Craniogacial Dysmorphologies Flashcards by Nargis Barkzai

What are 1st pharyngeal arch disorders:

Treacher Collins Syndrome

2. Pierre Robin Syndrome

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What are 3/4th pharyngeal arch disorders

digeorge syndrome

2. velocardiofacial syndrome

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how do you get treacher collins syndrome

malformations in 1st and 2nd pharyngeal arch derivatives; lack of nerual crest migration/population

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what is the candidate gene for Treacher collins syndrome

Tcof1; transcription factor gene found on chromosome 5

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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

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what is coloboma

notch on eyelid that can be in iris or other structures of eye

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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!

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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

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How is DiGeorge syndrome inherited

AR, AD, sporadic; also can be induced by teratogens

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What is the cause of DiGeorge Syndrome

lack of nerual crest cell migration into 3rd and 4th pharyngeal pouches.

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what are candidate genes for digeorge syndrome

Tbx1 and TUPLE- embryonic transcription factor genes found on chromosome 22.

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Velocardiofacial syndrome is a ___monosomy

22q11 (deletion); similar to Digeorge

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What does CATCH 22 stand for in velocardiofacial syndrome

C: cardiac
A: abnormal facies
T: thymic hypoplasia
C: cleft palate
H: hypocalcemia

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Cleft lip results from failure of ____ prominence to fuse with medial ____ prominence

maxillary; nasal

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Cleft palate is caused by failure of the ____ ___ to fuse

palatine shelves

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Which ethnic group is most affected by cleft lip/palate

japanese

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what are risk factors for cleft/lip palate

smoking
alcohol
retinoic acid
dilantin

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what is thyroglossal duct cyst

persistence of the thryoglossal duct results in cyst formation at the base of the throat

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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

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 ____

dimerize

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 - AR - 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

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

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