2. DiGeorge Syndrome
⢠Genetic disorder due to microdeletion of
Chromosome 22q11.2 (tbx-1 gene)
â The same genetic defect as VCF with different
phenotypic expression
⢠Characterized by:
â Hypocalcemia (due to hypoplastic parathyroids)
â Immunodeficiency due to hypoplastic thymus
â Congenital heart defects of the outflow tracts
(aorta and pulmonary artery).
â˘Reference: http://medicine.net
3. 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
â 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
4. Treacher-Collins Syndrome
(Mandibulofacial dysostosis)
Figure 99.12 Treacher Collins syndrome. Zygomatic and mandibular hypoplasia, lower lid
colobomas, and downslanting palpebral fissures.
Reference: Baileyâs Otolaryngology-Head & Neck Surgery
5. 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:
â Craniosynostosis (pre-mature fusion of the cranial sutures)
â Severe symmetrical syndactyly
â Low-set ears
â Cognitive function normal to severe mental retardation
â Eyes: down-slanting palpebrael fissures, Hypertelorism,
Exophthalmos
â Midface hypoplasia
â Relative Mandibular prognathism
â Possible cleft palate
â Nose: Parrot-beaked nose, possible Choanal Atresia
â Syndactyly and cervical fusion
6. Figure 99.4 Apert syndrome has the additional feature of
syndactyly.
Reference: Baileyâs Otolaryngology-Head & Neck Surgery
Apert (acrocephalosyndactyly)
7. 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:
â Craniosynostosis (pre-mature fusion of the cranial sutures)
â Hypertelorism
â Exophthalmos
â Midface hypoplasia
â Relative Mandibular prognathism
â Parrot-beaked nose
â No Syndactyly
â Cognitive function normal to severe mental retardation
8. 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%)
9. 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
10. Branchiootorenal Syndrome
(Melnick-Fraser Syndrome)
⢠Autosomal dominant, involves 8q between D8S87 and
D8S165 (EYA1 gene)
⢠Branchial cleft anomalies (63%): cysts or fistulae
⢠Otologic malformations:
â hearing loss (89%)
â preauricular pits (77%)
â auricle abnormalities (41%)
â ossicular & cochlear malformations
â 2% of children with severe/profound SNHL
⢠Renal Dysplasia (66%)
â agenesis, polycystic kidneys, duplicated ureters; renal
abnormalities identifiable on IVP or renal U/S
11. 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: Baileyâs Otolaryngology-Head & Neck Surgery
12. Down Syndrome
⢠Craniofacial Features:
â Brachycephaly
â Flat occiput
â Abnormal small ears
â Upslanting palpebral fissures
â Epicanthic folds
â Short small nose
â Midface hypoplasia
â Large fissured lips
â Large fissured tongue
â Dental abnormalities
â Short neck
â Atlantoaxial subluxation & instability
13. 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
15. Pierre-Robin Sequence
⢠Triad of:
â Retrognathia - abnormal posterior positioning of
either of the jaws
â Glossoptosis - abnormal downward or back
placement of tongue
â 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
16. Pierre-Robin Sequence
Figure 99.10 Robin sequence. This infant required a tracheostomy because of airway
compromise from severe micrognathia.
17. 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 ICAâs present in up to 25% of
patients
19. 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
â 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.
â 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: Baileyâs Otolaryngology-Head & Neck Surgery
21. 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
22. 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.
23. 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.
28. 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
29. Secondary craniosynostosis
ďŻEndocrine
Hyperthyroidism, hypophosphatemia, vitamin D
deficiency, renal osteodystrophy, hypercalcemia, and
rickets
ďŻHematologic disorders
Which cause bone marrow hyperplasia (eg, sickle cell
disease, thalassemia)
ďŻInadequate brain growth
Microcephaly and its causes and shunted hydrocephalus
30. 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