This document discusses prenatal and postnatal craniofacial growth and implications for craniofacial syndromes. It covers the five principal stages of craniofacial development from germ layer formation through final tissue differentiation. Specific syndromes like fetal alcohol syndrome, Treacher Collins syndrome, and hemifacial microsomia are discussed in context of when disruptions occur during development. Cleft lip, cleft palate, and other clefting issues are examined including causes, types, prevalence, diagnosis, and multidisciplinary treatment approaches throughout development.

1. Prenatal and Postnatal Craniofacial
Growth: Implications for Craniofacial
Syndromes
Christos Vlachos,DMD,MS

2. Embryology Video
 https://www.youtube.com/watch?v=FhhW
G3XzARY

4. • Most facial tissues originate from ectoderm
• In particular, from neural crest cells that migrate downward
beside the neural tube and laterally under the surface ectoderm
Embryologic Development: Broad Overview
Courtesy Dr. Souccar

5. Embryologic
Development
There are five principal
stages in craniofacial
development

6. Stages in Craniofacial Development
 1st- Germ layer
formation and initial
organization of
craniofacial structures
 2nd- Neural tube
formation and initial
formation of the
oropharynx
Courtesy Dr. Souccar

7.  3rd- Origins, migrations,
and interactions of cell
populations
 4th- Formation of organ
systems
 5th- Final
differentiation of
tissues
Stages in Craniofacial Development
Gammill LS, Bronner-Fraser M. Neural crest specification:
migrating into genomics. Nature Reviews Neuroscience 2003, 4:
795-805 (
Courtesy Dr. Souccar

8.  Initiation of the oral cavity occurs in the 3rd prenatal week as a
pit or invagination of 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 form the lower part of the
face and neck.

13. Facial development
• The face develops during 5th~7th
prenatal week from 4 primordia
that surround a central depression
known as central pits
▫ Frontal process:
- Single process located cranially
- Give rise to upper face
▫ 2 Maxillary processes:
- Arise from 1st pharyngeal arch
▫ Mandibular process:
- Initially appears partially
divided, but then soon merges at
midline to form a single structure
- Gives rise to mandible, lower
part of face and body of tongue.

15.  By the end of 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.
- - These depressions are called “nasal
pits”.
- - The area where nasal pits appear is
called “frontonasal prominence”
- - As the nasal pits deepen, they form
nostrils

17. By 6th week
- The medial and lateral nasal process appear as horse-shaped elevations with
open end of the slit in contact with oral cavity.
- The medial nasal process: tissue medial to the pit
- The lateral nasal process: tissue lateral to the pitmaxillary process

19. Formation of upper lip
 By 6th weeks:
- 2 medial nasal processes merge in midline to form intermaxillary
segment
- The Intermaxillary segment gives rise to :
- Center of the upper lip
- Primary palate
- Part of alveolar process carrying the incisor teeth

20. - Later, the segment of the tissue in the center of the lip forms the
philtrum
- Limited laterally by the two vertical ridges under the nostrils
- At the lateral boundary of the philtrum, there is a fissure where
the line of fusion of maxillary and medial nasal process meet.
- This is a vulnerable area of the lip, failure to fuse will result in a cleft lip
- Upper lip is composed by the fusion of 3 parts:
- 2 maxillary processes: grow inwardly from the sides
- Medial nasal processes: grow downward

22. 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 7th week:
- The face looks more like human
- The medial part of the face increases in anterior direction
- As vertical height increases, the bridge of the nose will develop, therefore
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 7th week

23. Palate development
• Develops from 3 parts:
▫ One medial process/ primary palate
 develops as an intermaxillary segment between the
maxillary processes
▫ 2 lateral processes
 Develop from the medial edges of the maxillary processes
that bound the stomodeum (~6 wk).
• Lateral palatine processes (shelves) grow
medially first, then downward or vertically on
either side of the tongue
▫ The tongue at this point is narrow and tall almost
filling the oronasal cavity, and reaches the nasal
septum.

