craniofacial syndromes by almuzian

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)


• 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.


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)


• 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


• Hyperteleorism

• Deep, low-set, small ears

• Blunted and cleft nose

• Micrognathia of the mandible


• 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.



• Associated with heart and lung defects most commonly unilateral effects


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


• 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;


• 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


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


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.


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)



• Autosomal dominant inheritance (variable expression)


• 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


• 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.


• 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


• 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,


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)


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


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


http://en.wikipedia.org/wiki/COL1A2

http://en.wikipedia.org/wiki/COL1A1

http://en.wikipedia.org/wiki/Type-I_collagen

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.


http://en.wikipedia.org/wiki/Dental_caries

http://en.wikipedia.org/wiki/Dental-enamel_junction

http://en.wikipedia.org/wiki/Autosomal_dominant

http://en.wikipedia.org/wiki/Teeth

http://en.wikipedia.org/wiki/Tooth_development

http://en.wikipedia.org/wiki/Genetic_disorder

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


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


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


craniofacial syndromes by almuzian

Health & Medicine

deletion syndrome

familial syndrome

apert syndrome

digeorges syndrome

sporadic syndrome

aperts syndrome aetiology

digital syndrome iv

palate pierrerobin syndrome