craniofacial syndromes by almuzian
TRANSCRIPT
University of Glasgow
Craniofacial Syndromes
Mohammed Almuzian
1/1/2013
Craniofacial Syndromes
Definition
A syndrome is the association of several clinically recognizable signs and symptoms, which
can occur together in an affected individual. A large number of syndromic conditions involve
the craniofacial region (Gorlin et al, 2001)
Classification according to mode of inheritance
1. Familial syndrome: Those that occur as part of a characterized Mendelian disorder,
resulting from a single gene defect:
• Autosomal dominant
• Autosomal recessive;
• X-linked dominant
• X-linked recessive
2. Sporadic syndrome: Those arising from structural abnormalities of the chromosomes;
due to teratogenic agents like:
• Drugs (alcohol, phenytoin, thalidomide);
• Infections (cytomegalovirus, rubella, syphilis);
• Physical agents (radiation, intrauterine mechanical restraint).
3. Idiopathic
Classification according to clinical features
I. Craniosynostoses
• Isolated craniosynostosis
• Apert's syndrome
• Crouzon's syndrome
II. Orofacial clefting syndromes
• Cleft lip and palate
• Pierre-Robin syndrome
III. Branchiat arch disorders
• Di George's syndrome
• Craniofacial microsomia
• Mandibulofacial dysplasia (Treacher Collins syndrome)
Mohammed Almuzian, University of Glasgow, 2013 Page 1
• Oro-facial-digital syndrome
IV. Syndromes affecting bone / cartilage
• Achondroplasia
• Cleido-cranial dysplasia
V. Others
• Binder's syndromes (maxillonasal dysplasia)
• Foetal alcohol syndrome (FAS)
In details:
Craniosynostoses
The craniosynostoses are a heterogenous group of disorders characterized by premature
fusion of the cranial sutures. This can occur in isolation or in association with other
anomalies, in a number of well-characterized syndromes
1. Isolated craniosynostosis
Around 1 : 2,000 children are born with premature fusion of a cranial suture
These cases usually occur sporadically but can also be familial.
Most commonly the sagittal; but the coronal, metopic (frontonasal suture) and
lambdoid sutures can also be affected.
The craniofacial features are dependent upon which suture is affected but usually
involve distortion of the skull due to excessive compensatory growth in unaffected regions.
Examples include:
A. trigonocephaly (fusion of the metopic suture),
B. Brachycephaly (fusion of the coronal suture and lambdoid suture bilaterally),
C. Dolichocephaly (fusion of the sagittal suture),
D. Plagiocephaly (fusion of coronal and lambdoidal sutures unilaterally),
E. Oxycephaly or turricephaly (fusion of coronal and lambdoid sutures).
Apert's syndrome
Aetiology:
• Autosomal dominant
• Defect in the FGF2 gene
• Prevalence of the disease (1 in 100,000)
Extraoral sign and symptoms
• Syndactyly of hand and feet (soft tissue and bone)
Mohammed Almuzian, University of Glasgow, 2013 Page 2
• Oxycephaly due to
Craniosynostosis of coronal and lambdoid
sutures
• Hyperteleorism
• Proptosis
• Midface hypoplasia
• Maxillary hypoplasia
• Class III malocclusion
Intraoral sign and symptoms
• High arched and narrow palate
• CLP
• AOB
• Crowding
• Small and missing teeth
• Delayed eruption
Crouzon's syndrome
Same as Apert syndrome except:
• Prevalence 1.6:100,000
• Craniosynostoses of coronal, sagittal and lambdoid
sutures
• Differential diagnosis - Aperts has syndactyly
Pierre-Robin syndrome
• Prevelance 10000-20000
• CP and CLP
• Retrognathic mandible but some claim 'catch-up' growth achieved
• Glossoptosis
• Respiratory distress. In many cases of PRS, the upper airway obstruction presents as a
medical emergency at birth, requiring neonatal nasopharyngeal intubation or tracheostomy.
However, once the airway is stabilized and a feeding regime put in place, these infants
usually thrive; with surgical repair of the cleft palate taking place during the first year of life.
Mohammed Almuzian, University of Glasgow, 2013 Page 3
It has been suggested that compensatory growth of the mandible may occur during the first 5
years in cases of PRS, but this is controversial.