33. Embryologic Development

34. Some specific abnormalities in facial
form and jaw relationships can be
traced to certain stages of
development.

35. Germ Layer Formation and Initial
Organization of Structures
(1st Stage)
 Fetal Alcohol Syndrome (FAS)

36. Fetal Alcohol Syndrome
 Deficiencies of midline
tissue of the neural
plate very early in
embryonic development
 Caused by exposure to
very high levels of
ethanol
 Implicated in many
cases of maxillary and
midface deficiency

37. Origin, Migration, and Interaction of
Cell Populations (3rd Stage)
 Treacher Collins Syndrome (Mandibulofacial
dysostosis)
 Hemifacial Microsomia

38. Treacher Collins Syndrome
 Results from an altered neural crest
development
 Both maxilla and mandible are underdeveloped
bilaterally as a result of generalized lack of
mesenchymal tissue
 Arises because of excessive cell death in the
trigeminal ganglion, which secondarily affects
neural crest cells

39. Treacher Collins
Syndrome

40. 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 from early loss of neural crest cells
 Defects in the great vessels (ex. Tetralogy of Fallot)
are commonly affected
 Caused by lack of neural crest cells migrating to lower
regions

41. Hemifacial Microsomia

42. Drugs that Affect Formation
and/or Migration of Neural Crest
Cells
 Thalidomide
 Accutane

43. Formation of Organ Systems
(4th Stage)
 Cleft lip and/or palate (CL/P)
 Cleft palate (CP)

44. Final Differentiation of Tissues
(5th Stage)
 Synostosis Syndromes (result from early closure
of sutures between cranial and facial bones)
• Crouzon’s syndrome

45. Crouzon’s Syndrome
 Underdevelopment of the midface and eyes
that seem to bulge from their sockets
 Its due to prenatal fusion of the superior
and posterior sutures of the maxilla, along
the wall of the orbit, and often the cranial
vault

46. Crouzon’s Syndrome

47. Late Fetal Development and Birth
 During the last 3 months of intrauterine
life, continued rapid growth results in a
tripling of body mass
 Development of all primary teeth and the
permanent first molars starts well before
birth
 During birth the head is increased in length
and decreased in width to facilitate
passage through the birth canal

48. Late Fetal Development and Birth
 The lack of lower jaw growth prenatally also facilitates birth
 Postnatally, the mandible grows more than 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 bones and
teeth that are forming at that time
 Growth disturbances lasting 1-2 weeks or more caused by
either birth or febrile illness later can also result in visible
records in the enamel

49. CLEFTS

50. Diagnostic Considerations
 Clefts of the lip and palate occur in 1/700 live births in
the US
 Among the most common craniofacial birth defects
 Environmental and genetic factors
– Facial development largely occurs between the 4th and
8th weeks of pregnancy
• Events that cause hypoxia early during pregnancy
(maternal smoking, alcohol consumption, drug use,
exposure to pesticides, disease etc.) can lead to
deformation
• Many syndromes have a genetic component (Pierre
Robin Sequence, Apert Syndrome, Crouzon
Syndrome, Treacher Collins Syndrome, Velo-
cardio-facial Syndrome)

51. Prenatal Diagnosis of Cleft
Lip/Palate
 Craniofacial cleft may be diagnosed by prenatal
ultrasound
 Non-invasive diagnostic tool
 Cleft lip easier to diagnose than cleft palate
– 38-73% detection rate for facial clefting
– Cleft palate detection rates as low as 1.4%
 Detection rate improved when transabdominal
ultrasound performed at or after 20 weeks

53. Unilateral Cleft Lip
 Failure of the
maxillary process on
one side to meet
and fuse with the
medial nasal process;
resulting in division
of the lip into medial
and lateral parts
 Results in nasal
distortion due to a
pull on lip and nasal
tissues towards
unaffected side.

