3. 1. Differentiation
A Single Cell, the Fertilized
Egg, Gives Rise to Hundreds
of Different Cell Types. This
Generation of Cellular Diversity
Is Called Differentiation.
ikassem@dr.com
8. Developmental
Regulatory genes are
Transcription factors
Transcription factors or gene regulatory proteins
are involved in activating or repressing transcription.
TFs act by binding to the control regions of genes
or by interacting with other DNA-binding proteins.
ikassem@dr.com
11. Congenital Malformations
Causes
– Genetic/chromosomal
– Enviornmental
Incidence
– 2-3% of newborn (4-6% by age 5)
– In 40-60% of all birth defects cause is
unknown
Genetic/chromosomal
– 10%-15%
Environmental
– 10%
Multifactorial (genetic & environmental)
– 20%-25% ikassem@dr.com
12. Teratology
Teratology
– Science that studies the causes of abnormal
development
– The term is derived from the Greek ―teratos‖
which means monster
– Birth defects is the number one cause of
infant mortality
ikassem@dr.com
13. Terms used in Disease
Sign objective evidence of a disease
Symptom subjective evidence of a
disease
Syndrome refers to a set of symptoms
& signs which occur together in the
morbid (disease) state
Etiology the study of the cause of
disease
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14. Types of Anomalies
Malformations
– Occur during formation of structures
Complete or partial absence
Alterations of its normal configuration
Disruptions
– Morphological alterations of structures after
formation
Due to destructive processes
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15. Deformations
– Due to mechanical forces that mold a part of
fetus over a prolonged period of time
Clubfeet due to compression in the amniotic cavity
Often involve the musculoskeletal system & may
be reversible postnatally
Syndromes
– Group of anomalies occuring together with a
specific common etiology
Diagnosis made & risk of recurrence is known
ikassem@dr.com
17. Infectious Agents
Rubella (German Measles)
– Malformations of the eye
Cataract (6th week)
Microphthalmia
– Malformations of the ear (9th week)
Congenital deafness
– Due to destruction of cochlea
– Malformations of the heart (5th -10th week)
Patent ductus arteriosis
Atrial septal defects
Ventricular septal defects
ikassem@dr.com
18. Cytomegalovirus
– Disease is often fatal early on
– Malformations
Microcephaly
– Cerebral calcifications
– Blindness
Chorioretinitis
– Kernicterus (a form of jaundice)
– multiple petechiae of skin
– Hepatosplenomegaly
– Mother asymptomatic
ikassem@dr.com
19. Herpes Simplex Virus
– Intrauterine infection of fetus occasionally occurs
– Usually infection is transmitted close to time of
delivery
– Abnormalities (rare)
Microcephaly
Microphthalmos
Retinal dysplasia
Hepatosplenomegaly
Mental retardation
– Usually child infected by mother at birth
Inflammatory reactions during first few weeks
ikassem@dr.com
20. Varicella (chickenpox)
– Congenital anomalies
20% incidence following infection in 1st trimester
Limb hypoplasia
Mental retardation
Muscle atrophy
HIV/AIDS
– Microcephaly
– Growth retardation
– Abnormal facies (expression or appearance of
the face)
ikassem@dr.com
21. Toxoplamosis
– Protozoa parasite (Toxoplama gondii)
Sources
– Poorly cooked meat
– Domestic animals (cats)
– Contaminated soil with feces
Syphilis
– Congenital deafness
– Mental retardation
– Diffuse fibrosis of organs (eg. liver & lungs)
In general most infections are pyrogenic
– Hyperthemia can be teratogenic
Fever
