Craniofacial Defects

Question 1

What are some examples of 1st arch disorders?

Answer 1

Treacher Collins Syndrome

Pierre Robin Syndrome

Question 2

What are some examples of 3rd/4th arch disorders?

Answer 2

DiGeorge Syndrome

Velocardiofacial Syndrome

Question 3

What causes Treacher Collins Syndrome?

Answer 3

Malformations in 1st and 2nd pharyngeal arch derivaties; lack of neural crest migration/population

Question 4

What is the candidate gene of Treacher Collins Syndrome?

Answer 4

Tcof1 a transcription factor gene found on chromosome 5

Question 5

What are the symptoms of trencher-collins syndrome?

Answer 5

Malformation of faces, skull, eyes, ears, nose and palate
Narrow face, hypo plastic supraorbital rims & zygotes
Sunken cheekbones
Malformed pinnae
Receding chin & downturned mouth

Question 6

What are the clinical features of Pierre Robin Syndrome/Sequence?

Answer 6

Hypoplasia of mandible prior to wk 9
Posterior position of tongue prevents overgrowth of posterior palatal shelves
Unusual rounded cleft
Posterior airway obstruction

Question 7

What are the clinical features of DiGeorge Syndrome?

Answer 7

Absence of thymus &/or parathyroids
Micrognathia
Hypertelorism
Low set, posteriorly angulated ears
Short philtrum
Choanal atresia

Question 8

How is DiGeorge Syndrome inherited?

Answer 8

AR, AD, sporadic

Also can be induced by teratogens

Question 9

What is the cause of DiGeorge Syndrome?

Answer 9

Lack of neural crest cell migration into 3rd & 4th pharyngeal pouches

Question 10

What are the candidate genes of DiGeorge Syndrome?

Answer 10

Tbx1 & TUPLE

Embryonic transcription factor genes found on chromosome 22

Question 11

What disorder causes Velocardiofacial syndrome?

Answer 11

22q11 monosomy

Question 12

What are symptoms of Velocardiofacial syndrome similar to?

Answer 12

Severe forms of DiGeorge Syndrome

Question 13

What are the symptoms of Velocardiofacial syndrome?

Answer 13

Cardiac
Abnormal faces
Thymic hypoplasia
Cleft palate
Hypocalcemia

Question 14

What’s the incidence of Velocardiofacial syndrome?

Answer 14

1:2000

Question 15

What causes cleft lip?

Answer 15

Failure of maxillary prominence to fuse with medial nasal prominence

Question 16

What causes cleft palate?

Answer 16

Failure of the palatine shelved to fuse

Question 17

What is anterior cleft palate?

Answer 17

No fusion with primary palate

Question 18

What is posterior cleft palate?

Answer 18

No fusion with nasal septum

Question 19

What is the cleft palate/lip incidence in the Japanese, Caucasians and American Blacks?

Answer 19

Japanese - 1.7:1000
Caucasian - 1:1000
American Blacks - 0.4:1000

Question 20

What are the risk factors for cleft lip/palate?

Answer 20

Smoking
Alcohol
Retinoic Acid
Dilantin

Question 21

What is a thyroglossal duct cyst?

Answer 21

Persistence of the thyroglossal duct which results in cyst formation at the base of the throat

Question 22

What is Ankyloglossia or ‘Tongue Tie’?

Answer 22

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

Question 23

What is a pharyngeal fistula?

Answer 23

Pharyngeal pouch 2 & pharyngeal groove 2 persist; forms opening from internal tonsilar area to external neck

Question 24

What is a pharyngeal cyst?

Answer 24

Pharyngeal groove persists, usually near angle of mandible

Question 25

What is ectopic, parathyroid/thyroid?

Answer 25

Abnormal migration of gland tissue from embryonic origin

Question 26

What are some features of Amelogenesis Imperfecta: AlH1: Hypoplastic?

Answer 26

``` Male - thin enamel Female - regions of thick and thin enamel AmelX mutation Amelogenin defect X-linked inheritance ```

Question 27

What are some features of Amelogenesis Imperfecta: AlH2: Hypomineralization?

Answer 27

Enamel is of normal thickness but is extremely soft AMBN mutation? Ameloblastin defect? AD inheritance

Question 28

What are the clinical features of dentinogenesis imperfecta?

Answer 28

Opalescent blue-gray Bulbous crowns, narrow roots, small pulp chambers & root canals Enamel splits easily

Question 29

What mutation causes Dentinogenesis Imperfecta?

Answer 29

Dspp mutation (dentin phosphoprotein & dentin sialoprotein)

Question 30

What is craniosynostosis?

Answer 30

Premature fusion of the cranial sutures

Question 31

What are some examples of syndromic craniosynostosis?

Answer 31

Pfeiffer Apert/Crouzan Saethre-Chotzen Greig-Cephalopolysyndactyly

Question 32

What are some non-syndromic examples of craniosynostosis?

Answer 32

Compression associated Examples include multiple fetuses Uterine malformation

Question 33

What are most FGFR mutations clustered around?

Answer 33

The Ig domain 3

Question 34

What do FGFR mutations that cause craniocynostosis result in?

Answer 34

"gain of function" due to self-dimerization

Question 35

What does a defect in fgfr1 cause?

Answer 35

Pfeiffer syndrome

Question 36

What does a defect in fgfr2 cause?

Answer 36

Apert Syndrome | Crouzan Syndrome

Question 37

What does a defect in fgfr3 cause?

Answer 37

Achondroplasia | Craniosynostosis

Question 38

What does a defect in twist cause?

Answer 38

Saethre-Chotzen

Question 39

What does a defect in gli3 cause?

Answer 39

Greig Cephalopolysyndactyly

Question 40

What are some clinical features of apert syndrome?

Answer 40

``` AD inheritance Osseous syndactyly Coronal craniosynostosis Mental deficiency +/- cleft palate fgfr2 mutation ```

Question 41

What are some clinical features of Saethre-Chotzen Syndrome?

Answer 41

``` AD inheritance Coronal craniosynostosis Maxillary hypoplasia Facial assymetry Hyperteloricm Cutaneous syndactyly Twist mutation ```

Question 42

What is holoprosencephaly?

Answer 42

A developmental field defect of impaired midline cleavage of the embryonic forebrain

Question 43

What are some causes of Holoprosencephaly?

Answer 43

15-20% genetic causes Teratogens Maternal diabetes mellitus Maternal hypocholesterolemia

Question 44

What signaling protein is often found to be defective in many forms of holoprosencephaly?

Answer 44

shh or sonic hedgehog protein

Question 45

What 3 other proteins are involved in the holoprosencephaly pathway?

Answer 45

patched: Shh receptor (ligand binding) smoothened: Shh receptor (signaling) gli: transcription factor