o Develops as an intermaxillary segment between the maxillary processes
 2 lateral processes
o Develop from the mesial edges of the maxillary processes that bound the
stomodeum (~6 week)
 Lateral palatine processes (shelves) grow medially first, then downward on or
vertical on either side of the tongue.
o The tongue at this point is narrow and tall, almost filling up the oronasal
cavity, and reaches the nasal septum.
o Example: Piere Robin’s Syndrome in which a cleft palate occurs could be
due to failure of tongue to descend and palatine processes cannot fuse.
o The formation begins at the front then fuses like a zipper in a posterior
direction on either side of the tongue.
o Mandible development
 Meckl’s cartilage DOES NOT become bone
 The mandibular nerve determines the shape of the bone, the 1st evidence of calcification
occurs where the mandibular nerve splits into the incisive and mental branch.
Types and Sites of Growth in the Craniofacial Complex
 Bone formation mechanisms- Embryological Stage
o Embryonic cartilaginous model
 4 months in utero- islands of bone appear in a sea of surrounding cartilage. These
islands are the centers of ossification.
 Example: Chondrocranium = cranial base
o Intramembranous bone formation
 Bone forms directly within connect tissue.
 Example: Neurocranium= bones of the cranial vault
 Variables
o Site (location) of growth
 Site of growth= merely a location at which growth occurs.
 Growth centers= location at which genetically controlled growth occurs.
 Nasal septum cartilage- primary cartilage
 Cranial base cartilage (synchondroses)- primary cartilage
 Mandibular condylar cartilage- secondary cartilage.
o Only Meckle’s is primary cartilage
 Functional Matrix
o Example: Zika and microcephaly, hydropcephally and macrocephally
 Intrinsic growth potential ranking of cartilage from high to low:
1) Epiphyseal plates of long bones
2) Synchondroses (cartilage of the cranial base, bands of cartilage found in between
centers of ossification)
3) Cartilage of the nasal septum
4) Mandibular condylar cartilage- very minimal growth
 All centers are sites, but not all sites are centers.
 Sites that are not centers
 Sutures are not primary determinants of craniofacial growth
 Periosteal tissues lacking innate growth potential.
o Types of growth occurring at that site

5. o Determinant (controlling) factors of growth
 Components of craniofacial complex
o Cranial Vault
 Made up of a number of flat bones, formed by intramembranous bone formation
without cartilaginous precursors.
 Example: parietal and frontal bones are formed by intramembranous formation.
Occipital and temporal bones are formed by a mixture of intramembranous
formation and endochondral ossification.
 Growth process is the result of periosteal activity.
 Grows by pulling.
 Periosteal activity occurs in
 Cranial sutures
 Inner and outer surfaces of flat bones
 At birth, flat bones are separated by fontanelles. There are 6 present at birth.
 After birth, appostion of bone coverts the fontanelles to periosteum-lined sutures.
 Primarily, growth in the cranial vault occurs at the sutures
 Secondarily, there is bone removed from the inner surface (resorption), while new bone
is added on the exterior surface (apposition), thus changing the contour.
o Cranial Base
 Bones of the cranial base are formed initially in cartilage, and are later transformed into
endochondral ossification to bone.
 Synchondroses are bands of cartilage found between centers of ossification.
 Intersphenoid synchondroses- ossifies 1st in 1st year of life
 Spheno-ethmoidal synchondroses- ossifies around 6/7- 7/8 years oldose
 Spheno-occipital syndchondroses- ossifies around 13/14- 17/18 years old
 The synchondroses are important growth sites and they represent immovable joints
between the bones of the cranial base.
 The cranial base resembles a single long bone with multiple epiphyseal plate-like
syndrondroses.
 Histologically, the syndchondrosis looks like a 2-sided epiphyseal plate.
o Nasomaxillary complex
 The maxilla develops by intramembranous ossification.
 Growth occurs by:
 Apposition of the bone at the sutures
o Growth is downward and forward due to apposition at the sutures in a
posterior and superior location.
o Resorption occurs on the anterior surface of the maxilla, with a small area
of the anterior nasal spine being the exception.
o Example: Men building a wall on the moving platform
 Surface remodeling (equally important)
 Push from behind created by cranial base growth up until around age 7. Airway?
 Nose comes forward ~0.5 to 0.8mm during growth.
 Translation and remodeling may oppose each other
 Example: anterior part of the alveolar process
 Bone is removed on the anterior surface, partially cancelling out the forward
translation.
 Translation and remodeling may produce an additive affect
 Example: Roof of mouth (palate)
 Moves in the same direction as it is being translated. Bone is removed on the
floor of the nose and added to the roof of the mouth.

