Cleft Lip and Palate
History
Lagocheilos – “Harelip” – coined by Galen
Bec de lievre – “Lip of the hare” – Ambroise Pare
EVOLUTION OF SURGICAL TECHNIQUES
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Ambroise Pare writings about bec de lievre (lip of the hare)
390 AD1st lip repair by an unidentified Chinese physician
1295-1350 Yperman creditied with the original description cut edges and sutured the margins
early techniques involved straight line closure such as that by Rose and Thompson
1843 Malgaine introduced the use of local flaps
Mirault utilized the principle of filling the medial deficit with a lateral flap
1884 Hagedorn applied the z-plasty and a rectangular flap
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Earliest records of cleft closure date back to 390 AD in China.
Yperman (1295-1350) and later, Ambrose Pare (1564) - Pared the cleft edges, approximated the lip,
fixed it with a straight needle passed through both lip elements and wrapped a figure of 8 thread
around the needle.
Early techniques used a straight line closure, eg.: Rose (1891) and Thompson (1912)- Angled
incisions to lengthen the cleft edges.
Malgaine (1843) - Introduced the idea of a local flap to close the cleft lip.
Mirault (1844) - Modified Malgaine’s technique and brought a lateral flap across to fill the defect.
This is the principle on which all subsequent methods rely.
Hagedorn (1884) - Z-plasty technique.
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First half of the 20th century was devoted to straight-line repairs.
Blair-Brown (1930) and Brown-McDowell (1945) modified Mirault’s original technique by
reducing the size of the triangular flap, which they brought into the lip. This produced a nearly
straight-line scar, no Cupid’s bow and an asymmetrical vermilion tubercle.
Le Mesurier (1949) - Modified Hagedorn’s technique (1892) - Transposed a lateral quadrilateral
flap across the cleft into a medial releasing incision. Amending the shape of the flap, he could create
an artificial Cupid’s bow.
Tennison (1952) - Z-plasty closure using triangular flaps which preserved the natural Cupid’s bow.
Both Tennison and LeMesurier introduced tissue into the lower part of the lip, which produced a
more natural pouting of the tubercle. These repairs were popular in the 50’s and early 60’s.
Randall (1959) - Defined the mathematics of the Tennison method and reduced the size of the
inferior triangular flap.
1955 Millard developed the concept of lateral flap advancement into the upper potion of the lip
combined with downward rotation of the medial segment places tension under the alar base,
reduces flare and promotes better moulding. technique preserves Cupid's bow and the philtral dimpl
Davies (1966) - Z-plasty (triangular flaps). Later modified by Fernandes and Hudson - smaller Z
placed just below the nostril sill.
Wynn (1960) - Lateral flap.
Skoog, Trauner - 2 flaps in both the upper and lower portion of the lips.
DAVIES (1971) - THE UNILATERAL CLEFT LIP SURGICAL FAMILY TREE:
Straight line
Repair
Ambrose Pare
Lateral Flap
Medial Flap
Z-Plasty
Owen
Von Langenbeck
Hagedorn
Rose
Mirault
Thompson
Blair and
Brown
Veau
Barrett, Brown
and McDowell
Kilner
Axhausen
(?Nakajima)
Le Mesurier
Tennison
Skoog
Davies
Millard
rotation
advancement
(Fernandes)
EMBRYOLOGY
See also CF embryology
 The mesoderm in facial development is specialized tissue that begins to differentiate at day 21
 Neural crest cells differentiate from the ectoderm and separate the neuroectoderm of the neural tube
from the covering cutaneous ectoderm termed ectomedenchyme
 migrates alone cleavage planes between mesoderm, ectoderm and endoderm
 Organized migratory behavior dictated largely by local factors in their environment
 Migration of this ectomesenchyme over and around the head is essential to the development of facial
processes
 Its failure in the migratory pattern and path of the ectomesenchyme tissue that are responsible for
clefting in the face, lip and palate
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In the normal sequence the frontonasal processes evolve over the developing brain.
Maxillary and mandibular processes evolve around the stomatodeum and the branchial arches
Primary Palatogenesis
 frontonasal process is split into central and lateral processes by the olfactory placodes
 Central process is buried by the progressive ingrowth of the maxillary process after it has joined
with both the medial and lateral nasal prominences
 The upper lip is completed on either side of the globular prominence is formed by fusing
 with the freely projecting medial nasal prominences of the frontonasal prominence
 Primary palate is formed by fusion of the maxillary processes with the frontonasal processes
 Closure of the primary palate occurs between the 4th and 8th week
 Hard palate fuses from anterior to posterior
 Forms a triangular area of the anterior hard palate extending from anterior to the incisive foramen to a
point just lateral to the lateral incisor teeth. It includes that portion of the alveolar ridge containing the
four incisor teeth
 Primary palatal clefting occurs most commonly between the primary and secondary palates at the
incisive fissure that separates the lateral incisors and canine teeth
 Individuals with clefts of the primary palate may present with dental displacement or dental agenesis
from premaxillary hypoplasia
 Labial defects typically involve discontinuity of the circumoral musculature and reduced lip muscle
volume in cleft embryos and fetuses
Secondary Palatogenesis
 The secondary palate is defined as the portions of the facial primordia posterior to the primary palate
and includes the two lateral palatal processes that project medially from the maxillary processes.
