Developmental Disorders

Human embryo at 7 weeks

Figure from Ten Cates Oral Histology, Ed., Antonio Nanci, 6th edition
 Development of the Face
The face begins to develop between the 24th and 38th
days of gestation by fusion of various tissue processes

Figures obtained from Before We Were Born; Moore and Persaud, 6th edition, 2003.
Frontonasal process

Figures obtained from Before We Were Born; Moore and Persaud, 6th edition, 2003.
Figures obtained from Before We Were Born; Moore and Persaud, 6th edition, 2003.
Figures obtained from Before We Were Born; Moore and Persaud, 6th edition, 2003.
 Formation of the Lips
Middle portion of the upper lip: Formed by the fusion of the
medial nasal process of both sides along with the frontonasal
process

Lateral portion of the upper lip: Fusion of the maxillary

processes of each side and medial nasal process

Lower lip: Formed by the fusion of the two mandibular processes

Cleft Lip
 Formation of the palate (weeks 7 to 9)

Palate develops from the primary palate and the secondary palate

The primary palate develops at about 28 days of gestation

Primary palate develops from the frontonasal and medial nasal

processes and eventually forms the premaxillary portion of the
maxilla

The secondary palate develops between 7th and 8th week of

gestation and completes in the 3rd month

The critical period of palate development is from the end of

6th week till the beginning of 9th week
 Formation of the secondary palate

Figure from Ten Cates Oral Histology, Ed., Antonio Nanci, 6th edition
Figure from Ten Cates Oral Histology, Ed., Antonio Nanci, 6th edition
Any defect in the development of these processes
or their fusion may result in orofacial clefts

Cleft lip- 25%

Cleft palate 30%
Cleft lip and palate 45%

CL CP are related etiologically and

Isolated CP is a separate entity
 ETIOLOGY of CL CP

Isolated clefts (non-syndromic): Heterogeneous inheritance

Syndrome-associated: 250 developmental syndromes (3% to 8%

of total clefts)

Single gene mutations; AD, AR or X-linked

Chromosomal abnormalities
Idiopathic
 Incidence of Orofacial Clefts

Most common congenital abnormality in humans

Racial variation of CL CP: White 1 in 700 to 1000

Asian 1.5 in 700 to 1000
Black 0.4 per 1000
Native Americans 3.6 per 1000

Isolated CP is much less common

Isolated CL: Males > Females (1.5:1)

CL + CP: Males > Females (2:1)
Isolated CP: Females > Males

80% of isolated CL: Unilateral (70% occur on left side)

Complete CL vs Incomplete CL
Variation in CP

Hard and soft palate or soft palate alone

Most minimal involvement: Bifid Uvula

Bifid Uvula: Most common

(1 in 80 in Whites;
1 in 10 in Asians and Native
Americans;
1 in 250 in Blacks)

Submucous palatal cleft: Defect in

underlying musculature alone;
A notch in bone also noted
 Pierre Robin Sequence (Pierre Robin Anomalad)
1. Mandibular micrognathia: Prevents descending of the tongue causing CP
2. Cleft palate: Wider and U-shaped than regular CP
3. Glossoptosis: Causing airway obstruction
Stigma of Orofacial clefts
Clinical appearance: psychological problems
Feeding and speech difficulties
Malocclusion due to collapse of the maxillary arch

Treatment: Multidisciplinary approach

Genetic counseling: Risk for cleft development in a sibling or

offspring is 3% to 5%

Risk increases to 10% to 20% if there is are affected first degree

relatives
Lateral Facial Cleft: Caused by lack of fusion of the maxillary and
mandibular process

Isolated or associated with mandibulofacial dysostosis

Oblique Facial Cleft: Failure of fusion of lateral nasal process and
the maxillary process

Extends from upper lip to eye

Always associated with CP

Median mandibular cleft: Failure of fusion of the mandibular processes
 Commissural Lip Pits
Small mucosal invaginations occurring at the corners of the mouth on
the vermillion border

Represents failure of normal fusion of the maxillary and mandibular

processes

12% to 20% (so common); Autosomal dominant where reported

Associated with high incidence of preauricular pits

No treatment necessary
 Paramedian Lip Pits
Autosomal dominant

Arise from persistent lateral sulci on the embryonic mandibular arch

(these should normally disappear by 6 weeks of embryonic age)

Van der Woude Syndrome: Paramedian lip pits associated with CL CP

 Double Lip

Redundant fold of tissue on the mucosal side of the lip

Mostly congenital but also acquired as a result of trauma, oral

habits such as sucking on the lip or as part of Ascher syndrome

Upper lip > lower lip

Ascher syndrome: AD; Double lip; bleparochalasis and nontoxic

goiter
 Fordyce Granules or Disease

Sebaceous glands occurring on oral mucosa considered ectopic

Considered normal variation as reported in >80% of the population

Buccal mucosa and vermillion zone of upper lip

Occasionally they become hyperplastic or form keratin-filled cysts

 Leukoedema

Diffuse grayish-white appearance of mucosa

Blacks > Whites
Variation, not a disease
More prominent in smokers
Buccal mucosa extending to the lips
Thick epithelium; intracellular edema
No treatment
Amyloidosis
 Macroglossia