Hot tubs & Saunas
ikassem@dr.com
22. Radiation
Teratogenic effect of ionizing radiation
well established
– Microcephaly
– Skull defects
– Spina bifida
– Blindness cleft palate
– Extremity defects
Direct effects on fetus or indirect effects
on germ cells
May effect succeeding generations
Avoid X-raying pregnant women
ikassem@dr.com
23. Chemical agents/Drugs
Role of chemical agents & drugs in
production of anomalies is difficult to assess
– Most studies are retrospective
Relying on mother’s memory
– Large # of pharmaceutical drugs used by
pregnant women
NIH study – 900 drugs taken by pregnant women
– Average of 4/woman during pregnancy
– Only 20% of women use no drugs during pregnancy
– Very few drugs have been positively identified
as being teratogenic
ikassem@dr.com
24. Drugs
Thalidomide
– Antinauseant & sleeping pill
– Found to cause amelia & meromelia
Total or partial absence of the extremities
– Intestinal atresia
– Cardiac abnormalities
– Many women had taken thalidomide early in
pregnancy (in Germany in 1961)
ikassem@dr.com
25. Anticonvulsants (to treat epilepsy)
– Diphenylhydantoin (phenytoin)
Craniofacial defects
Nail & digital hypoplasia
Growth abnormalities
Mental deficiency
The above pattern is know as ―fetal hydantoin
syndrome‖
– Valproic acid
Neural tube defects
Heart defects
Craniofacial & limb anomalies
ikassem@dr.com
26. Antipsychotic drugs (major tranquilizers)
– Phenothiazine & lithium
Suspected teratogenic agents
Antianxiety drugs (minor tranquilizers)
– Meprobamate, chlordiazepoxide,
Severe anomalies in 11-12% of offspring where
mothers were treated with the above compared to
2.6% of controls
– diazepam (valium)
Fourfold in cleft lip with or without cleft palate
ikassem@dr.com
27. Anticoagulants
– Warfarin (A.K.A cumadin or cumarol)
Teratogenic
Hypoplasia of nasal cartilage
Chondrodysplasia
Central nervous system defects
– Mental retardation
– Atrophy of the optic nerves
Antihypertensive agents
– angiotensin converting enzyme (ACE) inhibitor
Growth dysfunction, renal dysfunction,
oliogohydramnios, fetal death
ikassem@dr.com
28. Isotretinoin (13-cis-retinoic acid)
– Analogue of vitamin A
– Drug is prescribed for treatment of cystic acne
& other chronic dermatoses
– Highly tertogenic
Reduced & abnormal ear development
Flat nasal bridge
Cleft palate
Hydrocephaly
Neural tube defects
Heart anomalies
ikassem@dr.com
30. Alcohol
Relationship between alcohol consumption
& congenital abnormalities
Fetal alcohol syndrome
– Craniofacial abnormalities
Short palpebral fissures
Hypoplasia of the maxilla
– Limb deformities
Altered joint mobility & position
– Cardiovascular defects
Ventricular septal abnormalites
– Mental retardation
– Growth deficiency
ikassem@dr.com
31. Cigarette Smoking
Has not been linked to major birth defects
– Smoking does contribute to intrauterine
growth retardation & premature delivery
– Some evidence that is causes behavioral
disturbances
ikassem@dr.com
32. Maternal Disease
Disturbances in CHO metabolism (diabetic
mothers)
– High incidence of stillbirth, neonatal deaths
– Abnormally large infants
– Congenital malformations
risk 3-4X
Cardiac, Skeletal, CNS Anomalies
Caudal dysgensis
– Partial or complete agenesis of sacral vertebrae in
conjuction with hindlimb hypoplasia
– Hypoglycemic episodes teratogenic (why?)
– Oral hypoglycemic agents maybe
teratogenic
ikassem@dr.com
33. Hypoxia
Associated with congenital malformations
in a great variety of experimental animals
– In humans ???