54. Unilateral Cleft Lip

55. Bilateral Cleft Lip
 Occurs as the unilateral
but on both sides. The
medial mass interposed
between the 2 maxillary
processes grows down
from the lateral areas
from above the
maxillary processes.
 Defects can be
symmetrical or
asymmetrical

56. Bilateral Cleft Lip and Palate

57. Median Cleft Lip/ “Hare Lip”
 Results from partial
or complete failure
of the medial nasal
processes to merge.
 extremely rare

58. Median Cleft of the Mandible
 Very rare
 Results from failure
of the mesenchymal
masses of the
mandibular
processes to merge
together at 5 weeks
of intrauterine life.

59. Submucous cleft
 Palatal soft tissues close,
but the bony palate
doesn’t
 Bony defect in the midline
or center of the bony
palate covered over by the
lining (mucous membrane)
of the roof of the mouth
 Midline deficiency or lack
of muscular tissue and
incorrect positioning of
the muscles.
 Possible sign of submucous
cleft: Bifid uvula

60. Clefts of the Primary Palate
• Clefts anterior to the
Incisive foramen
• Involves alveolar crest
• Result from failure of
the lateral palatine
process to meet and
fuse with the median
palatine process or
primary process.
• Usually associated with
missing or malformed
teeth adjacent to cleft:
laterals and cuspids.

61. Secondary Palate/ Soft palate
Cleft
 Clefts posterior to
the Incisive foramen
 Result from partial
or complete failure
of the lateral
palatine processes to
meet, fuse and
merge with each
other and with the
nasal septum.
Bifid Uvula

62. Complete Palatal Cleft/
Primary and Secondary Palate
Cleft
 Result from failure
of growth or lack of
fusion of the three
palatine processes
with each other and
with the nasal
septum.

63.  Incidence:
– Cleft lip alone – 10%
– Cleft palate alone – 30%
– Unilateral CLP – 40%
– Bilateral CLP – 10%
– Other cleft (submucous cleft, bifid uvula) – 10%
 Incidence of orofacial clefts varies by ethnicity
– Asians (14:10,000 births)
– Caucasians (10:10,000 births)
– African Americans (4:10,000 births)
 Prevalence of the cleft type varies by gender
– CLP - male : female 2:1
– CP - male : female 2:3
– CL - male : female 2:1
How Common is Orofacial Clefting?

64. Treatment
• Dental specialties
• Orthodontics
• Oral surgery
• Pediatric dentistry
• Prosthodontics
• Medical specialties
• Genetics
• Otolaryngology
• Pediatrics
• Plastic surgery
• Psychiatry
 Allied health care fields
• Audiology
• Nursing
• Psychology
• Social work
• Speech pathology
COMMUNICATION
IS CRUCIAL

65. Developmental Stages
• Neonate /Infant stage (Birth to 2 yrs)
• Primary dentition stage (2 to 6 yrs)
• Mixed Dentition Stage (7 to 12 yrs )
• Permanent Dentition Stage (13 to 21)

66. Neonate/Infant Stage
• Infant Orthopedics (1st or 2nd week )
• Surgical Lip repair (3 to 6 months)
• Palatal surgery (12 to 24 monrths)
• Primary bone grafting rarely advocated

67. Infant Orthopedics
• Popular in the 60’s and 70’s
• Remains controversial
• Questionable long term benefits
• Objective:Alignment of palatal segments to
a more ideal relationship prior to surgical
lip repair

68. Infant Orthopedics (cont.)
• Alveolar molding plate
• Naso Alveolar Molding(NAM) is essentially a
molding plate with a nasal stent
• Latham appliance
• Claims for positive impact on
speech,nutrition,occlusion or growth of the
midface have not been substantiated.

69. Nasoalveolar Molding Appliance
(NAM)
 Expands soft tissue to correct nasal
deformities and columellar length
 Purported to minimize the extent of surgery
or number of surgical procedure

70. Naso Alveolar Molding(NAM)

71. Pre-NAM Post-NAM

72. Fixed appliances
 Dentomaxillary advancement (DMA) for
unilateral CLP
 Elastic chain premaxillary repositioning
appliance (ECPR) for bilateral CLP –
Latham appliance

73. Latham appliance

74. Primary bone Grafting
• Has been advocated in conjunction with
infant orthopedics with the rationale to
stabilize and prevent maxillary collapse.
• Long-term growth of the maxillary
complex and occlusion appear similar to
cases without this intervention.

