Dr Adel Abdel-Azim

Professor of Oral Pathology, Ain-Shams University

Tempus Project-CD_JEP - 32112 - 2004

Dr Adel Abdel-Azim
Professor of Oral Pathology, Ain-Shams University

Tutankhamun Kings Mask

On March, 2005, Egyptian
archaeologist Zahi Hawass
revealed the results of a CT
scan performed on the
pharaoh's mummy.
The CT scan revealed that
the pharaoh had cleft palate
and an impacted wisdom
tooth.

Tutankhamun Cleft Palate Victim

Zahi Hawass, head of the
Egyptian Supreme Council of
Antiquities, looks on as the
3,300-year-old mummy of King
Tutankhamun is prepared for
CT scanning.
Photograph by Kenneth Garrett,
copyright National Geographic Society

Cleft Lip and Palate (CLP)

Definition
Prevalence
Embryological Basis
Embryological Classification
Pathogenesis of Clefts

Cleft Lip and Palate - Definitions

These are congenital clefts that may affect
lip, alveolus, palate or both

Cleft Lip & Palate - Prevalence

In Egypt the prevalence of cleft lip and palate is
1.66/1000 live births (Temtamy et al.)
Worldwide, the prevalence varies from 0.24/1000 live births
The highest prevalence rates are reported for
Native Americans and Asians.
The lowest prevalence rates was reported for
African-Americans.

Embryological Basis 5 Main Processes

From the forebrain a process known as the

frontonasal process grows downwards

This process then differentiate into 3 processes, one

in the middle known as the median nasal process
(Globular process) and two lateral processes known
as the lateral nasal processes

Meanwhile, two maxillary processes grow from the

first arch towards the central line of the face

Also in the same time period, the two mandibular

processes grow from the first arch towards the
midline of the face

Face Development

Face Development 6th Week

Face Development 6th Week

Forebrain
Frontal Process

Lateral Nasal Process

Maxillary Process
Mandibular Process

Frontonasal
P

Median Nasal Process

Face Development
Forebrain
Frontal Process

Lateral Nasal Process

Maxillary Process
Mandibular Process

Frontonasal
P

Median Nasal Process

Face Development

Frontal Process
Frontonasal Process
Maxillary Process

Mandibular Process

Fronto-Nasal Process

Median-Nasal Process

Lateral-Nasal Process

Maxillary Process

Mandibular Process

Embryological Processes of the Maxilla

LN Process
Globular Process

Maxillary Process

Palatal Process

GM = Globulomaxiallry process, M = Maxillary Process, PP = Palatine Process

The Problem of Upper Lip

Maxillary process overgrow and submerge the median nasal process

The Problem of Upper Lip

Maxillary process overgrow and submerge the median nasal process

The Problem of Upper Lip

Maxillary process overgrow and submerge the median nasal process

Cleft Lip & Palate

Fusion at meeting point between MxP, MNP &
LNP
MNP fuses with MxP first

Palate, Start of Fusion

Globular Process

Palatal Process

Palate, Start of Fusion

Globular Process

Palatal Process

Palate, Start of Fusion Note Lip

Globular Process

Palatal Process

Main Steps of Palatogenesis

Initially, they grow vertically
downwards by the sides of the
tongue. Later, they rotate or
elevate above the tongue, and
continue to grow horizontally,
until they meet in the midline
and adhere. Finally, the
epithelium disappears from
between the two apposed
shelves, thus allowing for
complete palatal fusion.

Main Steps of Palatogenesis

Main Steps of Palatogenesis

Initially, they grow vertically downwards by the sides of the tongue.
Later, they rotate or elevate above the tongue, and continue to grow
horizontally, until they meet in the midline and fuse. Finally, the epithelium
disappears from between the two apposed shelves, thus allowing for
complete palatal fusion.

Palatal Process

Tongue

Palatal Process

Palatal Fusion
Scheme summarizing the possible fates of cells forming the palatal
midline seam. (a) Pre-fusion palatal shelves are composed of the
mesenchyme (green), covered by two-layered epithelium comprising
the basal layer of cuboidal cells (light blue), and the superficial layer of
flat cells (periderm, dark blue). (b) Prior to contact of palatal shelves,
some (if not all) peridermal cells slough from the palatal surface into the
amniotic fluid, while others may die (red), and some may migrate into
the oral and nasal epithelium. It is highly controversial whether some of
the basal layer cells also slough or migrate. (c) Some of the peridermal
cells may become trapped between the two apposing shelves, where
they die and/or continue to migrate towards the so-called oral and nasal
epithelial triangles (the lower and upper areas of the midline seam,
MES). (d) Basal cells forming the palatal seam may disappear by the
cell death, migration, or transdifferentiation to the mesenchyme or
through any possible combination of any of these processes. It is not
clear, which of these processes prevails, but the transdifferentiation
concept seems to be the least important. (e) After disappearance of the
midline seam, mesenchymes of the apposed palatal shelves are
confluent, thus forming a united secondary palate.