6. o Mandible
 Formed by intramembranous ossification
 Bone formation extends anteriorly and posteriorly along Meckel’s cartilage, which is
primary cartilage and serves as a template for bone formation.
 Osteogenesis begins at 6th week and by the 10th week, the mandible is almost entirely
formed by membranous ossifcaiton.
 Spread of mandibular ossification away from Meckel’s cartilage at the lingual. The
Meckel’s cartilage eventually resorbs, but at its most posterior extremity it forms the
malleus of the inner ear, whereas its perichondrium persist at the sphenomandibular
ligament.
 Pre-natal growth of the mandible
 Further growth of the mandible until birth is influenced by the appearance of
secondary cartilages.
o Condylar cartilage
 Present??
 Ossifies until 17-20 years old
o Coronoid cartilage
 Present at 13/15 weeks
 Disappears before birth (ossifies in utero)
o Mental/ Symphyseal cartilage
 Present at 13/14 weeks
 Disappears at 3-9 months
o Gonial cartilage?
 Present at 13/14 weeks
 Disappears before birth
 Post-natal growth of the mandible
 Endochondral and periosteal activity are important
 Endochondral replacement occurs in the mandibular condyle.
 Displacement created by cranial base growth is negligible.
 Sites of mandibular growth
 Condylar process- present until 17-20 years old
 Posterior surface of the ramus
 Coronoid process- 13/15 weeks, disappears before birth
 The body of the mandible grows by periosteal apposition on its posterior surface
 The ramus grows higher by endochondral replacement at the condyle,
accompanied by surface remodeling.
 As a growth site, the chin is almost inactive
 The mandible is translated in a down and forward movement and grows upward and
backward in response to translation, maintaining contact with the skull. There are
minimal changes in the chin and body area. There is exception growth and remodeling
in the ramus, moving it posteriorly.
 Rotation of jaws during growth
 Bjork et al. in Copenhagen, Denmark in the 1960’s pioneered studies that
included placing mini-implants in the context of longitudinal cephalmetric
studies. They concluded… not all mandibles grow the same.
 As growth at the condyle facilitates movement of the mandible forward and
downward, away from the cranial base, a gap is available between the maxilla
and mandible, in which the maxillary and mandibular teeth erupt.
 Types of growth rotation
o Average closing rotation

7.  In most children, condylar growth exceeds molar eruption
 The mandible rotates slightly closed over time
 Posterior face height increases more than anterior face height
 The chin appears more prominent as children age
o Excessive closing during rotation
 In some children, condylar growth greatly exceeds molar eruption
 The mandible rotates more substantially closed.
 A shorter face develops with a deep anterior overbite tendency.
 Forward rotation- brachycephalic- short face- hypodivergent facial
pattern
o Opening during rotation
 Rarely, condylar growth is less than molar eruption and the
mandible rotates open during growth.
 These children demonstrate a long lower face.
 An anterior open-bite tendency exists.
 Backward rotation- dolichocephalic- long face- hyperdivergent
pattern of growth
Theories of Growth Control
 Locus of growth control
o 1. Direct genetic control
 According to this theory, bone, like other tissue is directly under the control of
genetics, which operates from within the tissue.
 This theory is based on the observation that the overall pattern of craniofacial growth is
constant.
 Example: See yourself as a child; you still look the same because the pattern of
growth is constant.
 If true, any attempt to modify facial growth would be futile. It cannot be changed.
o 2. Epigenetic growth control
 According to this theory, cartilage is the primary determinant of skeletal growth and it
indirectly controls growth of the bone. Cartilage grows and is then replaced by bone.
 Transplantation experiments indicate that epiphyseal cartilages and the cranial base
synchondroses do act as growth centers. The nasal septum does to a lesser extent.
 This explains intramembranous growth, but not endochondral ossification.
o 3. Environmental growth control
 According to this theory, the primary determinant of growth is the soft tissue matrix in
which the skeletal elements are embedded; both bone and cartilage are secondary
followers.
 Example: Moss and neural tissue
 Evolution of craniofacial growth theories
o Remodeling theory
 First general theory of craniofacial growth
 Proposed by Brash in the 1930’s
 Bone only grows appositionally
 Maxilla apposition on tuberosity, mandible apposition on posterior
 Jaw growth occurs at the posterior surfaces of the maxilla and mandible
 Growth of cranial vault occurs by ectocranial deposition and endocranial resorptoion
 Sutures and cartilage have little or no role in growth.
o The “sutural” theory
 Weinmann and Sicher in the 1940’s