75. Surgical Lip Repair
• Typically carried out at about 3 months of age
• Rule of tens(10 wks,10 lbs,10 mg Hb,10,000 wbc)
• Primary surgical lip repair, ideally, restores
continuity of the mucosa ,skin, and circumoral
musculature with a single procedure
• At times it is preceded by surgical lip adhesion(i.e.
partial lip repair reserved for wide,complete clefts)

76. Surgical Lip Repair-Cheiloplasty

77. Palatal Closure (Repair)
• Typically carried out between the ages of 12 and 24
months
• Controversial issue
• Speech pathologists recommend early palatal
closure because language skills develop
dramatically around the first year of age
• Early repair of the palate,however, and the resulting
scar tissue may restrict maxillary growth.

80. PRIMARY DENTITION STAGE
• Crossbite often present (Unilateral or Bilateral,with or
without a functional shift of the mandible)
• Maxillary expansion as well as growth modification has
been advocated,including face protraction mask
• No strong evidence supports a benefit from routinely
treating malocclusions in the primary dentition
• In view of the fact that multiple interventions are
anticipated in the management of CLP patients, it is best
to defer orthodontic treatment at a later time

81. MIXED DENTITION STAGE
• As the permanent incisors erupt adjacent to the cleft site,
typically, they are rotated,misplaced,malformed or
hypoplastic.
• V-shaped maxillary arch form,usually associated with
psterior and/or anterior crossbite
• Lack of tissue is the predominant feature
• The advent of secondary (delayed) alveolar bone grafting
procedure in the 70’s is a milestone in the management of
alveolar cleft

82. Secondary alveolar cleft bone graft
a. Provides bony support for the teeth adjacent
to the cleft to erupt
b. Offers maxillary continuity
c. Aids in the closure of the oronasal fistula
d. Supports the alar base of nose
e. Facilitates total habilitation: speech, dental
esthetic and psychosocial benefits
f. Canine can be successfully erupted through
cleft once the cleft alveolus is bone-grafted

83. Early vs Late Secondary alveolar
bone grafting
• It is generally recommended that the graft be placed
before the eruption of the permanent canine.
• Some advocate early placement (7 to 9 yrs of age) such
as when the lateral incisor is present at the distal site of
cleft.
• Others opt for a later placement of the graft (9 to 11 yrs of
age), citing less interference with maxillary development
• Secondary bone grafting should precede Distraction
Osteogenesis

84. Distraction Osteogenesis (RED System)
• In 1992,McCarthy et al.,introduced the use of DO in
the craniofacial skeleton
• It involves a Rigid External Distraction (RED) device
attached to an intraoral maxillary splint.The maxilla is
mobilized via a Le-Fort I osteotomy
• Rate of distraction is 1-2 mm /day. Correction takes
2-3 weeks
• After removal of the halo ,a face protraction mask is
used for 6-8 weeks(?)

91. Distraction Osteogenesis (RED System)
• It was meant to be a substitute for Orthognathic
Surgery in moderate deformity cases.This was
not always the case.
• It was meant to provide ultimately more stability
in patients with severe deformity, who
eventually underwent conventional OG Sx.
• Best timing for DO has not been established.

97. PERMANENT DENTITION STAGE
• A decision should be made whether the malocclusion
can be treated by orthodontics alone or in conjunction
with Orthognathic Surgery
• Camouflage treatment involving extractions of
premolars may be adequate to compensate for the
deformity present
• Unfortunately in some instances,the individual may
outgrow the dental correction so that ultimately
Orthognathic Sx. is recommended

105. ACKNOWLEDGEMENTS
 Dr. Nada Souccar
 Dr. Lionel Sadowsky
 Dr. Nat Robin
 Department of Pediatric Dentistry