Enlargement of the tongue

Refer to Box 1-1 in the text book for common causes of

macroglossia

Congenital or Hereditary:
Vascular malformations: Hemangioma, lymphangioma
Hemihyperplasia
Metabolic diseases: Mucopolysaccharidoses
Syndromes: Downs, Beckwith-Wiedemann

Acquired:
Edentulous patients
Amyloidosis
Myxedema
Acromegaly
Tumors
 Ankyloglossia (Tongue-Tie)
Short thick lingual frenum resulting in limitation of
tongue movement

Speech defects
Thyroid gland development (4 to 7 weeks)

Figures obtained from Before We Were Born; Moore and Persaud, 6th edition, 2003
 Lingual Thyroid

Small remnants of thyroid tissue seen in 10% of populations

Actual lingual thyroid less common (Females > Males)

Hypothyroidism reported in 30% of cases

Rarely carcinomas develop (which is more common in males so

prophylactic removal recommended for men > 30 years)
 Fissured Tongue
Grooves and fissures
2% to 5% of population
Entire tongue or part
Usually asymptomatic
Prevalence increases with age
Strong association with geographic tongue and Melkersson-
Rosenthal syndrome
Tongue brushing

Melkersson-Rosenthal syndrome:
Fissured tongue
Orofacial granulomatosis
Facial paralysis
 Hairy Tongue

Marked hyperkeratinization of filiform papillae

Less than 1%
Smokers, antibiotics, poor oral hygiene, radiation, general
debilitation
Staining (bacteria, coffee, tobacco)
Asymptomatic
Brushing
DO NOT USE KERATOLYTIC AGENTS
If you do not know how
 Varicosities

Dilated and tortuous vein

Age-related
Loss of connective tissue tone
No association with hypertension or cardiopulmonary
disease
Sublingual area
Multiple or solitary
Phleboliths
 Exostoses
Localized bony protuberances arising from the cortical plate

Torus palatinus and Torus mandibularis

Buccal exostoses: bilateral row of bony hard nodules along the facial
aspect of maxillary and/or mandibular alveolar ridge

Palatal exostoses: lingual aspect of tuberosity

Solitary exostoses: Trauma; local irritation

Reactive subpontine exostoses (subpontic osseous hyperplasia): develop

From alveolar crestal bone beneath the pontic of a posterior bridge

Radiograph: Radiopacity

Histology: Mass of non-neoplastic bone with minimal marrow

Treatment for painful/ulcerated cases or if diagnosis is uncertain

Subpontic Osseous Hyperplasia
 Torus Palatinus

Midline of palatal vault

Multifactorial, genetic predisposition
Flat, spindle, nodular, lobular
Rarely show on PAs
More women than men
Surgical excision to accommodate prosthesis
 Torus Mandibularis

Lingual aspect of mandible

Multifactorial
Bilateral
Single or multiple nodules
PAs: Periapical opacities that can be confusing
Not as common as torus palatinus
Surgical excision to accommodate prosthesis
 Eagle Syndrome
Elongation of the styloid process or mineralization of the stylohyoid process

18% to 40% incidence of the general population

Mostly asymptomatic but some experience eagle syndrome caused by

compression of the adjacent nerves or blood vessels

Vague facial pain while swallowing, turning head or mouth opening

Dysphagia, dizziness and transient syncope (fainting)

PAN or lateral radiographs

CLASSIC EAGLE SYNDROME OCCURS AFTER TONSILLECTOMY following

development of scar tissue in the area of the mineralized stylohyoid
ligament and cervicopharyngeal pain during swallowing
Carotid artery syndrome or stylohyoid syndrome: Elongated
mineralized complex impinges on the internal and external carotid artery
and associated sympathetic nerves

Traumatic eagle syndrome: Symptoms following fracture of the

mineralized stylohyoid ligament

Treatment:
Mild cases: No surgery; corticosteroid injections

Severe cases: Surgery

 Stafne Defect (Static bone cyst/defect)

Radiolucency with sclerotic border

Near angle of mandible (below the canal)
Anterior and upper ramus rarely
Usually normal salivary glands
Submandibular, sublingual, parotid
Asymptomatic
Striking male predilection
Developmental but not present from birth
Sialogram
 Hemihyperplasia (Hemihypertrophy)

Asymmetric overgrowth of one or more body parts

Actually hyperplasia of tissues rather than hypertrophy

Complex hemihyperplasia (whole side of the body)