8.  Sutures as well as cartilage of the craniofacial skeleton are “centers” of growth
 Craniofacial form and facial type are inherited and immutable
 Downward and forward growth of the maxilla is due to the “push” by circummaxillary
suture systems.
 Equal value is attributed to the following by Sicher:
 Sutures
 Cartilage
 Soft tissue
 Periosteum
 Evidence against the sutural theory
 When sutural tissue is transplanted to another location, the tissue does not
continue to grow
 If cranial and facial bones are mechanically pulled apart, the bones will become
larger than they have been otherwise
o Example: RPE or facemask
o RPE opens suture in a fan shape because fuses back to front
 If a suture is compressed, growth at that site will be impeded
o Example: Headgear
 Tissue dominance= sutures
o The nasal septum theory
 Proposed by James Scott in 1950s
 Scott introduced the term “pacemaker” to describe the role of the nasal septum,
cranial base, and condyle
 The nasal septum pulls the face. Example: front wheel drive
 Growth of the nasal septal cartilage pushes the midface downward and forward
relative to the anterior cranial base.
 Separation at sutures fills in with compensatory bone growth
 Sutures are therefore mere “sites” of growth and they play no role in that growth.
They are highly responsive, however, to external force application (example:
headgear)
 Nasomaxillary growth is dependent upon normal growth of the nasal septal
cartilage.
 Condylar cartilage contributes to mandibular growth by pushing the mandible
downward and forward.
 Tissue dominance: cartilage
o In summary
 Both the sutural and nasal septum theory assume that CF growth is largely inherited
and immutable (genomic paradigm)
 Both theories agree that cartilages (cranial base synchondroses, nasal septal
cartilage, and condylar cartilage) posses intrinsic, genetically controlled growth
potential (growth centers) expressed to varying degrees
 There is a disagreement with respect to the role of the sutures
 The sutural theory views sutures are growth “centers”
 Center= tissue separating capabilities, under genetic control
 The nasal septum theory views sutures as growth “sites”
 Sites= active skeletal growth, secondary, compensatory
 The clinical implications in terms of orthodontics are obvious
o Functional Matrix theory of growth
 Proposed by Moss in the 1960s

9.  Moss theorized that growth of the face occurs as a response to functional needs and
neurotrophic influences, and is mediated by the soft tissue in which the jaws are
embedded.
 Initial stages of growth are subject to genetic control
 Subsequently, form follows function (Wolff’s law)
 Two types of functional matrices:
 1. Capsular (encapsulated volumes)- organs, eyes, brain, spaces such as
nasopharynx and oropharynx
 2. Periosteal (muscle pull)- local environment such as muscles, blood vessels
and nerves
 in 75-50% of children with condylar fractures, the loss of the condyle does not
impede mandibular growth, provided proper function exists.
 Loss of function secondary to ankylosis brought about by trauma or infection may
lead to mandibular growth deficiency.
 Is the condyle a growth center??
 Tissue dominance= soft tissue (functional matrix)