Aetiology
• Several theories have attempted to explain why growth and development of the
mandible is so restricted in PRS:
1. Oligohydramnios or a increased amniotic fluid pressure compressing the chin against
the sternum and therefore restricting mandibular development (Poswillo, 1968);
2. A lack of mandibular movement during embryogenesis (secondary to muscle
weakness or hypotonia);
3. Genetic.
So, an excessively small mandible resulting in the tongue falling downwards and
backwards into the pharynx, being compressed between the palatal shelves and
preventing their closure. In addition to a large and U-shaped cleft palate, the tongue
position can also cause life-threatening respiratory difficulty at birth, obstructing the
epiglottis and preventing adequate inhalation of the lungs.
DiGeorge's Syndrome or 22q11.2 deletion syndrome
or velo-cardio-facial syndrome
Aetiology
• Embryonic insult during 4th-7th week IU. A syndrome
caused by the deletion of a small piece of chromosome
22. The deletion occurs near the middle of the
chromosome at a location designated 22q11.2—
signifying its location on the long arm of one of the pair of chromosomes 22, on region 1,
band 1, sub-band 2.
• Prevalence estimated at 1:4000
General sign and symptoms
• Cardiovascular anomalies (more severe cases), only 5% of patients have normal
hearts
• Congenital heart disease (40% of individuals), particularly conotruncal malformations
(tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and persistent truncus
arteriosus)
• Absence / hypoplasia of thymus ± parathyroid glands (mild cases)
Mohammed Almuzian, University of Glasgow, 2013 Page 4
• hypocalcemia (50%)(due to hypoparathyroidism)
• renal anomalies (37%)
• growth hormone deficiency
• autoimmune disorders
• immune disorders due to reduced T cell numbers
• learning difficulties (90%) but broad range
• hearing loss (both conductive and sensorineural) (Hearing loss with craniofacial syndromes)
• psychiatric disorders
Extraoral sign and symptoms
• Hyperteleorism
• Deep, low-set, small ears
• Blunted and cleft nose
• Micrognathia of the mandible
Intraoral sign and symptoms
• High arched palate
• ± CP/bifid uvula
Oculo-auriculo-vertebral Spectrum (Goldenhar Syndrome, 1" Arch Syndrome, 2nd
Arch Syndrome, Craniofaciai microsomia)
If it occurs unilaterally it will named hemifaial microsomia.
Craniofacial microsomia can be confused with Treacher Collins syndrome, but the latter
shows a well-defined pattern of inheritance and, unlike bilateral craniofacial microsomia, the
pathology is symmetrical. Treacher Collins syndrome has other distinguishing features
(absence of the medial lower eyelashes and absence of antegonial notching of the mandible),
findings that are absent in craniofacial microsomia.
Likewise, craniofacial microsomia should be distinguished from micrognathia of the
developmental or posttraumatic type. In the latter, the underdevelopment is restricted to the
mandible and there is no evidence of facial paralysis, ear anomalies, or soft tissue hypoplasia
of the cheeks.
General sign and symptoms
• Prevelance 1-5600
• Associated with heart and lung defects most commonly unilateral effects
Mohammed Almuzian, University of Glasgow, 2013 Page 5
Aetiology
• Despite the possibility of an occasional
autosomal dominant transmission, only a 2% to 3%
recurrence rate was found in a study of first-degree
relatives.
• Stark and Saunders invoked the concept of
mesodermal deficiency
• The most commonly accepted is a teratogen theory of a vascular insult, of stapedial
artery
Extraoral sign and symptoms
• Variable spectrum of presentation involving primarily Mandible+oral+ear+nerve
(OMEN)
• Deformities of pinna, microtia, ± ear tags
• Narrowing of palpebral fissure
• Vertical dislocation of orbit
• A reduction in size or flattening of the facial bones.
• Agenesis/hypoplasia of mandibular ramus on affected side
• A marked retrognathia, associated with mandibular asymmetry and canting of the
occlusal plane;
Intraoral sign and symptoms
• CL ± CP (7-15%)
• delayed tooth eruption
Hemifacial microsomia
Prevalence
1/5000 births but varies
Autosomal dominant
Affect male than female m:f = 3:2
Mohammed Almuzian, University of Glasgow, 2013 Page 6
A condition that affects aural, oral and mandibular development. It caused by
disturbance in the number, activity and migration of NCC (especially in the lower face area,
the NCC migrate for long distance)
Varies from mild to severe
Can be bilateral, and one side can be more severe than the other
Classification of HFM according to Przansky
1. Grade 1 condyle only
2. Grade 2 condyle and mild ramus involvement
3. Grade 3 condyle, ramus and coronoid severely involved
Aetiology
1. Autosomal dominance inheritances
2. Stapaedial artery bleeding
Features
The facial phenotype
1. General features: cardiac, renal and skeletal abnormalities
2. Facial features:
Unilateral microtia
Pre-auricular tags
Vertical dystopia
Facial asymmetry
Agenesis of the ramus
3. Oral & dental features:
CLP
Mohammed Almuzian, University of Glasgow, 2013 Page 7
Delayed teeth eruption,
Hypodontia
Hypoplastic teeth
Treatment Hemifacial microsomia
1. One way of treatment involves a costo-chondral graft, and a hybrid functional appliance in
different phases.
