Craniogacial Dysmorphologies Flashcards
What are 1st pharyngeal arch disorders:
- Treacher Collins Syndrome
2. Pierre Robin Syndrome
What are 3/4th pharyngeal arch disorders
- digeorge syndrome
2. velocardiofacial syndrome
how do you get treacher collins syndrome
- malformations in 1st and 2nd pharyngeal arch derivatives; lack of nerual crest migration/population
what is the candidate gene for Treacher collins syndrome
Tcof1; transcription factor gene found on chromosome 5
what are features of TC syndrome
- malformation of facies, skull, eyes, ears nose and palate
- narrow face, hypoplastic supraorbital rims and zygomas
- sunken cheekbones
- malformed pinnae
- receding chin and downturned mouth
what is coloboma
notch on eyelid that can be in iris or other structures of eye
how do you get pierre robin syndrome
hypoplasia of mandible prior to week 9:
position of fetus in utero causes a constriction in the way the chin is pressed up against chest causesand backwards placement of tongue. the tongue cant get away in time for PS to flip up and fuse.
end up with cleft and hypoplatic jaw which keeps tongue placed backwardly which causes problems with respiration. Have short mandible. This corrects itself after birth. This is mechanical not genetic!
what are features of DiGeorge syndrome
- absence of thymus (immune system) and paraythyroids (calcium met)
- micrognathia: small jaw
- hypertelorism: wide set eyes
- low set, posteriorly angulated ears
- short philtrum: fish mouth deformity
- choanal atresia
How is DiGeorge syndrome inherited
AR, AD, sporadic; also can be induced by teratogens
What is the cause of DiGeorge Syndrome
lack of nerual crest cell migration into 3rd and 4th pharyngeal pouches.
what are candidate genes for digeorge syndrome
- Tbx1 and TUPLE- embryonic transcription factor genes found on chromosome 22.
Velocardiofacial syndrome is a ___monosomy
22q11 (deletion); similar to Digeorge
What does CATCH 22 stand for in velocardiofacial syndrome
C: cardiac A: abnormal facies T: thymic hypoplasia C: cleft palate H: hypocalcemia
Cleft lip results from failure of ____ prominence to fuse with medial ____ prominence
maxillary; nasal
Cleft palate is caused by failure of the ____ ___ to fuse
palatine shelves
Which ethnic group is most affected by cleft lip/palate
japanese
what are risk factors for cleft/lip palate
- smoking
- alcohol
- retinoic acid
- dilantin
what is thyroglossal duct cyst
persistence of the thryoglossal duct results in cyst formation at the base of the throat
what is ankyloglossia/tongue tie
caused by frenulum that extends too far anteriorly, limiting movement of the tongue
what is pharyngeal fistula
pharyngeal pouch 2 and pharyngeal grove 2 persist; forms opening from internal tonsilar area to external neck
what is pharyngeal cyst
pharyngeal grooves persist, usually near angle of mandible
what is ectopic thyms
abnormal migration of gland tissue from embryonic origin
what are features of A1H1 Hypoplastic
- thin enamel overall in males
- regions of thick and thin enamel in female
- AmelX mutation
- Amelogenin defect
- X linked inheritance
what are features of A1H2: hypomineralized
- Ameloblastin defect
- Enamel is of normal thickness bt is extremely soft
- AD inheritance
what is dentinogenesis imperfecta
blue/gray coloration of teeth. Enamel flakes away and splits off easily.
-Caused by Dspp mutation
what is most disabling to the process of embryogeniss
- Growth factors (FGF)
- Growth factor receptors (SHH)
- transcription factors (Gli3, TWIST)
what is craniosynostosis
premature fusion of the cranial structures; changes shape of head
what are some shapes of premature fusion of cranial sutures
- metopic: pointy
2. coronal: growth out in 1 direction
what are types of syndromic craniosynostosis:
- Pheiffer: clover like head
- apert/crouzon
- saethre-chotzen
- greig cephalopolysyndactly
what are non syndromic types of craniosynostosis
can be induced mechanically; compression associated due to:
- multiple fetuses
- uterine malformation: fetus grows on one side
How many FGF genes are there? what is it for?
22; FGF signaling alters levels of many TF’s impt in dev of bone, cartilage and teeth.
Most FGFR mutations are clustered around
Ig domain 3; gain of function type of mutaiton; dimerize on their own w/o FGF around; send PKC act signal for cytoskeletal org, also inhibits apoptosis, aso causes proliferation (MAPK signaling)
FGFR mutations that cause craniosynostosis result in ___ type of mutation due to self dimerization.
gain of function type of mutaiton; dimerize on their own w/o FGF around; send PKC act signal for cytoskeletal org, also inhibits apoptosis for suture formation, also causes proliferation (MAPK signaling)
fgfr3 gene causes ___
twist gene causes ____
achondroplasia (dwarfism)
saethre-chotzen (TF act by FGFR signaling)
If proline convertts to argenine it causes receptor to ____
dimerize
what is Apert syndrome
fgfr2 mutation:
- AD inheritance
- osseous syndactyly
- coronal craniosynostosis
- mental deficiency
- +/- cleft palate
What are features of Saethre chotzen syndrome
- AD inheritance
- coronal cranio synostosis
- maxillary hypoplasia
- facial assymetry
- hypertelorism
- cutaneous syndactyly
what is holoprosencephaly
a dev field defect of impaired midline cleavage of the embryonic forebrain.
Heterogenous causes and pathology of holoprosencephaly
- 15-20% genetic causes: SHH signalers:
- AD w wide expressivity and incomplete penetrance
- AR
- X linked - Teratogens: alcohol, RA
- Maternal DM
- maternal hypocholesterlomeia: too little cholesterol
____ is a signaling protein found to be defective in many forms of holoprosencephaly
SHH
Other proteins in the pathway include: patched which is a SHH receptor for ____binding, smoothened whch is SHH receptor for ____ and ____ which is a TF
ligand; signaling; gli3
SHH has a ____ peptide which sends it to the ER and will be cleaved off by signaling peptidase which makes it go to ER and Golgi and gets secreted. Also has two major domains
signaling
what are the SHH domains
Signaling domain
autocatalytic cleavage and cholesterol transferase domains
why does SHH need cholesterol
SHH req cholesterol binding in order to be rec by its receptor. Transfers cholesterol and cleaves itself off which is active form of SHH
what is SHH signaling pathway
- binds to patched which then
- activates smoothened (actual signaling component) which then activates
- Gli TF
- ACtivates other growth factors and more of its own receptor
no hypothalamus:
no thyroud funciton
no rep function
diabetes insipidis