Simple hemihyperplasia (single limb)
Hemifacial hyperplasia (one side of the face)

2:1 female:male; Right side of the body

Enlargement more pronounced at puberty

Involves all tissues of affected side including bone

UNILATERAL MACROGLOSSIA; INCREASED CROWN OF TEETH

 Crouzon Syndrome (Craniofacial Dysostosis)
Craniosynostosis: Premature closure of sutures

Mutation in FGFR2; 1 in 65,000 births; AD

Wide variation in clinical presentation: Brachycephaly;

scaphocephaly; trigonocephaly; cloverleaf skull (kleeblattschdel)

Ocular proptosis: blindness and hearing deficit

Headaches; normal intelligence

Underdeveloped maxilla: Midface hypoplasia; crowding of

maxillary teeth; bifid uvula

Beaten metal skull in radiographs

Surgical treatment
 Aperts Syndrome (Acrocephalosyndactyly)
Craniosynostosis syndrome

Mutation in FGFR2; 1 in 65,000 to 160,000 births, AD

Acrobrachycephaly (tower skull); kleeblattschdel (severe cases)

Ocular proptosis; hypertelorism; vision loss; beaten metal

radiographs

Midface hypoplasia; V-shaped arch open-mouth feature;

hearing loss

SYNDACTYLY of the 2nd, 3rd and 4th digits; MENTAL RETARDATION

Pseudo cleft palate due to swellings (accumulation of glycos-

aminoglycans) of the lateral hard palate and crowding of
maxillary teeth; bifid uvula

Surgery
Treacher-Collins Syndrome (Mandibulofacial Dysostosis)

Defects of 1st and 2nd BA

AD; 1 in 25,000 to 50,000 births; 60% new mutations

Mutations in the TCOF1 gene

Characteristic face: Hypoplastic zygoma causing narrow face with

depressed cheeks and downward slanting palpebral fissures

Coloboma (notch) at the outer portion of lower eyelid

Ears anomalies: Deformed pinnae, extra ear tags, middle ear

ossicle defects cause hearing loss

Underdeveloped mandible; condyle and coronoid hypoplasia

Lateral facial clefting and cleft palate

No treatment required in most cases; Cosmetic surgery in

severe cases
 Osteogenesis Imperfecta

Heterogeneous group of disorders characterized by impairment

of collagen maturation

Mutations in type I collagen gene

Most common type of inherited bone disease

Collagen forms a major portion of bone, dentin, sclerae,

ligaments, and skin

Autosomal dominant, autosomal recessive hereditary; sporadic

Severity varies
 Osteogenesis Imperfecta

Weak bones, blue sclera, altered teeth, hearing loss,

long bone and spine deformity and joint hyperextension

Radiographic features include osteopenia, bowing,

deformity of long bones and multiple fractures

Oral manifestations are clinically similar to dentinogenesis

imperfecta premature pulpal obliteration

Shell teeth can also be noted

However the two are different processes caused by different

mutations

Opalescent teeth if associated with OI

Maxillary hypoplasia
 Osteogenesis Imperfecta

Four major types of OI

Type I: Most common and mildest form

Type II: Most severe; patients die before 4 weeks of age
Type III: Most severe form beyond the perinatal age
Type IV: Mild to moderate form

Treatment: No treatment of OI
Varied prognosis
 Cleidocranial Dysplasia

Caused by a defect in Cbfa1/Runx2 gene

Autosomal dominant and sporadic pattern

Bone defects involve the clavicle and skull

Clavicles are absent (unilateral or bilateral) 10% of cases

Short stature with large heads; ocular hypertelorism; broad

base of nose and depressed nasal bridge

Large heads and parietal bossing

Skull sutures show delayed closure and may remain open

Dental manifestations include narrow, high-arched palate

with increased prevalence of cleft palate
 Cleidocranial Dysplasia

Presence of numerous unerupted permanent and

supernumery teeth with many distorted crown and root shapes

Prolonged retention of deciduous teeth and delay or complete

failure of eruption of permanent teeth

Histology:
Unerupted permanent teeth lack secondary cementum

Treatment:
No treatment; full-mouth extractions with denture construction;
removal of primary and supernumery teeth followed by
exposure and orthodontic treatment of permanent teeth
 Osteopetrosis

Marked increase in bone density due to defect in osteoclast

function-L bone resorption along with continued bone formation

Infantile and Adult forms

Infantile: Severe disease-malignant osteopetrosis; AR

Anemia, infections, delayed tooth eruption, narrowing
of skull foramina
Fractures and osteomyelitis following tooth extraction

Adult: Less severe; AD; benign-osteopetrosis

Frequently diagnosed on routine X-rays; bone pain
Cranial nerve compression and fractures

Histology: K Osteoclasts and bone

Adult form: less severe

Infant form: Bone marrow transplantation