a. Very Early intervention at age of 5-6 years
Functional appliance
Then Surgery
Then functional appliance
b. Early intervention at age of 8-9 years
Surgery
Then Functional appliance
c. Late intervention
Orthodontic
Surgery
2. Second way of treatment distraction osteogenesis (DO).
It is a method of increasing bone length & originally described by Ilizarov (1988). The
technique involves:
1. Corticotomy – circumferential sectioning of compact bone and maintenance of
medullary complex.
2. Screw device holding bone pins rigidly and then the two pieces are separated in a
controlled and gradual process, which induces bony proliferation between them.
Mohammed Almuzian, University of Glasgow, 2013 Page 8
3. Screw turned after 5 days
1mm/day – adults
2mm/day – children
Insufficient speed = bony union
Undue haste = fibrous non-union
Advantages
More stable because of the gradual distraction of the soft tissue
Indication of DO
1. HFM
2. Treacher Collins syndrome
3. Ankylosis
4. Sever class III with maxillary hypoplasia
5. Sever class II with mandibular hypoplasia
6. Calvarial expansion in craniosynstosis
7. Missing bone due to trauma or pathology
Complications
1. Extra-oral scarring
2. Small and fiddly intra-orally
Mandibulofacial dysplasia (Treacher – Collins syndrome)
General sign and symptoms
• Prevelance 1-50000
• Autosomal dominant inheritance (variable expression)
Mohammed Almuzian, University of Glasgow, 2013 Page 9
• Mutations in the TCOF1, POLR1C, or POLR1D gene can cause Treacher Collins syndrome.
• Involves structures of 1st and 2nd arch
• Associated with cardiac defects, airway obstruction, oesophageal carcinoma
Extraoral sign and symptoms
• Deformities of pinna bilaterally, ± deafness
• Downwards sloping palpebral fissures
• Malar hypoplasia (body may be absent)
• Receding chin and hypoplastic condyle
• Large down-turned mouth
• Usually a severely class II skeletal pattern with increased vertical proportions, due to
mandibular deficiency and posterior mandibular growth rotation.
• Craniofacial microsomia can be confused with Treacher Collins syndrome, but the latter
shows a well-defined pattern of inheritance and, unlike bilateral craniofacial microsomia, the
pathology is symmetrical. Treacher Collins syndrome has other distinguishing features
(absence of the medial lower eyelashes and antegonial notching of the mandible), findings
that are absent in craniofacial microsomia.
Intraoral sign and symptoms
• CP (35%)
Oro-facial-digital syndromes
• 1 in 50,000
• Types I - VIII, all with similar features
• Orofaciodigital syndrome type 1 is caused by
mutations in the OFD1 gene.
Digital features
• Digital anomalies: brachydactyly, syndactyly,
polydactyly
Facial features
• Frontal bossing,
• Euryopia,
• Hypoplasia of alar cartilages
• Zygomatic hypoplasia
Oral features
Mohammed Almuzian, University of Glasgow, 2013 Page 10
• Pseudocleft of midline of upper lip (45%)
• Tongue hamartomas, clefts or lobulations
• CP - SP (80%)
• Fraenal hyperplasia
• Supernumeraries and hypodontia
Achondroplasia
• 1 in 25,000
• Autosomal dominant inheritance
• defect appears to be in the fgfr3 gene
• Defective development of endochondral ossification
• Frontal bossing
• Depressed nasal bridge
• Midface hypoplasia
• Ci iii malocclusion
• Achondroplasia is a misnomer because there is always
some cartilage present
Cleido-cranial dysplasia
General features
• 1 per million
• Autosomal dominant inheritance
• Defective development of intramembraneous
ossification - absent or vestigial clavicles
• Delayed closure of fontanelles and multiple wormian
bones
Extraoral features
Hypertelorism
Midface hypoplasia
Brachycephalic skull due to the presence of wide-
open sutures,
Mohammed Almuzian, University of Glasgow, 2013 Page 11
The presence of frontal bossing and midface hypoplasia, which leads to relative
mandibular prognathism and produces a characteristic facial appearance;
Endochondral bones can also be affected, with shortening of the long bones of the
axial skeleton and digits (brachydactyly). Together with the craniofacial features, this can
give an overall clinical impression of mild achondroplasia (dwarfism).