Maybe smaller babies e.g. offspring at high
altitude
ikassem@dr.com
35. Prevention of birth defects
Good prenatal care
Iodine supplementation eliminates mental
retardation & bone deformities
– Prevent cretinism
Folate/Folic Acid supplementation
– incidence of neural tube defects
Avoidance of alcohol & other drugs during
all stages of pregnancy
– incidence of birth defects
ikassem@dr.com
37. Chromosomal Abnormalities
May be numerical or structural
Important causes of congenital
malformations & spontaneous abortions
Estimated that 50% of all conceptions end
in spontaneous abortion & 50% of these
have major chromosome abnormalities
Most common chromosome abnormalities
in aborted fetuses is:
– Turner syndrome (45,X)
– triploidy
– trisomy 16
ikassem@dr.com
38. Numerical Abnormalities
Normal gametes are haploid (n =23)
Normal human somatic cell contains 46
chromosomes; Diploid (2n = 46)
Euploid-Exact multiple of n
Aneuploid-Any chromosome # that is noneuploid
– Additional chromosome
– Missing chromosome
Most common cause is nondisjunction during
either meiosis to mitosis
– Risk of meiotic nondisjunction with maternal age
ikassem@dr.com
39. Structural Abnormalities
May involve one or more chromosomes
Usually result from chromosome breakage
– Broken piece may be lost
Partial deletion of chromosome 5
– Cri-du-chat (cry of the cat)
Microcephaly
Mental retardation
Congenital heart disease
Many other relatively rare syndromes
result from a partial chromosome loss
ikassem@dr.com
40. Mutant Genes
Many congenital malformations are
inherited
– Some show a clear mendelian pattern of
inheritance
– In many cases abnormality is attributed to a
change in the structure or function of a single
gene. ―single gene mutation‖
– Estimated that this type of defect makes up
about 8% of all human malformations
– Dominant vs. recessive vs. X-linked (also
recessive)
ikassem@dr.com
42. Head formation
rostral or head fold
anterior portion of the neural tube
expands as the forebrain, midbrain
and hindbrain
the neuroectoderm in this region will
form the olfactory, orbital and
otic placodes
the hindbrain forms 8 bulges =
rhombomeres
the paraxial mesoderm in this region
also segments into somites
migration of neural crest cells into
this region provides the embryonic
connective tissue (mesenchyme)
required for development of the
craniofacial structures
these neural crest cells arise from the
midbrain and the first two
rhombomeres as two streams
ikassem@dr.com
43. Branchial arches
also called pharyngeal arches
figure 4-11
fourth week: development of a
frontal prominence forms the
stomatodeum
below this is the formation of the
first branchial arch
(mandibular arch)
6 pairs – U shaped
– core of mesenchymal tissue
formed from neural crest cells that
migrate in to form the arches
– covered externally by ectoderm
and lined internally by endoderm
– each has its own developing
cartilage, nerve, vascular and
muscular components
these arches separate the
stomatodeum from the developing
heart
ikassem@dr.com
44. Branchial arches
separated laterally by branchial grooves/clefts
medially they are separated by pharyngeal pouches
first arch (mandibular arch) – maxillary and mandibular
processes
second arch (hyoid arch) - hyoid bone, part of the temporal bone
(VII nerve)
cartilage = Reichert’s cartilage
the mesoderm of this arch will form the muscles of facial expression, the
middle ear muscles
third arch –tongue (IX nerve)
fourth arch –tongue, most of the laryngeal cartilages (IX and X
nerves)
fifth arch – becomes incorporated into the fourth
sixth arch – most of the laryngeal cartilages (IX and X nerves)
ikassem@dr.com
45. Pharyngeal Pouches
– four well-defined pairs of pharyngeal pouches develop from
the lateral walls of the pharynx
– first pouch (betwen the 1st and 2nd arches) - external acoustic
meatus, tympanic membrane, and eustachian tube
– second pouch – palatine tonsils
– third pouch - thyroid and parathyroid glands,
– fourth pouch – parathryoid gland
– fifth pouch -becomes incorporated into the fourth
ikassem@dr.com
46. Development of the Face
forms from the fusion of 5 face primordia
which develop during week 4 and fuse
during weeks 5 through 8
– primordia = ectodermal swellings or
prominences that are filled with mesodermal
and neural crest cells
frontonasal prominence
mandibular prominences (2) – from branchial
arch #1
maxillary prominences (2) – from branchial
arch #1
ikassem@dr.com
49. Upper lip formation
during the fourth week
fusion of the maxillary processes with
each medial nasal process
this contributes to the lateral sides of
the upper lip – together with the
medial nasal processes which
contribute to the medial aspect of the
upper lip
