CRANIOFACIAL ANOMALIES
CRANIOFACIAL
ANOMALIES
BY:DR IMTIAZ AHMED
BDS, FCPS
ORTHODONTICS

DiGeorge Syndrome
• Genetic disorder due to microdeletion of
Chromosome 22q11.2 (tbx-1 gene)
– The same genetic defect as VCF with different
phenotypic expression
• Characterized by:
– Hypocalcemia (due to hypoplastic parathyroids)
– Immunodeficiency due to hypoplastic thymus
– Congenital heart defects of the outflow tracts
(aorta and pulmonary artery).
•Reference: http://medicine.net

Treacher-Collins Syndrome
(Mandibulofacial dysostosis)
• Autosomal dominant, 40% will have family history, other 60%
new mutations
• Mutation inTCOF1 gene found on chromosome 5q (TREACLE
gene), it leads to loss of a specific exon.
• Malformation of 1st (& 2nd) branchial arches
• Otologic: Malformed ossicles, auricular deformity, aural atresia,
CHL present 30% of time, occasional SNHL
– 50% will have hearing impairment from EAC and/or middle ear
malformations
• Preauricular fistulas
• mandibular and malar hypoplasia
• antimongoloid palpebral fissures
• coloboma of the lower eyelids
• may have cleft lip and palate
• normal IQ

Treacher-Collins Syndrome
(Mandibulofacial dysostosis)
Figure 99.12 Treacher Collins syndrome. Zygomatic and mandibular hypoplasia, lower lid
colobomas, and downslanting palpebral fissures.
Reference: Bailey’s Otolaryngology-Head & Neck Surgery

Apert (acrocephalosyndactyly)
• Autosomal dominant, most cases due to
spontaneous mutation
• Due to a mutation of FGFR-2 (Fibroblast Growth
Factor Receptor) gene (10q26)
• Common findings:
– Craniosynostosis (pre-mature fusion of the cranial sutures)
– Severe symmetrical syndactyly
– Low-set ears
– Cognitive function normal to severe mental retardation
– Eyes: down-slanting palpebrael fissures, Hypertelorism,
Exophthalmos
– Midface hypoplasia
– Relative Mandibular prognathism
– Possible cleft palate
– Nose: Parrot-beaked nose, possible Choanal Atresia
– Syndactyly and cervical fusion

Figure 99.4 Apert syndrome has the additional feature of
syndactyly.
Reference: Bailey’s Otolaryngology-Head & Neck Surgery
Apert (acrocephalosyndactyly)

Crouzon Syndrome
(Craniofacial Dysostosis)
• Most frequently occurring member of cranisyntosis
• Autosomal dominant, 50% due to spontaneous
mutations, complete penetrance, variable expresivity
• Due to mutation of FGFR-2 (Fibroblast Growth Factor
Receptor) gene (10q26)
• Common findings:
– Craniosynostosis (pre-mature fusion of the cranial sutures)
– Hypertelorism
– Exophthalmos
– Midface hypoplasia
– Relative Mandibular prognathism
– Parrot-beaked nose
– No Syndactyly
– Cognitive function normal to severe mental retardation

Crouzon Syndrome
• Coronal and sagittal
sutures are most
commonly involved
• Cloverleaf skull is rare
and occurs in the most
severely affected
individuals.
• Hydrocephalus
(progressive in 30%)

Crouzon Syndrome
Midface (maxillary) hypoplasia
Exophthalmos secondary to shallow orbits
Ocular hypertelorism
Nose: Beaked appearance
Mouth: Mandibular prognathism
Narrow, high, or cleft palate and bifid uvula

Branchiootorenal Syndrome
(Melnick-Fraser Syndrome)
• Autosomal dominant, involves 8q between D8S87 and
D8S165 (EYA1 gene)
• Branchial cleft anomalies (63%): cysts or fistulae
• Otologic malformations:
– hearing loss (89%)
– preauricular pits (77%)
– auricle abnormalities (41%)
– ossicular & cochlear malformations
– 2% of children with severe/profound SNHL
• Renal Dysplasia (66%)
– agenesis, polycystic kidneys, duplicated ureters; renal
abnormalities identifiable on IVP or renal U/S

Branchiootorenal Syndrome
(Melnick-Fraser Syndrome)
Figure 99.6 Branchio-oto-renal syndrome. This 3-year-old boy has visible
cup-ear deformities. He also has branchial cleft fistulae and only one kidney.
Reference: Bailey’s Otolaryngology-Head & Neck Surgery

Down Syndrome
• Craniofacial Features:
– Brachycephaly
– Flat occiput
– Abnormal small ears
– Upslanting palpebral fissures
– Epicanthic folds
– Short small nose
– Midface hypoplasia
– Large fissured lips
– Large fissured tongue
– Dental abnormalities
– Short neck
– Atlantoaxial subluxation & instability

Goldenhar Syndrome
(Oculoauriculovertebral spectrum)
• Characterized by unilateral facial asymmetry,
unilateral external & middle ear changes, vertebral
malformations
• Ocular findings: upper lid colobomata
• Otologic findings: mildly deformed ears to anotia,
EAC atresia, ossicular abnormalities
• Underdevelopment of mandible, orbit, facial muscles,
also may have hemivertebrae of vertebral column
• Hemifacial macrosomia often placed in this category
• Most cases sporadic, some autosomal dominant
reported