Intraoral features
± CP
High arched palate
Retained deciduous teeth;
Multiple supernumerary teeth;
Failure of eruption affecting the permanent dentition.
no cementum on teeth
Permanent teeth of individuals affected by CCD can be extremely resistant to
orthodontic traction
Orthodontic management
1. Lingual archs can be used to provide attachment to extrude multiple teeth after their
failure of eruption like Jerusalem approach (Becker, 1997) in the management of multiple
failures of eruption associated with Cleidocranial Dysplasia. With the Jerusalem Approach,
all primary teeth & supernumerary teeth are extracted at the age of 10– 12, closed exposure
with bonding of the permanent teeth is performed to start their alignment using the heavy
lingual and bucco-labial arch..
2. The Belfast– Hamburg (all surgical exposure and alignment done at one time at the age of
9 years, Unerupted permanent teeth are exposed at phase I, then at phase II (one year later)
the surgical exposure with orthodontic brackets are placed to start alignment (Behlfelt, 1987).
3. The Bronx approach developed recently by Berg in 2011 is similar to the Belfast–
Hamburg approach but involve additionally another Phase 3 where orthognathic surgery,
bone augmentation and dental implants are placed under at the same time.
4. The Toronto– Melbourne approach involves three stages. Stage I: at age of 6 years, the
primary incisors are removed. Stage II: at 9– 10 years where primary canines and molars are
removed while in stage III involve removing the supernumerary tooth and surgical exposure
of the permanent dentition at later age. (Smylski 1974;Hall, 1978)
Mohammed Almuzian, University of Glasgow, 2013 Page 12
Binder's syndrome or Nasomaxillary hypoplasia
• No ant nasal spine and thin alveolar plate around upper incisors
• Hypoplastic premaxilla
• Ci iii malocclusion
Foetal alcohol syndrome
• Narrow forehead
• Short palpebral fissures
• Small nose and midface
• Long upper lip
• Clp
Ectodermal dysplasia
The ectodermal dysplasias (ED) represent a heterogeneous group of conditions characterized
primarily by defective:
Clinical Manifestations of Ectodermal Dysplasia, Gill 2008
1) Skin
Dry
Hypopigmentation
Dermatitis
2) Sweat glands
Reduced or absent sweating
Reduced heat tolerance
3) Hair follicles
Sparse fair hair
Alopecia
Eyebrows or eyelashes absent/sparse
4) Nails
Dystrophic and malformed
5) Face
Cleft lip/palate
Frontal bossing
Depressed nasal bridge
Class III skeletal pattern
Mohammed Almuzian, University of Glasgow, 2013 Page 13
Reduced face height
6) Eyes
Cataract
Defective lacrimation
7) Nose
Rhinitis
Epistaxis
8) Dental
Hypodontia or Anodontia
Malformed teeth (cone- or peg-shaped)
Prone to caries owing to enamel defects and xerostomia
9) Salivary glands
Xerostomia
Syndromic CLP Eg. Van Der Woude Syndrome
• Autosomal Dominant
• 1 in 100,000,
• 2% CLP cases,
• Bilateral depressions of lower lip,
• Hypodontai
• Mild syndactyly
Osteogenesis imperfecta (OI and sometimes known as brittle bone disease, or "Lobstein
syndrome"
It is a congenital bone disorder characterized by brittle bones that are prone to fracture.
it, usually because of a deficiency of Type-I collagen
Most cases are caused by mutations in the COL1A1and COL1A2 genes.
The incidence of OI is estimated to be one per 20,000 live births
Mohammed Almuzian, University of Glasgow, 2013 Page 14
Features
Bones fracture easily
Slight spinal curvature
Loose joints
Poor muscle tone
Discoloration of the sclera (whites of the eyes), usually
giving them a blue-gray color. The blue-gray color of the
sclera is due to the underlying choroidal veins which show through. This is due to the sclera
being thinner than normal because of the defective Type I collagen not forming correctly.
Early loss of hearing in some children
Slight protrusion of the eyes
Absence/presence of dentinogenesis imperfecta (characterized by opalescent teeth; absent in
IA, present in IB).
Dentinogenesis imperfecta (DI)
It is a genetic disorder of tooth development. This condition is a type of dentin dysplasia that
causes teeth to be discolored (most often a blue-gray or yellow-brown color) and translucent
giving teeth an opalescent sheen.
Teeth are also weaker than normal, making them prone to rapid wear, breakage, and loss.
These problems can affect both primary (deciduous) teeth and permanent teeth.