the maxillary processes also fuse with
the lateral nasal processes – results in
a nasolacrimal groove which
extends from the medial corner of the
eye to the nasal cavity
ikassem@dr.com
50. Development of the Palate
involves the formation of a
primary palate, a secondary palate
and fusion of their processes
Primary palate
– forms from an internal swelling of the
intermaxillary/premaxillary process
(fusion of medial nasal processes)
Secondary palate
– forms from the two lateral palatine
shelves or processes
– develop as internal projections of the
maxillary prominences
ikassem@dr.com
51. Primary palate
fusion of the
median nasal
processes gives rise
to the median
palatine process –
fuses to form the
primary palate
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52. Secondary Palate
the common oronasal cavity is bounded
anteriorly by the primary palate and
occupied by the developing tongue
only after the development of the
secondary palate can oral and nasal
cavities by distinguished
three outgrowth appear in the oral cavity
– nasal septum:
grows downward through the oral cavity
it encounters the primary and secondary
palates
– two palatine shelves
closure of the secondary palate is likely
to involve the hardening of the palatine
shelves – mechanism remains unknown
+ the withdrawl of the tongue
ikassem@dr.com
53. Maxilla formation
centers of ossification develop in the mesenchyme of the maxillary
processes of the first branchial arch
spreads posteriorly below the orbit towards the developing zygoma and
anteriorly toward the future incisor region and superiorly to form the
frontal process
ossification also spreads into the palatine process to form the hard palate
at the union between the palatal process and the main body of the
developing maxilla is the medial alveolar plate – together with the
lateral plates – development of the maxillary teeth
a zygomatic or malar cartilage appears in the developing zygomatic
processes and contributes to the development of the maxilla
ikassem@dr.com
54. Mandible formation
the cartilage of the first branchial arch
associated with the formation of the
mandible = Meckel’s cartilage
6 weeks: Meckel’s cartilage forms a rod
surrounded by a fibrocellular capsule
the two cartilages do not meet at the midline
but are separated by a thin line of cartilage =
symphysis
on the lateral aspect of this symphysis – a
condensation of mesenchyme forms
at 7 weeks intramembranous ossification
begins in this mesenchyme and spreads
anteriorly and posteriorly to form the bone
of the mandible
the bone spreads anteriorly to the midline of
the developing lower jaw – the bones do not
fuse at the midline – mandibular symphysis
forms (from meckel’s cartilage)
– which fuses shortly after birth
the ramus develops from rapid ossification
posteriorly into the mesenchyme of the first
arch
ikassem@dr.com
55. Mandible formation
-Meckel’s cartilage does NOT contribute directly to the ossification of
the mandible
-posterior extremity – malleolus of the inner ear
-portion persists as the sphenomandibular ligament
-significant portion is resorbed entirely
-most anterior portion near the midline may contribute to the jaw
through endochondral ossification
-growth of the mandible until birth is influences by the appearance of
three secondary (growth) cartilages
1. condylar – 12th week, developing ramus by endochondral
ossification, a thick layer persists at birth at the condylar head
(mechanism for post-natal growth of the ramus = endochondral)
2. coronoid – 4 months, disappears before birth
3. symphyseal – appears in the connective tissue at the ends of the
Meckel’s cartilage, gone after 1 year after birth
ikassem@dr.com
56. Development of the Tongue
begins to develop about 4 weeks
localized proliferation of the
mesenchyme results in formation of
several swellings in the floor of the oral
cavity
the oral part (anterior two-thirds)
develops from the fusion of two distal
tongue buds or lateral lingual
swellings and a median tongue
bud (tuberculum impar)
the pharyngeal part or root of the
tongue (posterior one-third) develops
from the copula and the
hypobranchial eminence (forms
from the 2nd, 3rd and 4th branchial
arches)
these parts fuse (adult = terminal
sulcus)
muscles of the tongue arise from
occipital somites which migrate into
the tongue area
hypobranchial arch
overgrows the 2nd arch
B.As #1,2 and 3
ikassem@dr.com
57. There are many developmental
abnormalities that can affect the teeth and
facial skeleton. In most cases, clinicians
need little more than to be able to
recognize these abnormalities
ikassem@dr.com
64. Missing teeth
• Localized anodontia or hypodontia —
usually third molars, upper lateral incisors or
second premolars.
