Craniofacial Defects Flashcards
What are some examples of 1st arch disorders?
Treacher Collins Syndrome
Pierre Robin Syndrome
What are some examples of 3rd/4th arch disorders?
DiGeorge Syndrome
Velocardiofacial Syndrome
What causes Treacher Collins Syndrome?
Malformations in 1st and 2nd pharyngeal arch derivaties; lack of neural crest migration/population
What is the candidate gene of Treacher Collins Syndrome?
Tcof1 a transcription factor gene found on chromosome 5
What are the symptoms of trencher-collins syndrome?
Malformation of faces, skull, eyes, ears, nose and palate
Narrow face, hypo plastic supraorbital rims & zygotes
Sunken cheekbones
Malformed pinnae
Receding chin & downturned mouth
What are the clinical features of Pierre Robin Syndrome/Sequence?
Hypoplasia of mandible prior to wk 9
Posterior position of tongue prevents overgrowth of posterior palatal shelves
Unusual rounded cleft
Posterior airway obstruction
What are the clinical features of DiGeorge Syndrome?
Absence of thymus &/or parathyroids Micrognathia Hypertelorism Low set, posteriorly angulated ears Short philtrum 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 neural crest cell migration into 3rd & 4th pharyngeal pouches
What are the candidate genes of DiGeorge Syndrome?
Tbx1 & TUPLE
Embryonic transcription factor genes found on chromosome 22
What disorder causes Velocardiofacial syndrome?
22q11 monosomy
What are symptoms of Velocardiofacial syndrome similar to?
Severe forms of DiGeorge Syndrome
What are the symptoms of Velocardiofacial syndrome?
Cardiac Abnormal faces Thymic hypoplasia Cleft palate Hypocalcemia
What’s the incidence of Velocardiofacial syndrome?
1:2000
What causes cleft lip?
Failure of maxillary prominence to fuse with medial nasal prominence
What causes cleft palate?
Failure of the palatine shelved to fuse
What is anterior cleft palate?
No fusion with primary palate
What is posterior cleft palate?
No fusion with nasal septum
What is the cleft palate/lip incidence in the Japanese, Caucasians and American Blacks?
Japanese - 1.7:1000
Caucasian - 1:1000
American Blacks - 0.4:1000
What are the risk factors for cleft lip/palate?
Smoking
Alcohol
Retinoic Acid
Dilantin
What is a thyroglossal duct cyst?
Persistence of the thyroglossal duct which results in cyst formation at the base of the throat
What is Ankyloglossia or ‘Tongue Tie’?
Caused by frenulum that extends too far anteriorly, limiting movement of the tongue
What is a pharyngeal fistula?
Pharyngeal pouch 2 & pharyngeal groove 2 persist; forms opening from internal tonsilar area to external neck
What is a pharyngeal cyst?
Pharyngeal groove persists, usually near angle of mandible
What is ectopic, parathyroid/thyroid?
Abnormal migration of gland tissue from embryonic origin
What are some features of Amelogenesis Imperfecta: AlH1: Hypoplastic?
Male - thin enamel Female - regions of thick and thin enamel AmelX mutation Amelogenin defect X-linked inheritance
What are some features of Amelogenesis Imperfecta: AlH2: Hypomineralization?
Enamel is of normal thickness but is extremely soft
AMBN mutation?
Ameloblastin defect?
AD inheritance
What are the clinical features of dentinogenesis imperfecta?
Opalescent blue-gray
Bulbous crowns, narrow roots, small pulp chambers & root canals
Enamel splits easily
What mutation causes Dentinogenesis Imperfecta?
Dspp mutation (dentin phosphoprotein & dentin sialoprotein)
What is craniosynostosis?
Premature fusion of the cranial sutures
What are some examples of syndromic craniosynostosis?
Pfeiffer
Apert/Crouzan
Saethre-Chotzen
Greig-Cephalopolysyndactyly
What are some non-syndromic examples of craniosynostosis?
Compression associated
Examples include multiple fetuses
Uterine malformation
What are most FGFR mutations clustered around?
The Ig domain 3
What do FGFR mutations that cause craniocynostosis result in?
“gain of function” due to self-dimerization
What does a defect in fgfr1 cause?
Pfeiffer syndrome
What does a defect in fgfr2 cause?
Apert Syndrome
Crouzan Syndrome
What does a defect in fgfr3 cause?
Achondroplasia
Craniosynostosis
What does a defect in twist cause?
Saethre-Chotzen
What does a defect in gli3 cause?
Greig Cephalopolysyndactyly
What are some clinical features of apert syndrome?
AD inheritance Osseous syndactyly Coronal craniosynostosis Mental deficiency \+/- cleft palate fgfr2 mutation
What are some clinical features of Saethre-Chotzen Syndrome?
AD inheritance Coronal craniosynostosis Maxillary hypoplasia Facial assymetry Hyperteloricm Cutaneous syndactyly Twist mutation
What is holoprosencephaly?
A developmental field defect of impaired midline cleavage of the embryonic forebrain
What are some causes of Holoprosencephaly?
15-20% genetic causes
Teratogens
Maternal diabetes mellitus
Maternal hypocholesterolemia
What signaling protein is often found to be defective in many forms of holoprosencephaly?
shh or sonic hedgehog protein
What 3 other proteins are involved in the holoprosencephaly pathway?
patched: Shh receptor (ligand binding)
smoothened: Shh receptor (signaling)
gli: transcription factor