This condition is inherited in an autosomal dominant pattern,
which means one copy of the altered gene in each cell is
sufficient to cause the disorder.
Dentinogenesis imperfecta affects an estimated 1 in 6,000 to
8,000 people.
Clinical features
The teeth may be gray to yellowish brown.
They exhibit translucent or opalescent hue.
Enamel is usually lost early due to loss of scalloping at the dentoenamel junction (DEJ).
However, the teeth are not more susceptible to dental caries than normal ones.
Mohammed Almuzian, University of Glasgow, 2013 Page 15
However, certain patients with dentinogenesis imperfecta will suffer from multiple periapical
abscesses apparently resulting from pulpal strangulation secondary to pulpal obliteration or
from pulp exposure due to extensive coronal wear.
Radiographic features Type I and II show total obliteration of the pulp chamber.
Amelogenesis imperfecta (AI)
Arkutu et al 2012 and Gadia 2012
0.5%
AI is caused by mutations or altered expression in five
genes: AMEL (amelogenin),ENAM (enamelin),
Systems used for classifying AI:
1. Mode of inheritance: autosomal dominant,
autosomal recessive, X-linked, isolated case
2. Phenotype: hypoplastic, hypocalcified,
hypomaturation, hypomaturation-hypoplastic with taurodontism.
Characterisitcs of hypoplastic AI Enamel of reduced thickness due to a defect in the formation of normal matrix
Pitting and grooves
Hard and translucent enamel
Radiographically, the enamel contrasts normally from dentine.
Characteristics of hypocalcified AI Defect in enamel calcification
Enamel of normal thickness
Weak in structure
Appears opaque or chalky
Teeth become stained and rapidly wear down
Radiographically, enamel is less radio-opaque than dentine.
Characterisitcs of hypomaturation AI Enamel of normal thickness but mottled in appearance
Mohammed Almuzian, University of Glasgow, 2013 Page 16
Slightly softer than normal and vulnerable to tooth wear, but not as severe as the
hypocalcified type
Radiographically, similar radiodensity as dentine.
Characteristics of hypomaturation-hypoplasia with taurodontism Mixed hypomaturation and hypoplasia appearance
Taurodontism: body and pulp chamber enlarged, and the floor of pulp chamber and furcation
is moved apically down the root.
DiagnosisFactors to consider during diagnosis include family history, pedigree plotting (a diagram of a family
health history tree), clinical observations and radiographic assessment. Further laboratory-based
genetic diagnosis can be done, but this is more useful as a research tool.
Complications It presents with a rare abnormal formation of the enamel or external layer of the crown
of teeth.
People afflicted with amelogenesis imperfecta have teeth with abnormal color: yellow, brown
or grey; this disorder can afflict any number of teeth of both dentitions.
The teeth have a higher risk for dental cavities and are hypersensitive to temperature changes
as well as rapid attrition, excessive calculus deposition, and gingival hyperplasia.
The developmental age of the patient should be used when assessing AI patients for tooth
eruption. Occasionally, space maintainers may be indicated to prevent tipping of adjacent
teeth into the space.
Impaction
Hypodontia
Root malformations have been considered a risk factor for orthodontic apical root resorption.
Taurodontism
Maxillay hypoplasia and AOB
X bite
Mohammed Almuzian, University of Glasgow, 2013 Page 17
Orthodontic Problems Bond strengths are lower than ideal, leading to multiple bond failures in treatment and the
need to step back to 'pick up' these teeth, thereby increasing treatment duration.
Debonding of the appliance can cause factures to the fragile enamel and must therefore be
performed with caution.
The lack of uniformity of enamel coverage means that the second and third order bends
(which are part of a pre–adjusted appliance prescription) are not uniformly expressed and
more detailing bends at the end stage of treatment are needed to counteract this when final
restorations using veneers and crowns are not indicated.
Light force to reduce resorption
Taurodontism: This feature of AI can increase the susceptibility to root resorption during
orthodontic treatment.
The use of removable appliances in the correction of malocclusion
Solutions Glass ionomer cement-based adhesives are thought to improve appliance retention as they are
less reliant on microtag formation, and also help in the reduction of further enamel
demineralisation.
Plastic brackets can be used instead of metal brackets because they can be removed with a
hand piece at debond without damaging the enamel surface.
Traditional banded appliances are old-fashioned, but may also be used to overcome some of
these problems. If the clinical crown height is minimal and banding is not possible, the use of
preformed stainless steel crowns with welded tubes or brackets is recommended.
Functional with HG to control AOB
Mohammed Almuzian, University of Glasgow, 2013 Page 18