• Anodontia or hypodontia associated with
systemic disease — e.g. Down's syndrome,
ectodermal dysplasia.
ikassem@dr.com
65. Additional teeth (hyperdontia)
• Localized hyperdontia — Supernumerary
teeth
— Supplemental teeth
• Hyperdontia associated with specific
syndromes, e.g. cleidocranial dysplasia,
Gardener's syndrome.
ikassem@dr.com
66. Anomalies of the teeth
1-Number
2-Structure
3-Size
4-Shape
5-Position.
ikassem@dr.com
69. Acquired defects
• Turner teeth — enamel defects caused by
infection from overlying deciduous predecessor
• Congenital syphilis — enamel hypoplastic and
altered in shape (see below)
• Severe childhood fevers, e.g. measles —
linear
enamel defects
Fluorosis — discolouration or pitting of the
enamel
• Discolouration — e.g. tetracycline staining.
ikassem@dr.com
70. Anomalies of the teeth
1-Number
2-Structure
3-Size
4-Shape
5-Position.
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71. 3-Abnormalities in size
• Macrodontia — large teeth
• Microdontia — small teeth, including
rudimentary teeth.
ikassem@dr.com
72. Anomalies of the teeth
1-Number
2-Structure
3-Size
4-Shape
5-Position.
ikassem@dr.com
74. Anomalies affecting -whole
teeth
• Fusion — two teeth joined together from the
fusion of adjacent tooth germs
• Gemination — two teeth joined together but
arising from a single tooth germ
• Concrescence — two teeth joined together by
cementum
• Dens-in-dente (invaginated odontome) — in
folding of the outer surface of a tooth into the
interior usually in the cingulum pit region of
maxillary lateral incisors.
ikassem@dr.com
75. Anomalies affecting the
crowns
• Extra cusps
• Congenital syphilis
— Hutchinson 's incisors — crowns small,
screwdriver or barrel-shaped, and often
notched
— Moon's/mulberry molars — dome-shaped or
modular
• Tapering pointed incisors — ectodermal
dysplasia.
ikassem@dr.com
76. Anomalies affecting roots and
or pulp canals
• Number — additional roots, e.g. two-rooted
incisors, three-rooted premolars or four-rooted
molars
• Morphology, including:
— Bifid roots
— Excessively curved roots
— Dilaceration — sharp bend in the root
direction
— Taurodontism — short, stumpy roots and
longitudinally enlarged pulp chambers
Pulp stones — localized or associated with
specific syndromes, e.g. Ehlers-Danlos (floppy
joint syndrome).
ikassem@dr.com
77. Odontomes
• Enameloma/enamel pearl
• Cementoma (see fibro-cemento-osseousmesions in
— Benign cementoblastoma (true cementoma)
— Periapical cemento-osseous dysplasia
— Focal cemento-osseous dysplasia
— Florid cemento-osseous dysplasia
(gigantiform cementoma)
• Composite
— Compound odontome — made up of one or more
small tooth-like denticles
— Complex odontome — complex mass of disorganized
dental tissue.
ikassem@dr.com
78. Anomalies of the teeth
1-Number
2-Structure
3-Size
4-Shape
5-Position.
ikassem@dr.com
80. Delayed eruption
• Local causes
— Loss of space
— Abnormal crypt position — especially 8/8 and 3/3
— Overcrowding
— Additional teeth
— Retention of deciduous predecessor
— Dentigerous and eruption cysts
• Systemic causes
— Metabolic diseases, e.g. cretinism and rickets
— Developmental disturbances, e.g. cleidocranial dysplasia
— Hereditary conditions, e.g. gingival fibromatosis and
cherubism.
ikassem@dr.com
81. Other positional anomalies
• Transposition two teeth occupying
exchanged positions
• Wandering teeth, movement of unerupted
teeth for no apparent reason (distal drift)
• Submersion, second deciduous molars
apparently descend into the jaws. Since these
teeth do not in fact submerge, but rather
remain in their original position while the
adjacent Other positional anomalies
ikassem@dr.com
83. Abnormalities of the mandible
or maxilla
Micrognathia
Macrognathia (prognathism)
Other mandibular anomalies
ikassem@dr.com
84. Micrognathia
• True micrognathia — usually caused by bilateral
hypoplasia of the jaw or agenesis of the condyles
• Acquired micrognathia — usually caused by
unilateral early ankylosis of the
temporomandibular joint.
