S2 - Craniofacial Malformations & Cleft Lip and Palate Flashcards
What are the different stages of embryonic craniofacial development? Which syndromes are associated with each stage and 3 categories?
1) Germ layer formation - FAS
2) Neural tube formation - Anencephaly
3) Migration of neural crest cells - Hemifacial microsomia, Treacher Collins syndrome
4) Organ system formation - Cleft Lip
4a) Primary palate - Cleft Palate
4b) Secondary palate
5) Final differentiation of tissues - Crouzon’s Syndrome (craniosynostosis), Achrondoplasia
1-3 are neural crest problems (day 17-28), 4 is lack of fusion (week 4-8) , 5 is suture problems (day 50-birth)
What is a teratogen. What are some examples and their result?
substance which interferes w normal development
Aspirin, cigarette smoke, Dilantin (phenytoin) → Cleft lip/palate
Zika virus, x-radiation → microcephaly
Others: ethyl alcohol, Rubella, Valium (diazepam), excess Vit D, Thalidomide
Name Neural Crest problems
FAS, Treacher Collins Syndrome, Hemifacial (craniofacial) microsomia, Anencephaly
Which stage of embyronic development would alcohol cause FAS
germ layer formation (17 days)
What is FAS caused by
exposure to alcohol (maternal use) during early development
causes preventable alcohol related birth defects - craniofacial malformation in early pregnancy, impaired cognitive and behavioural development in late stage pregnancy
→ microcephaly (small head), smooth philtrum, thin upper lip, epicanthal folds, low nasal bridge, short midface, minor ear abnormalities
Prevalence of FAS in Australia
0.06% in Australia, increase to 1.5% in remote FNQ
as high as 12% in some communities in Australia
estimated 38% Australian women drink while pregnant* (1st trimester), reduces to less than 7% after 1st trimester therefore craniofacial malformations are more common than neurological deficits
*why? they may not necessarily know they are pregnant, FAS affects in early weeks of pregnancy
Dental/orthodontic implications of FAS
- midface deficiency
- retrognathic md
- cleft lip and/or palate
- enamel hypoplasia (possibly)
few studies on dental effects, FAS is a spectrum, dont find all effects in all children
Which stage of embryonic development can Treacher Collins Syndrome occur
Migration of neural crest cells (19-28days)
Characteristics of Treacher Collins Syndrome
aka mandibulofacial dysostosis
- microtia (77%) or anotia
- conductive deafness (50%)
- zygoma deficiency (80%)
- mandibular hypoplasia (78%)
- cleft palate (30%) plus other associated facial clefting
Cause of TCS
3 gene mutations (1 present in 90% cases)
largely autosomal dominant (if parent carries 1 gene, likelihood is high)
mutation affects neural crest cells resulting in an overall lack of mesenchymal cells → causes lack of tissue in lateral parts of face
What is hemifacial (craniofacial) microsomia and cause?
mainly unilateral, 10-15% bilateral
defect of 1st and 2nd brachial arch
probably congenital but not inherited
might be associated with bleed of stapedial artery
(hypothesis: in early embryogenesis, mx and md artery feed the 1st brachial arch, facial feeds 2nd, normally these arteries are supplied by internal carotid, then stapedial artery breaks down and switches to external carotid - if there is bleeding when stapedial artery deteriorates can have defect on that side)
Given blood supply to 1st and 2nd brachial artery are disrupted in hemifacial microsomia, which structures would be affected? Name characteristics. What is the OMENS classification.
1st arch - mx and md, mm. mastication
2nd arch - mm. facial expression
- MAINLY mandibular and ear defects (usually absence of part of md)
- facial nerve weakness
- can also get maxillary hypoplasia
- signficant facial assymetry
OMENS says structures affected, way of classifying severity: orbits, mandible, ear, facial nerve, soft tissue/muscle deficiency
How may the mandibular defect in hemifacial microsomia range?
in mild form, all md structures present but one side slightly smaller
in severe form, whole ramus and condyle may be absent
What is craniosynostosis? Is it a syndome?
early closure of skull sutures
can be subdivided into syndromic and non-syndromic (80%)
Describe non-syndromic craniosynostosis
80% not associated with syndrome
very rare
head shape altered
Describe syndromic craniosynostosis. Name 4 clinical features
over 150 syndromes involving craniosynostosis
Crouzon’s syndrome (most common)
Apert’s syndrome (2nd most common)
clinical features differ but include:
- cranial vault deformities
- midface deficiency
- cleft palate
- hand and foot syndactyly (webbing)
Risk of increased intracranial pressure in non-syndromic vs syndromic craniosynostosis
non-syndromic: rare but can happen
syndromic: (happens because soft tissues continue to grow outward but supporting hard tissues cant catch up) cranial vault expansion may be required in early childhood, now usually do distraction osteogenesis
- can cause problems with neural development
- eyelids cant close - eye exposure can cause corneal abrasions, scarring and blindness
- compromised airways (maxilla cant come forward)
- feeding problems
Distraction osteogenesis is one of the most signficant changes in management of craniofacial syndrome. Why?
can achieve 1mm/day bone growth (14mm in 2 weeks which would be rly difficult w surgery)
no need for bone grafting
(surgeon does osteotomy, distractor device put in and turned daily)
Distraction osteogenesis is one of the most signficant changes in management of craniofacial syndrome. Why?