Nefertiti The Beautiful Not Affected with CLP

The right Statue

is from Berlin
Museum,
Germany and
the left one is
from Flournce
Museum, Italy

Cleft Lip & Palate Etiological Classification

1. Syndromic (30% of cases)
1. Treacher collins syndrome
2. Pierre robin syndrome
3. Aperts syndrome
4. Van der Woude syndrome

2. Non-syndromic (70% of cases)

Cleft Lip & Palate - Classification

Embryological classification
1. Pre-alveolar clefts (Lip clefts)
2. Alveolar clefts (Primary palate clefts)
3. Post-alveolar clefts (Palatal clefts)

Cleft Lip & Palate - Classification

Pre-alveolar clefts (Lip clefts)
1. Unilateral
1. Incomplete
2. Complete

2. Bilateral
1. Incomplete
2. Complete
3. Mixed

3. Median cleft of the upper lip (Hare lip)

Cleft Lip & Palate - Classification

Alveolar clefts (Primary palate clefts)

Always associated with cleft lip
1. Unilateral
2. Bilateral

Cleft Lip & Palate - Classification

Post-alveolar clefts (Palatal clefts)
1. Cleft uvula (bifid uvula)
2. Cleft uvula + soft palate
3. Cleft uvula + soft palate + hard palate till the incisive
foramen
4. Cleft uvula, soft palate, hard palate till the incisive foramen
then the cleft includes the alveolus unilaterally.
5. As above but the cleft includes the alveolus bilaterally (the
condition often termed complete median cleft palate,
alveolus and lip).
6. Submucous cleft palate

Labial Clefts - Unilateral

Incomplete

Complete

Mention the direct cause of each cleft

Labial Clefts - Bilateral

Incomplete

Complete

Mixed

Labial Clefts - Median

Alveolar Clefts

Unilateral

Bilateral

NB: Always associated with labial clefts

Palatal Clefts

Cleft Uvula

Cleft Uvula

Cleft Uvula

+ Soft Palate

+ Soft Palate
+ Hard Palate

Complete Cleft Lip, Alveolus and Palate

Unilateral Complete Cleft Lip,

Alveolus and Palate

Bilateral Complete Cleft Lip,

Alveolus and Palate

Complete Cleft Lip, Alveolus and Palate

Cleft Lip Unilateral, Incomplete

Cleft Lip Bilateral, Incomplete

Cleft Lip Unilateral, Complete

Cleft Lip Unilateral, Complete

Bilateral Cleft Lip

Median Cleft, Upper Lip

Number Zero
Cleft:
Absent premaxilla
and septum.
Median cleft lip
and Abbe flap

Median Cleft Lip

Cleft Alveolus and Palate

Median Cleft of the Lower Lip Very Rare

In the literature so far, about 62 cases have been
described.

Median Cleft of the

Lower Lip

Bifid Uvula

Bifid Uvula with Hyperplastic Pharyngeal Tonsils

Cleft Palate

Oblique Facial Cleft

While the occurrence of some facial clefts can be
understandable in terms of failure of fusion of the various
primordial facial processes, others are not readily
explainable in such terms. A cleft that begins lateral to the
philtrum and extends to the mid portion of the lower eyelid is
difficult to explain. Events prior to the normal process of
fusion may lead to localized areas of tissue deficiency,
possibly resulting in these atypical clefts.
Source: http://www.emedicine.com/plastic/topic216.htm

Oblique Facial Cleft

Can be unilateral or
bilateral
Runs on the line occupied
by the nasolacrimal duct
Failure of fusion of
maxillary process in part
and lateral nasal and
median nasal processes
Often extends into the lip
and primary palate

Oblique Facial Cleft

Oblique Facial Cleft

Oblique Facial Cleft

Transverse Facial Cleft

Transverse Facial Cleft

Tessier number
seven cleft

Transverse Facial Cleft

Transverse Facial Cleft

Tessier number
seven cleft
associated with
Treacher Collins
Syndrome.

Transverse Facial Cleft

Tessier number
seven cleft
associated with
Treacher Collins
Syndrome.

Macrostomia

Pathogenesis
Syndromic clefts:

Are usually due to single gene defect and follow

Mendelian rules of inheritance

Non-Syndromic clefts:

Are due to multifactorial inheritance

Pathogenesis Single Gene Defects

Follow Mendelian pattern of inheritance
May be sex-linked or autosomal
May be dominant, recessive or of incomplete
dominance
May show varying degrees of expressivity
May show varying degrees of penetrance

Pathogenesis Single Gene Defects

The following genes are candidates for
developing oro-facial clefts:
IRF6 (interferon regulatory factor-6) associated
with Van der Woude syndrome the exact function
is unknown
PVRL1 (poliovirus receptor related-1) responsible
for autsomal recessive CLP-ectodermal dysplasia
syndrome
P63 (homologue for P53 tumor suppressor gene).
Its mutations were found to cause CLP in mice

Pathogenesis Multifactorial Inheritance

Multifactorial inheritance are diseases in which genetic

and environmental factors play an influential role.

Do not follow the Mendelian pattern of inheritance

Result from the action of more than one gene and can
be modified by the environmental factors

Many diseases follow this pattern e.g. hypertension,

diabetes mellitus, rheumatoid arthritis, peptic ulcer,
ischemic heart disease and cleft lip and palate

Pathogenesis Multifactorial Inheritance

The environmental factors responsible for cleft lip and
palate are not known precisely, however
the following factors were suggested:
Alcohol consumption
Smoking
Altitude hypoxia
Vitamin A excess or deficiency
Folic acid deficiency
Corticosteroids (proven in experimental animals)

Pathogenesis Multifactorial Inheritance

An interesting finding was that folic acid could
reduce the incidence of clefts in genetically prone
individuals

Tempus Project-CD_JEP - 32112 - 2004

Tempus Project-CD_JEP - 32112 - 2004

Thank You