ikassem@dr.com
85. Macrognathia
(prognathism)
• Genetic
• Relative prognathism — mandibular/maxillary
disparity
• Acquired, e.g. acromegaly owing to excessive
growth hormone from a pituitary tumour.
ikassem@dr.com
87. Cleft lip and palate
• Cleft lip
— Unilateral, with or without alveolar ridge
— Bilateral, with or without alveolar ridge
• Cleft palate
— Bifid uvula
— Soft palate only
— Soft and hard palate
• Clefts of lip and palate (combined defects)
— Unilateral (left or right)
— Cleft palate with bilateral cleft lip.
ikassem@dr.com
93. Stages of tooth
development
1. Bud stage
2. Cap stage
3. Bell stage
4. Appositional stage (mineralization)
5. Root formation
6. Eruption
(epithelial ingrowth into ectomesenchyme)
(further epithelial growth)
(histo- and morpho-differentiation)
(formation of enamel and dentin of crown)
(formation of dentin and cementum of root)
ikassem@dr.com
104. Tooth eruption
1 mm
• Axial movement toward oral epithelium
begin when the root formation begin.
• Source of erupting force
: contraction of fibroblasts generating
periodontal ligaments?
ikassem@dr.com
105. Tooth eruption
reduced enamel ep.
osteoclasts
fused with oral ep.
form junctional ep.
Alveolar bone and connective tissue
are resorbed as teeth erupt.
ikassem@dr.com
107. Relationship of primary teeth and
succedaneous permanent teeth
s
open apex
resorption of rooterupting erupting
D : deciduous tooth
P or S : succedaneous tooth
ikassem@dr.com
108. Summary of tooth development
Oral epithelium
Dental lamina
ameloblastsInner enamel ep
Stellate reticulum
Stratum intermedium
Outer enamel ep HERS
Ectomesenchyme
Dental sac
Dental papilla odontoblasts
cementoblasts
fibroblasts
fibroblasts
osteoblasts
dentin
cementum
pulp
periodontal ligament
alveolar bone
enamel
guide root formation
oral epithelium
reduced enamel ep junctional ep.
ikassem@dr.com
109. Most odontogenic epithelial cells degenerate
following the completion of tooth formation
Oral epithelium
Dental lamina
ameloblastsInner enamel ep
Stellate reticulum
Stratum intermedium
Outer enamel ep HERS
Ectomesenchyme
Dental sac
Dental papilla odontoblasts
cementoblasts
fibroblasts
fibroblasts
osteoblasts
dentin
cementum
pulp
periodontal ligament
alveolar bone
enamel
guide root formation
oral epithelium
junctional ep.reduced enamel ep.
ikassem@dr.com
110. Molecular mechanism of tooth
development
Many genes control tooth development but not
completely understood
– shape, number of cusp (incisor vs molar)
– size
– number (2 vs 3 molars…..)
– location (mesio-distal, maxillo-mandibular….)
– timing of formation and eruption
Future of dentistry?
– Control the number and location of teeth
– In vitro formation of tooth
ikassem@dr.com
111. Most common craniofacial malformation
Cleft lip with or without cleft palate (CL/P)
or isolated cleft palate (CP).
CL/P and CP differ with respect to
– Embryology, etiology, candidate genes,
associated abnormalities, and recurrence risk.
ikassem@dr.com
114. Prevalence
CL/P is more common than CP and varies by
ethnicity.
CL/P
– High in American Indians and Asians (1/500
newborns)
– Low in American blacks (1/2000 newborns)
– Intermediate level in Caucasians (1/1000
newborns)
Isolated CP occurs in only 1/2500 newborns
and does not display variation by ethnicity.
ikassem@dr.com
115. Cleft Lip
Complete closure at 35 days
postconception:
– 7 weeks from the LMP.
– Lateral nasal, median nasal, and maxillary
mesodermal processes merge.
Failure of closure can produce unilateral,
bilateral, or median lip clefting.