can achieve alot of bone growth, 1mm/day (14mm in 2 weeks which would be rly difficult w surgery)
no need for bone grafting
(surgeon does osteotomy, distractor device put in and turned daily)
Difference between syndrome and sequence
Syndrome - pattern of anomalies that occur tgt in a predictable fashion due to a single aetiology
Sequence - group of anomalies that generally stem from single major anomaly that alters development of surrounding structures e.g. Pierre robin sequence - small mandible cause other issues such as airway obstruction
What is Pierre Robin Sequence caused by? How does it present/why
micrognathia (small md) caused by posture in utero → elevation of tongue obstructs upper airway and causes cleft lip and palate and breathing problems
(*fetus chin against chest, stopping md from coming forward, tongue trapped and moves upward - fusion of palatal shelves requires for the tongue to be descended → cleft)
Facial development summary (for lip formation)
face formed between 4-10th week of pregnancy by fusion of 5 facial swellings:
- unpaired frontonasal process (frontal prominence)
- pair of maxillary swellings
- pair of md swellings
the mx and md swellings constitute dorsal and ventral regions respectively of 1st pharyngeal(brachial) arch, and give rise to upper and lower jaws
frontal prominence is part of forebrain (pink in pic), comes down to form median and lateral nasal process which fuse tgt
at around week 6, maxillary process fuse against median nasal process forming the lip and primary palate
*rmb: mx and md BOTH form from 1st brachial arch
Philtrum and part of alveolus holding upper centrals are formed by what?
forebrain, NOT 1st brachial arch
Cleft lip vs palate in terms of formation
separate processes that can happen tgt or alone, happen at different times and fusion of different structure
cleft lip = when median nasal process and maxillary process dont fuse - lips and primary palate
cleft palate = when secondary palatal shelves dont fuse
Embryologically, does cleft lip only affect soft tissue i.e. lip?
while it can be just the lip, embryologically, it is also the premaxilla area aka primary palate
Facial development summary (for secondary palate formation)
d. during 6th week of embryognesis, palatal shelves develop as bilateral outgrowths from the maxillary processes (2 mesenchymal projections) which grow vertically down the side of the tongue
e. palatal shelves elevate to a horizontal position above the tongue (tongue must descend out of the way), contact eachother and fuse (first fuses at FRONT then progressively back - can have partial clefting, most minor form is bifid uvula)
f. 2 palatal shelves fuse with eachother and nasal septum and posterior part of primary palate, ultimately divides oronasal space into oral and nasal cavities
What must tongue do when palatal shelves fuse?
must descend out of the way
in Pierre Robin, it can’t due to lack of space
also sometimes tongue does move out of way but for some reason palatal shelves dont fuse
When/why do other facial clefts occur (very rare - just to know)
clefts arise due to failure of facial prominence/processes to fuse between week 4 and 10
e. g.) failure of fusion between mx process and median and lateral nasal processes → cleft going through lip, up side of nose and towards eye
e. g. 2) failure of fusion between medial nasal processes→ midline cleft
e. g. 3) failure of fusion between mx and md processes → cleft out of side of lip
Cleft lip classification
Cleft lip (CL) involves the lip and alveolus
Can be unilateral or bilateral
Cleft palate classification
Cleft palate (CP)
Alveolus and lip not involved!
Not unilateral or bilateral - just cleft of palate
How would this be classified
unilateral cleft lip and palate (UCLP)
How would this be classified
bilateral cleft lip and palate (BCLP)
What are the Kernahan’s and LAHSHAL classifications
Kernahan’s: Y shape representing different structures which are numbered, shows which are affected
LAHSHAL: (lip, alveolus, hard palate, soft palate) starting upper right, lower case for incomplete cleft → made for ease of entering onto computer
What is the aetiology of CLP
precise aetiology unknown, still ongoing research
~30 associated genes identified but inheritance doesnt follow normal Mendelian pattern (MSX-1)
mixed aetiology: can either be highly predisposed genetically and need very small environmental insult in order for cleft to express OR very undisposed genetically but higher environmental insult
environmental factors:
- retinoids (acne/skin treatments)
- smoking
- alcohol
- ?illicit drugs
- drugs: Phenytoin, Trimethoprim (rare antibiotic)
- Folic acid/Folate (preventative for cleft lip but not palate)
(aus govt mandates adding folate to all flour that makes bread to stop neural tube defects in embryogenesis, also protective effect against CL)
CLP diagnosis (before birth)
usually during week 20 ultrasound
- 2D ultrasound detection rate is poor (20%)
- 3D ultrasound much better (90-100%)
- Colour Doppler Ultrasound can also visualise abnormal flow of amniotic fluid from mouth to nasal cavity
CLP treatment (by age group)
- pre-natal: counselling/support groups + arrange referral to cleft centre
- 0-1 y: acrylic plates for nasoalveolar molding and to stop tongue from resting in cleft + cleft lip and palate surgical repair (soft tissues)
- 2-5y: speech therapist/ENT - assess hearing and speech + F/S & preventative paed dent
- 7-9 y: first stage of orthodontic tx to prepare for alveolar bone grafting (provide bone for canine when root ⅔s formed)
- 10-15y: conventional ortho records
- 18+: orthodontics +/- orthognathic surgery (if needed), restorative (50% missing lateral), rhinoplasty, revision of cleft repair
What is the GOSLON Yardstick
UK had many ~57 cleft units (good accessibility so ppl can travel from homes) but with poor standards/results so they teamed up with Norway (only 2 units but very specialised teams) to create standards and compare → UK then reduced and only 5 craniofacial now (surgical teams must complete atleast 50 cases/year - therefore proficient)
- Australia also has highly centralised and high standard cleft care
Specialists in cleft management team