 The primordia of the secondary palate forms the hard (bony) palate, the soft palate (the velum), the
alveolar and basal bone of the maxillae, and the associated dentition posterior to the incisive fissure
 During week 8 postconception, the palatal shelves rotate from a vertical position surrounding the
tongue and elevate into horizontal approximation.
 Right palatal shelf assumes a horizontal position before the left (may explain the preponderance of
left sided clefts in mammals)
 secondary palate closes 1 week later in females, which may explain why isolated clefts of the
secondary palate are more common in females
 The tongue must migrate away from the shelves in an antero-inferior direction for palatal fusion to
occur.
 Rapid palatal shelf elevation is thought to result from a number of mechanisms:
1. developmental changes in the connective tissue matrix and associated glycosaminoglycans of the
shelves leading to hydration, swelling, and rapid elevation
2. a change in shelf vascularity leading to increased tissue fluid pressure and turgor
3. rapid differential mitotic growth of the shelf mesenchyme;
4. movements of the tongue, facial, and suprahyoid musculature leading to cranial flexion,
swallowing and mandibular depression, tongue withdrawal from the cleft, and hence shelf closure
 FGF8 and SHH expression are found along the medial edge of the maxillary prominence and
presumably are involved in growth and elevation of the palatal shelves
 Once the palatal shelves are elevated and approximated, adhesive contact, seam fusion along the
medial edges, and apoptosis of the epithelium are essential for normal secondary palatogenesis.
 An increased expression of the cell adhesion molecule syndecan is seen during shelf elevation.
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Cleft of the secondary palate can thus be due to
1. failures of elevation
o leads to wide clefts
2. failures of contact and adhesion
3. failures of fusion
Major factors shown to limit shelf contact include
1. delayed shelf movement to the horizontal position
2. reduction in palatal shelf size
3. deficient extracellular matrix accumulation
4. delayed achievement of mandibular prominence
5. head extension (thus an increase in facial vertical dimension)
6. abnormal craniofacial morphology
7. abnormal first arch development,
8. increased tongue obstruction of shelf movement secondary to mandibular retrognathia, growth
retardation or chondrodysplasia in Meckel’s cartilage
9. amniotic sac rupture leading to severely constricted fetal head and body posture
A cleft of the lip/primary palate increases in probability of a cleft of secondary palate
developing. The cleft of the lip occurs earlier(week 6) and inhibits tongue migration, which may then
prevent horizontal alignment and fusion of the palatal shelves.
Two theories in embryogensis of facial clefting
1. classical theory
 Fusion of the ectodermal and mesodermal elements not unlike the healing of wound edges
 Secondary cleft due to failure to fuse (causes above)
2. mesodermal penetration theory
 Closure between the processes depends on mesodermal reinforcement at key points along these
migratory routes
 Clefts result from lack of reinforcement between epithelial layers with subsequent breakdown and
epithelial separation
 Primary cleft due to inadequate mesenchymal migration between the maxillary and medial nasal
processes results in bilateral or unilateral clefting of primary palate (ie, lip or maxillary alveolus)
CLASSIFICATION
Facial clefts may be typical, atypical or bizarre (amniotic band)
EPIDEMIOLOGY
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Frequencies: 20% isolated CL, 30% isolated CP, 50% CLP
Racial variations
 Asians 2.1/1000 live births
 Caucasians 1/1000
 0.41/1000 New World Blacks
 1/750 Perth
 No racial heterogeneity in isolated CP
 Embryonic face shape, as a predisposition for primary palatal clefting, helps explain the observed ethnic
(Asian derived > European derived > African derived) and gender differences (males 2:1 over females) in
the frequencies of primary palatal clefting
Inheritance
 population risk = 0.1%
 33% have a positive family history of clefting
 1 parent with cleft; first child has a 4% chance, next child 15%
 2 parents with a child with a cleft then next child has a 2-4% chance of cleft
Sex
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CLP more common in males 2:1
CP more common in females 2:1
Side of cleft
 CL/P are more common on the left side
 6:3:1 unilateral left-sided, unilateral right-sided, bilateral
 bilateral CL is associated with CP in 86% of cases while only 68% of unilateral cases are associated
with cleft palate
Parental age
 incidence increases with age
 paternal age more significant
Seasonal incidence
 oral clefts more common in Jan and Feb ?
Birth order
 The birth order has no bearing on cleft
Social class
 Some assoc with lower socio-economic class - related to poorer nutrition
Associated defects
CL/P
1. CNS
2. Club foot
3. Cardiac abnormalities
 The overall incidences of associated anomalies in all cleft cases are 29% with isolated cleft palate having
the highest incidence
ETIOLOGY
 CL/P is distinct from CP
 Both tend to cluster in families
i. 1/3rd of CL/P and CP have a positive family history
ii. Rest probably environmental
iii. familial twice as often in CL/P as in CP alone
 Clefts may occur as part of
iv. Malformation – Defect in an organ, part of organ or region, stemming from a defect in
morphogenesis
v. Disruption – Results from the extrinsic breakdown of an originally normal developmental
process.
vi. Deformation – Abnormal form, shape or position of a part of the body caused by mechanical forces.
