CODI 546  Craniofacial Anomalies
Clefts of the Lip & Palate:  Development & Classification

What is a Cleft?
  1.  Abnormal opening or fissure in a structure that is normally closed
  2.  In congenital clefts, all structures are present but have not fused together normally
  3.  Some structures may be hypoplastic or underdeveloped
  4.  Embryological development has to occur in a certain sequence & within a specific time frame -if anything disrupts or delays the process the resulting structure will be malformed giving rise to clefts, abnormally shaped structures, etc.
Early Cell Development
  1. Development of craniofacial complex begins during second month of gestation (6-7 weeks) & is essentially complete by 12 weeks or end of first trimester
  2. Neural crest cells first differentiate into 3 layers
    1. Endoderm
    2. Mesoderm
    3. Ectoderm
  3. 3rd to 4th week gestation
    1. Digestive tract develops - gut, foregut
    2. Flexion occurs creating stomodeum - primitive mouth
    3. Stomodeum connects to foregut during 4th week
Facial Processes
  1.  Develops from 5 swellings or processes
    1.  Frontonasal
    2.  2 maxillary
    3.  2 mandibular
  2.  Mandibular processes merge & fuse
    1.  Mandible, lower lip & chin
  3.  Nasal placodes & olfactory pits develop giving rise to nasomedian & 2 lateral nasal processes
    1.  develop into nose, midportion of lip & premaxilla
  4.  Maxillary processes merge & fuse
    1.  Cheeks & lateral upper lip


Formation of Palate
  1. Primary palate (lip, alveolar ridge, premaxilla)
    1. Nasomedian process grows down and back to form medial portion of alveolar ridge & premaxilla bone
  2. Secondary palate (hard & soft palates)
    1. Internal surface of maxillary processes develop into 2 palatal shelves growing medially but vertically
    2. Mandible & tongue drop allowing shelves to grow horizontally
    3. Palatine processes meet and begin to fuse with primary palate along incisive suture lines & with each other along median palatine suture line beginning at incisive foramen & with inferior edge of vomer
    4. Muscle tissue also evolving and merging at midline

Process of Fusion
  1. Mesoderm - middle layer contains cells that can migrate & differentiate into other tissues
  2. As these cells multiply, processes grow closer & closer until they meet
  3. Theory of mesodermal penetration
    1. Two ectodermal layers meet and begin to breakdown
    2. Mesodermal tissue of each prominence migrate across & merge into one continuous layer
  4. Causes of cleft
    1. Failure of ectoderm to break down
    2. Insufficient mesoderm penetration
    3. 2 processes never meet
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Causes of Clefts
  1. Clefts begin at periphery and continue along suture lines to the point at which development was disrupted
  2. Occur due to disruptions or delays in cell migration or palatal shelf movement
  3. Four causes
    1. Chromosome disorders
    2. Genetic disorders
    3. Environmental teratogens
    4. Mechanical factors in utero
  4. Multifactorial inheritance
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Classification of Clefts:  Clefts of Primary Palate
  1. Structures that normally fuse around 7 weeks
  2. CL/P occur more often in males; more severe
  3. Complete cleft/incomplete
    1. Full vertical extinct of lip thru vermilion border, into nostril & through alveolar ridge
    2. Notch in vermilion border
  4. Unilateral/bilateral
    1. Follow philtral & incisive suture lines
    2. Unilateral is usually left
    3. Bilateral cleft results in separation of tissue of philtrum - called the prolabium

Classification of Clefts: Clefts of Secondary Palate
  1.  Structures that normally fuse at 9 weeks
  2.  CP occurs more frequently in females
  3.  Complete/incomplete
    1.  Extend from incisive foramen through velum & uvula
    2.  Bifid uvula or cleft of velum only
    3.  Palatal fissure - hole in palate is result of repair breakdown
  4.  Bilateral/unilateral
    1.  Unilateral - vomer attached to one side of palate; usually associated with unilateral cleft of primary p.
    2.  Bilateral - vomer is unattached; can be seen at midline

Classification of Clefts:  Submucous Clefts
  1. Structures on oral surface are intact, but clefts are present in underlying structures of palate i.e. the bone or muscles
  2. Classic stigmata - visible on intraoral exam
    1. Bifid uvula
    2. Zona pellucida
    3. Notch in posterior border of hard palate
  3. Occult submucous cleft - effects only visible when examining nasal surface of velum

Classification of Clefts:  Facial Clefts
  1.  Midline clefts do occur though more rare - hard to explain embryologically but often associated with other midline problems
    1.  Holoprosencephaly - forebrain does not divide into 2 hemispheres
    2.  Hypertelorisim - wide spacing between eyes
    3.  Absent corpus callosum
    4.  Encephalocele - gap in skull with herniation of brain tissue into nose or palate
  2.  Lateral clefts - begin with mouth & extend laterally, horizontally, both upward & downward