1. Craniofacial development Flashcards
Proportion of babies with craniofacial defects
1/700
Holoprosencephaly results in
(4)
- Nasal proboscis
- Failure of telencephalon to bifurcate
- Loss of nasal Septum
- Cyclopoeia
What defect?

Holoprosencephaly
Causes of Holoprosencephaly in live births
(5)
- Congenital ~25%, otherwise environmental
- Diabetic Mothers
- Alcohol
- Aspirin
- 3rd week infection with virus (siphilis, rubella, herpes)
Causes of Holoprosencephaly in embryo
3
- 45% trisomy (X18 or X13)
- Cyclopamine as SHH antagonist on PITCH1 receptor
- Mutation of DISP1, SHH, PTCH1,GLI1
DISP1 activates
Sonic Hedgehog is activated by
Sonic Hedgehog agonises
PTCH1
GLI1 is a transcription factor activated by
PTCH, a surface receptor
- The major cause of mental retardation in the western world
- I/500 live births
Foetal alcohol syndrome
Foetal alcohol syndrome involves
5
- Thin upper lip
- Rounded, indistinct philtrum
- Small Palpebral fissures
- Epicanthal folds on upper eyelid
- microcephaly and micrognathia
Palpebral fissures
eyelids
Philtrum
bifid structure between the septum and the lips

A. neurocranium
B. Chondrocranium
C. Viscerocranium
- Auditory ossicles (maleus, incus, stapes)
- Lambdoid stuture
- Alisphenoid
- Occipital Squama
- Coronal Stuture
- Posterior Fontanelle
Neurocranium includes
- Frontal
- Parietal
Intermembranous ossification
Viscerocranium
- Maxilla
- Mandible
- Ear Ossicles
- Styloid Process
- Hyoid
- Laryngeal cartilages
Chondrocranium includes
- Ethmoid
- Sphenoid
- Occipital
Endochondrial ossification
Bone fomation process?

- Endochondrial
- Intramembranous
Craniosynostis, common types
2
- Sagittal 40%
- Coronal15%
Which malformation?
3

- Apert
- Crouzon
- Pfeiffer
- Congenital craniostynosis syndrome cases / all craniostynosis =
~30%
Congenital Craniostynosis syndromes and FGFR receptor mutations.
4
- Muenke FGFR3
- Apert FGFR2
- Crouzon FGFR3 & FGFR2
- Pfeiffer FGFR1 & FGFR2
FGFR mutations
- Are dominant
- Overly high affinity for FGF
- Early ossification of intramembranous stuture
Ectoderm -> Cleft
Endoderm -> ?
Ectoderm -> Pouch
Endoderm -> ?
Ectoderm -> Pouch
Endoderm -> ?
Ectoderm -> Cleft
Endoderm -> ?
Cranial Neural crest: What parts?

- Midbrain
- Forebrain
- Frontonasal Process
- Pharyngeal arches
- Otic Vesicle (inner ear)
1st Pharyngeal arch: which origins?

- Paraxial Mesoderm
- Cranial Neural Crest cells
Neural crest contributes to
6
- Neurons and glia of the brain - which?
- Bones of Neurocranium, Chondrocranium and viscerocranium
- Tooth odontoblasts
- Facial connective tissue
- Pulmonary trunk
- Septation of aorta
Pharyngeal arches

- Frontonasal process
- Maxilliary process
- Hyoid Process
- Mandibular process
- 24 days
Facial Development

- frontonasal process
- Medial nasal plactode (of fnp)
- lateral nasal plactode (of fnp)
- Maxilliary prominences
- Mandibular prominences
- Intermaxilliary process
- bridge of nose and philtrum
a = 6
b = 7
c = 10
bifid nose
result of the incomplete fusion of the medial nasal prominences
- orbital hypertelorism
- notched nasal tip or divided nostrils
- deficit in midline frontal bone
orbital hypertelorism
eyes are too far apart
Cleft lips
- Incidence
- Reason
- Varieties and proportion
- Association with cleft palate
- 1/1000
- Failure of maxilliary swellings to fuse with intermaxilliary process. Cause of this unclear
- Unilateral 90%, Bilateral 10%
- 50% concur with cleft palate.
Palate formation

- Primary Palate
- Palatine shelves
- Maxilliary Prominences
- Nasal septum
- Nasal Chambers
- Tongue
Primary palate
Formed by an extension of the intermaxilliary process, fusing with the palatine shelves
Palatine shelves
Grow medially from the maxilliary prominences
Initially grow beneath the tounge, then rise to meet at the midline above along with the nasal septum.
Nasal septum
Separates the left and right nasal chambers
Hard Palate
Formed by the endochondrial ossification of the lower half of the palate
Cleft palate
- Incidence
- Association with cleft lip
- Causes (3)
- 1/2000
- 50%
- inadequate growth of palatine shelves
- palatine shelves fail to elevate above the tongue
- head excessively wide
Palate fusion
Occurrs during week 7-10
Fate of pharyngeal Cartilages
Arch 1
3
- Alisphenoid
- Malleus
- Incus
Fate of pharyngeal Cartilages
Arch 2
4
- Stapes
- Styloid Process
- Stylohyoid ligament
- Lesser Cornu of Hyoid
Fate of pharyngeal Cartilages
Arch 3
2
- Body of hyoid
- Greater cornu of hyoid
Fate of pharyngeal Cartilages
Arch 4
2
- Thyroid cartilage
- Cricoid Cartilage
Fate of pharyngeal muscles
Arch 1
4
- Temporalis
- Masseter
- Mylohyoid
- Anterior Belly of digastric
Fate of pharyngeal muscles
Arch 2
6
- Temporalis
- Orbicularis Oculi
- Orbicularis Oris
- Auricularis
- Masseter
- Posterior Belly of digastric
Fate of pharyngeal muscles
Arch 3
1
- Stylopharyngeus
Fate of pharyngeal muscles
Arch 4
- Middle Constrictor of Larynx
- Inferior constrictor of Larynx
- Cricothyroid muscles
Pharyngeal Cleft fates
4
- External Auditory Meatus
- Enclosed by outgrowth of 2nd arch
- Enclosed by outgrowth of 2nd arch
- Enclosed by outgrowth of 2nd arch
Pinna
Fromed from six auricular hillocks
Three from first and three from second pharyngeal arches
Pharyngeal Pouches’ fate
Endoderm patterns the identity of each pouch.
- Internal Auditory tube and primary tympanic recess
- Palatine tonsil
- Inferior Parathyroid gland and thymus
- Superior Parathyroid gland and ultimobranchial bofy
Thryroid is made from
Endoderm at the base of the pharynx
Treacher Collins Syndrome
- Incidence
- Reasons
- Features (5)
- 1/50,000 births
- Growth in 1st & 2nd Pharyngeal arches is limited
- .
- Hypoplasia of the mandible, zygomatics, outer and middle ear
- Downward slant of palpebral fissures
- Notching of the lower eyelids
- Paucity of eyelashes
- High Palate, usually cleft
Treacher collins incidence
Inheritance : New Mutations
4:6
Treacher Collins
- Trait type
- gene
- Gene’s protein function (3)
- Autosomal Dominant: penetrance variable; 60% of cases the result of new mutations.
- Caused by various mutstions in TCOF1, a gene which codes the protein “treacle”
- Treacle is involved in ribosomal biogenesis
- Strongly expressed in the neural folds and pharyngeal arches of embryos
- With defective treacle, cranial neural crest sees reduced mitosis and increased apoptosis.
- Therefore facial defects occurr due to a lack of material.