Left side unilateral cleft is the most
common.
ikassem@dr.com
116. Cleft lip Severity
Mild, involving only the lip
Extend into the palate and midface
thereby affecting the nose, forehead,
eyes, and brain.
ikassem@dr.com
117. Cleft Palate
Lack of fusion of the palatal shelves.
Abnormalities in programmed cell death
may contribute to lack of palatal fusion(?).
Isolated disruption of palate shelves can
occur after closure of the lip
Palatal closure is not completed until 9
weeks post-conception.
ikassem@dr.com
118. Environmental agents
Several agents that are associated with an
increased frequency of midfacial
malformation.
Medications —phenytoin, sodium
valproate, methotrexate.
With corticosteroids there is no evidence
of an increase in malformations.
– Possible association could not be excluded
ikassem@dr.com
119. Prenatal Diagnosis
Diagnosed until the soft tissues of the
fetal face can be clearly visualized
sonographically (13 to 14 weeks).
The majority of infants with cleft lip also
have palatal involvement:
– 85% of bilateral cleft lips
– 70% associated with cleft palate.
– Cleft palate with an intact lip comprises 27%
of isolated CL/P
ikassem@dr.com
121. Syndrome ?
A thorough examination of the newborn or
stillbirth is always warranted.
Orofacial clefting is noted in over 300
syndromes.
3 deserve additional comment.
– frequency, variable presentations, and modes
of inheritance
ikassem@dr.com
122. Deletion of chromosome 22q11
DeGeorge syndrome.
Spectrum in addition to cleft palate:
– Conotruncal cardiac defects, thymic
hypoplasia, and velopharyngeal webs.
Majority of cases represent a new
microdeletion
In families with conotruncal malformations
and/or CP, further evaluation is
appropriate.
ikassem@dr.com
123. Oral-facial-digital syndrome, type I
X-linked dominant syndromes.
Manifestations in affected females are
variable and subtle:
– hyperplastic frenula
– cleft tongue
– cleft lip/palate
– digital anomalies
ikassem@dr.com
124. Treacher-Collins syndrome
Autosomal dominant disorder
Downward slanting palpebral fissures,
micrognathia, dysplastic ears, and
deafness.
– Mental development is normal.
The mutations appear to increase cell
death in the prefusion neural folds.
A family history with deafness, ear
abnormalities, or CP.
ikassem@dr.com
125. Obstetrical Management
Amniocentesis for karyotype should be
offered.
– high rate of chromosomal defects
Difficulty in prenatal sonographic diagnosis
supports chromosomal evaluation
As of January 2002, "in utero" correction
had been attempted only once in Mexico
– The child delivered prematurely and died at
two months of life
ikassem@dr.com
126. Feedings
Infants with CL/P have few feeding
problems.
If the cleft involves the hard palate, the
infant is usually not able to suck
efficiently.
– Experiment (special nipples or alternate
feeding positions)
The infant should be held in a nearly
sitting position during feeding
– Prevents flowing to the back into the nose.ikassem@dr.com
127. Feedings
It is important to
keep the cleft clean
Breastfeeding is
extremely
challenging.
ikassem@dr.com
128. Haberman Feeder
Activated by tongue and
gum pressure.
Milk cannot flow back.
Replenished continuously
as the baby feeds.
Prevents the baby from
being overwhelmed with
milk.
A gentle pumping action
to the body of the nipple
will increase flow.