Goldenhar Syndrome
(Oculoauriculovertebral spectrum)
Figure 99.8 Goldenhar syndrome. This 5-year-old boy has facial
asymmetry and right microtia.
Reference: Bailey’s Otolaryngology-Head & Neck Surgery

Pierre-Robin Sequence
• Triad of:
– Retrognathia - abnormal posterior positioning of
either of the jaws
– Glossoptosis - abnormal downward or back
placement of tongue
– Cleft palate
• Pathology: due to retrognathia which prevents
descent of the tongue into the oral cavity;
prevents secondary palate fusion
• Associated with a syndrome in 50-80% of
cases, most commonly Stickler & VCF
syndromes

Pierre-Robin Sequence
Figure 99.10 Robin sequence. This infant required a tracheostomy because of airway
compromise from severe micrognathia.

Velocardiofacial Syndrome
(Shprintzen Syndrome)
• Autosomal dominant, characterized by abnormal
facies, VPI, CLP, and cardiac anomalies
• Hemizygous microdeletion of 22q11
• Almond shaped palpebral fissures, deficient nasal
alae, tubuar nose with bulbous tip, small mouth
• Long face with vertical maxillary excess, malar
flatness, mandibular retrusion
• Palatal clefting ranges from submucus clefting to
overt wide cleft palate with hypernasality
• Cardiac anomalies in 80%, most commonly VSD;
other anomalies include right sided aortic arch,
tetralogy of Fallot, aortic valve disease
• Medial displacement of ICA’s present in up to 25% of
patients

Velocardiofacial Syndrome
(Shprintzen Syndrome)
Figure 99.11 Velocardiofacial syndrome. Broad nose, triangular face, palatal
incompetence.

Melkersen-Rosenthal Syndrome
(Chelitis Granulomatosa)
• Most cases of sporadic. Familial occurrences suggest an
autosomal dominant transmission
• Recurrent or persistent lip swelling, facial swelling, facial palsy
and furrowed tongue
– Swelling of the lips is usually of sudden onset, unilateral, or
bilateral. The upper lip is affected in most cases and may remain
swollen permanently. This occurs in 75% of patients.
– Histologically the swollen tissues exhibit chronic granulomatous
changes similar to sarcoidosis or tuberculosis
• Auditory and visual disturbances, swelling in the hands and
chest, blepharospasm, epiphora, and megacolon may be seen.
• The disease begins in childhood or early adulthood.
• It is considered a local immune response and vasomotor
disturbance affecting the vasa vasorum of the vessels supplying
the facial nerve and neighboring structures
Reference: Bailey’s Otolaryngology-Head & Neck Surgery

Discussion
1. Craniosynostosis
2. Cloverleaf skull syndrome

Craniosynostosis
• Primary craniosynostosis: a primary defect of
ossification at the sutures
• Secondary craniosynostosis: a failure of brain
growth, more commonly
• Syndromic craniosynostosis: display other body
deformities

Craniosynostosis
• The coronal suture separates the 2
frontal bones from the parietal
bones.
• The metopic suture separates the
frontal bones.
• The sagittal suture separates the 2
parietal bones.
• The lambdoid suture separates the
occipital bone from the 2 parietal
bones.
• The primary factor that keeps
sutures open is ongoing brain
growth.
• Normal skull growth occurs
perpendicular to each suture.

Primary craniosynostosis
• When 1 or more sutures fuse prematurely, skull growth
can be restricted perpendicular to the suture. If multiple
sutures fuse while the brain is still increasing in size,
intracranial pressure can increase.
• Cause: a primary defect in the mesenchymal layer
ossification in the cranial bones.
• A gene locus for single suture craniosynostosis has not
been identified.

Scaphocephaly - Early fusion of the sagittal suture

Ant. plagiocephaly - Early fusion of 1 coronal suture
Post. plagiocephaly - Early closure of 1 lambdoid suture

Brachycephaly - Early bilateral coronal suture fusion

Trigonocephaly - Early fusion of the metopic suture

Secondary craniosynostosis
• More frequent
• Early fusion of sutures due to primary failure of brain
growth
• Intracranial pressure usually is normal, and surgery
seldom is needed
• Intrauterine space constraints may play a role in the
premature fusion of sutures in the fetal skull. This
has been demonstrated in coronal craniosynostosis
• Microcephaly usually suggests a secondary
craniosynostosis

Secondary craniosynostosis
Endocrine
Hyperthyroidism, hypophosphatemia, vitamin D
deficiency, renal osteodystrophy, hypercalcemia, and
rickets
Hematologic disorders
Which cause bone marrow hyperplasia (eg, sickle cell
disease, thalassemia)
Inadequate brain growth
Microcephaly and its causes and shunted hydrocephalus

Treatment of Craniosynostosis
• Do not operate in patients without Increased ICP
until the shape of the head does not improve by
age 2-4 months, then the abnormality is unlikely
to resolve with age
• Cosmetic surgery is performed in infants aged
3-6 months in the author's practice