 Cleft Deformities are either syndromic or nonsyndromic (majority)
i. syndromic if the patient has more than one malformation involving more than one developmental
field
ii. Cleft is non syndromic when there is either a singular defect or multiple anomalies that are the result
of a single initiating event
 20-50% of nonsyndromic orofacial clefts have a genetic component, the rest due to environmental factors
or gene–environment interactions
Syndromes associated with clefts
 Syndromes are more common in isolated CP than in CL/P
 Genetic defects may be chromosomal or single gene abnormalities, affecting structural, enzymatic or
regulatory (signaling/transcription) proteins
Stickler’s syndrome
 Most common in the CP alone group is stickler syndrome(17.5% of syndromic clefts)
1. Autosomal dominiant condition with mutation in the gene for type 1 OR 2 collagen
2. CP
3. Myopia
4. Retinal detachment
5. Glaucoma
6. Results from a mutation in the gene for type 2 collagen
Van der Woude's syndrome
1. AD penetrance 70-100%, variable expression; 30-50% sporadic; deletion at chromosome 1q
2. 1 in 75,000 to 1 in 100,000 births, 1% to 2% of patients with cleft lip or palate
3. Bilateral paramedian lower lip pits
 characteristically present as symmetric pits close to the vermillion border of the lower lip,
approximately 0.5 cm off the midline, and are usually connected with heterotopic salivary
glands
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presence of a sinus is directly related to the severity of the cleft lip, palate, or both
Treatment:
i. simple excision of the sinuses and adjacent glands that empty into the sinuses is the
most commonly accepted procedure
ii. split-lip advancement technique - two opposite labial artery-based flaps, including the
whole thickness of the vermillion and the mucosal surface of the lip, are used to repair
the median defect that results from excision of the sinuses.
 other syndromes with pits/sinuses
i. Popliteal pterygium syndrome is a rare, autosomal dominant anomaly with a variety of
manifestations, including lower lip sinuses, popliteal webbing, cleft lip, cleft palate,
syndactyly, and genital and nail anomalie
ii. Type 1 orofaciodigital syndrome includes lower lip sinuses, clefts of the jaw and
tongue in the areas of the lateral incisors and canines, malformations of the face and
skull, and mental retardation
4. hypodontia (10-20%) - congenital absence of the second molars
5. CL (16%)or CL/P(66%) or CP(17%)
6. The risk for affected parents children is 22 %
Unusual among syndromic forms of clefting in that clefts of the secondary and primary palates are
seen in the same families.
Twins, left- operated cleft lip with unilateral lower lip sinus. Right - bilateral symmetrical lower lip sinuses
with nonoperated soft palatal cleft
Pierre Robin sequence
1. micrognathia
2. glossoptosis
3. Cardiac and eye defects
4. U shape Cleft palate
Treacher Collins
1. AD
2. Absent zygoma
3. External and middle ear defects
4. Cleft palate-40 %(wide posterior)
Waardenburg syndrome
Features
i. Lateral displacement of the medial canthi combined with dystopia of the lacrimal puncta and
blepharophimosis
ii. Prominent broad nasal root
iii. Hypertrichosis of the medial part of the eyebrows
iv. White forelock
v. Heterochromia iridis
vi. Deafmutism
Velocardiofacial syndrome
Chromosomal
 Rearrangements that can include clefts of the primary palate (the secondary palate) include deletions of
4p (Wolf-Hirschhorn syndrome), 4q or 5p (Cri-du-chat syndrome); duplications of 3p, 10p, and 11p; and
trisomy 13 or 18 (and trisomy 9 mosaic)
 Clefts of the secondary palate alone are seen with deletions of 4q and 7p; duplications of 3p, 7p, 7q, 8q,
9q, 10p, 11p, 14q, 17q, 19q; and trisomy 9 or 13
Klippel Feil syndrome
 Classic triad of low posterior hair line, short neck and limited neck ROM
Environmental agents
 All studies in animals and teratogens are species specific
 These agents interfere with the normal fusion of the facial prominences
 Agents
1. Anticonvulsants (10 times increase risk of CL)
2. 13-cis-retinoic acid
3. Corticosteroid (4x increased risk)
4. Amniotic sac puncture (Amniotic band)
5. Alcohol - effects on neural crest cells, their migration and differentiation .Women who consumed
five or more drinks per week showed increased risk of having a child with isolated cleft lip/palate
(odds ratio = 3.4)
6. Smoking – dose response relationship - 2 times increase in risk of CL with >21cigarettes/day
7. Vitamin deficiency (vit B12 and folate) - B12 and folate noted with 65% decrease in the
incidence of clefts but need to start the drug 2 months before conception
8. Dioxin (Agent Orange)