ikassem@dr.com
129. More than 3,000 syndromes classified
Optimal growth, development, and learning requires
early recognition and intervention
Team Approach:
– Parents
– Pediatrician
– Otolaryngologist
– Cardiologist
– Nephrologist
– Geneticist
– Speech Therapist
– Teachers
– Others
The Sydromal
Child
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130. The Sydromal
Child
History
– Parental factors (age)
– Consanguinity
– Abortions
– Teratogen exposure
– Medical Pedigree
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131. Physical Exam
– Major and Minor Anomalies
Airway
Skull
Ears
Facial skeleton
– Comparison to Family Members
– Reference Material
The Sydromal
Child
ikassem@dr.com
133. Described by John Landon Down in
1866
Etiology: nondisjuction mutation
resulting in Trisomy 21
Prevalence 1:700
– Most common chromosomal anomaly
Associated with Maternal age > 35
Down
Syndrome
ikassem@dr.com
136. Airway Concerns
– Due to midface hypoplasia, the
nasopharynx and oropharynx dimensions
are smaller
Slight adenoid hypertrophy can cause upper
airway obstruction
– Congenital mild-moderate subglottic
narrowing not uncommon
Post-extubation stridor
Down
Syndrome
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137. Obstructive Sleep Apnea
– Prevalence 54-100% in DS patients
– Combination of anatomic and functional
mechanisms
Midface hypoplasia, macroglossia, etc
Hypotonia of pharyngeal muscles
Down
Syndrome
ikassem@dr.com
138. Obstructive Sleep Apnea
– Management:
Polysomnography to confirm
Medical interventions:
– CPAP
– Weight Loss
– Medications to stimulate respiratory drive
Down
Syndrome
ikassem@dr.com
143. TCS
First described by Thomson and Toynbee in
1846-7
– Later, essential components described by Treacher
Collins in 1960
Autosomal dominant inheritance
– TCOF1, mapped to 5q32-33.1
60% are from new mutation
– Associated with increased paternal age
Prevalence of 1 in 50,000
a.k.a. Mandibulofacial dysostosis
ikassem@dr.com
144. TCS
Characteristics
– Likely due to abnormal migration of neural crest cells into
first and second branchial arch structures
– Usually bilateral and symmetric
– Malar and supraorbital hypoplasia
– Non-fused zygomatic arches
– Cleft palate in 35%
– Hypoplastic paranasal sinuses
– Downward slanting palpebral fissures
– Mandibular hypoplasia with increased angulation
– Coloboma of lower eyelid with absent cilia
– Malformed pinna
– Normal intelligence
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145. TCS
OP/Airway concerns
– Cleft palate
– Choanal atresia may be present
Respiratory distress in newborn
Oral airway, McGovern nipple
– Obstructive sleep apnea is the most common
airway dysfunction
Mandibular hypoplasia results in retrodisplacement of
tongue into oropharynx
Oral airway, tracheotomy
Distraction osteogenesis vs. free fibular transfer
ikassem@dr.com
146. TCS
Otologic concerns
– Malpositioned auricles
– Malformed pinna
– EAC atresia
– Ossicular abnormalities
– Conductive hearing loss is common
Hearing aids are effective
– Normal intelligence
ikassem@dr.com
150. Apert and
Crouzon
Belong to family of Craniosynostoses
Apert Syndrome (Acrocephalosyndactyly)
– First described by Wheaton in 1894
– Apert further expanded in 1906
Crouzon Syndrome (Craniofacial Dysostosis)
– Described by Crouzon in 1912
Autosomal dominant inheritance
– Most are sporadic in Apert Syndrome
– 1/3 are sporadic in Crouzon Sydrome
Prevalence: 15 - 16 per 1,000,000
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151. Apert and
Crouzon
Typical characteristics
– Craniosynostosis
Coronal sutures fused at birth
Larger than average head circumference at
birth
– Midfacial malformation and hypoplasia
– Shallow orbits with exophthalmos
– Apert Syndrome: symmetric syndactyly of
hands and feet
ikassem@dr.com
152. Apert and
Crouzon
Crouzon and Apert Syndromes facial
features
– Shallow orbits with exophthalmos
– Retruded midface with relative
prognathism
– Beaked nose
– Hypertelorism
– Downward slanting palpebral fissures
ikassem@dr.com
156. PRS
Triad of micrognathia, glossoptosis and cleft
palate
– First described by St. Hilaire in 1822
– Pierre Robin first recognized the association of
micrognathia and glossoptosis in 1923
Prevalence: 1 of every 8,500 newborns
– Syndromic 80%
Treacher Collins Syndrome
Velocardiofacial Syndrome
Fetal Alcohol Syndrome
– Nonsyndromic 20%
ikassem@dr.com
157. PRS
Mandibular Deficiency
Hypoplastic and
Retruded Mandible
(Micrognathia)
Tongue Remains
Retruded and High in
Oropharynx
(Glossoptosis)
Failure of Fusion of
Lateral Palatal Shelves
Cleft Palate
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