Craniogacial Dysmorphologies Flashcards Preview

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Flashcards in Craniogacial Dysmorphologies Deck (46):

What are 1st pharyngeal arch disorders:

1. Treacher Collins Syndrome
2. Pierre Robin Syndrome


What are 3/4th pharyngeal arch disorders

1. digeorge syndrome
2. velocardiofacial syndrome


how do you get treacher collins syndrome

1. 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

1. malformation of facies, skull, eyes, ears nose and palate
2. narrow face, hypoplastic supraorbital rims and zygomas
3. sunken cheekbones
4. malformed pinnae
5. 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

1. absence of thymus (immune system) and paraythyroids (calcium met)
2. micrognathia: small jaw
3. hypertelorism: wide set eyes
4. low set, posteriorly angulated ears
5. short philtrum: fish mouth deformity
6. 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

1. 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



what are risk factors for cleft/lip palate

1. smoking
2. alcohol
3. retinoic acid
4. 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

1. thin enamel overall in males
2. regions of thick and thin enamel in female
3. AmelX mutation
4. Amelogenin defect
5. X linked inheritance


what are features of A1H2: hypomineralized

1. Ameloblastin defect
2. Enamel is of normal thickness bt is extremely soft
3. 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

1. Growth factors (FGF)
2. Growth factor receptors (SHH)
3. 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

1. metopic: pointy
2. coronal: growth out in 1 direction


what are types of syndromic craniosynostosis:

1. Pheiffer: clover like head
2. apert/crouzon
3. saethre-chotzen
4. 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 ____



what is Apert syndrome

fgfr2 mutation:
1. AD inheritance
2. osseous syndactyly
3. coronal craniosynostosis
4. mental deficiency
5. +/- cleft palate


What are features of Saethre chotzen syndrome

1. AD inheritance
2. coronal cranio synostosis
3. maxillary hypoplasia
4. facial assymetry
5. hypertelorism
6. cutaneous syndactyly


what is holoprosencephaly

a dev field defect of impaired midline cleavage of the embryonic forebrain.


Heterogenous causes and pathology of holoprosencephaly

1. 15-20% genetic causes: SHH signalers:
-AD w wide expressivity and incomplete penetrance
-X linked

2. Teratogens: alcohol, RA
3. Maternal DM
4. maternal hypocholesterlomeia: too little cholesterol


____ is a signaling protein found to be defective in many forms of holoprosencephaly



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



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

1. binds to patched which then
2. activates smoothened (actual signaling component) which then activates
3. Gli TF
4. ACtivates other growth factors and more of its own receptor


no hypothalamus:

no thyroud funciton
no rep function
diabetes insipidis