Craniogacial Dysmorphologies

Question 1

What are 1st pharyngeal arch disorders:

Answer 1

1. Treacher Collins Syndrome

2. Pierre Robin Syndrome

Question 2

What are 3/4th pharyngeal arch disorders

Answer 2

1. digeorge syndrome

2. velocardiofacial syndrome

Question 3

how do you get treacher collins syndrome

Answer 3

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

Question 4

what is the candidate gene for Treacher collins syndrome

Answer 4

Tcof1; transcription factor gene found on chromosome 5

Question 5

what are features of TC syndrome

Answer 5

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

Question 6

what is coloboma

Answer 6

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

Question 7

how do you get pierre robin syndrome

Answer 7

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!

Question 8

what are features of DiGeorge syndrome

Answer 8

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

Question 9

How is DiGeorge syndrome inherited

Answer 9

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

Question 10

What is the cause of DiGeorge Syndrome

Answer 10

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

Question 11

what are candidate genes for digeorge syndrome

Answer 11

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

Question 12

Velocardiofacial syndrome is a ___monosomy

Answer 12

22q11 (deletion); similar to Digeorge

Question 13

What does CATCH 22 stand for in velocardiofacial syndrome

Answer 13

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

Question 14

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

Answer 14

maxillary; nasal

Question 15

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

Answer 15

palatine shelves

Question 16

Which ethnic group is most affected by cleft lip/palate

Answer 16

japanese

Question 17

what are risk factors for cleft/lip palate

Answer 17

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

Question 18

what is thyroglossal duct cyst

Answer 18

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

Question 19

what is ankyloglossia/tongue tie

Answer 19

caused by frenulum that extends too far anteriorly, limiting movement of the tongue

Question 20

what is pharyngeal fistula

Answer 20

pharyngeal pouch 2 and pharyngeal grove 2 persist; forms opening from internal tonsilar area to external neck

Question 21

what is pharyngeal cyst

Answer 21

pharyngeal grooves persist, usually near angle of mandible

Question 22

what is ectopic thyms

Answer 22

abnormal migration of gland tissue from embryonic origin

Question 23

what are features of A1H1 Hypoplastic

Answer 23

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

Question 24

what are features of A1H2: hypomineralized

Answer 24

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

Question 25

what is dentinogenesis imperfecta

Answer 25

blue/gray coloration of teeth. Enamel flakes away and splits off easily. -Caused by Dspp mutation

Question 26

what is most disabling to the process of embryogeniss

Answer 26

1. Growth factors (FGF) 2. Growth factor receptors (SHH) 3. transcription factors (Gli3, TWIST)

Question 27

what is craniosynostosis

Answer 27

premature fusion of the cranial structures; changes shape of head

Question 28

what are some shapes of premature fusion of cranial sutures

Answer 28

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

Question 29

what are types of syndromic craniosynostosis:

Answer 29

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

Question 30

what are non syndromic types of craniosynostosis

Answer 30

can be induced mechanically; compression associated due to: - multiple fetuses - uterine malformation: fetus grows on one side

Question 31

How many FGF genes are there? what is it for?

Answer 31

22; FGF signaling alters levels of many TF's impt in dev of bone, cartilage and teeth.

Question 32

Most FGFR mutations are clustered around

Answer 32

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)

Question 33

FGFR mutations that cause craniosynostosis result in ___ type of mutation due to self dimerization.

Answer 33

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)

Question 34

fgfr3 gene causes ___ | twist gene causes ____

Answer 34

achondroplasia (dwarfism) | saethre-chotzen (TF act by FGFR signaling)

Question 35

If proline convertts to argenine it causes receptor to ____

Answer 35

dimerize

Question 36

what is Apert syndrome

Answer 36

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

Question 37

What are features of Saethre chotzen syndrome

Answer 37

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

Question 38

what is holoprosencephaly

Answer 38

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

Question 39

Heterogenous causes and pathology of holoprosencephaly

Answer 39

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

Question 40

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

Answer 40

SHH

Question 41

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

Answer 41

ligand; signaling; gli3

Question 42

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

Answer 42

signaling

Question 43

what are the SHH domains

Answer 43

Signaling domain | autocatalytic cleavage and cholesterol transferase domains

Question 44

why does SHH need cholesterol

Answer 44

SHH req cholesterol binding in order to be rec by its receptor. Transfers cholesterol and cleaves itself off which is active form of SHH

Question 45

what is SHH signaling pathway

Answer 45

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

Question 46

no hypothalamus:

Answer 46

no thyroud funciton no rep function diabetes insipidis