CRANIOFACIAL CRANIOFACIAL

ANOMALIESANOMALIES

BY:DR IMTIAZ AHMEDBY:DR IMTIAZ AHMEDBDS, FCPSBDS, FCPS

ORTHODONTICSORTHODONTICS

DiGeorge SyndromeDiGeorge Syndrome Genetic disorder due to microdeletion of Genetic disorder due to microdeletion of

Chromosome Chromosome 22q11.222q11.2 ( (tbx-1tbx-1 gene gene ))– The same genetic defect as VCF with different The same genetic defect as VCF with different

phenotypic expressionphenotypic expression Characterized by:Characterized by:

– Hypocalcemia (due to hypoplastic parathyroids)Hypocalcemia (due to hypoplastic parathyroids)– Immunodeficiency due to hypoplastic thymusImmunodeficiency due to hypoplastic thymus– Congenital heart defects of the outflow tracts (aorta Congenital heart defects of the outflow tracts (aorta

and pulmonary artery).and pulmonary artery).

•Reference: http://medicine.net

DiGeorge SyndromeDiGeorge Syndrome

Treacher-Collins Syndrome Treacher-Collins Syndrome (Mandibulofacial dysostosis)(Mandibulofacial dysostosis)

Autosomal dominant, 40% will have family history, other Autosomal dominant, 40% will have family history, other 60% new mutations60% new mutations

TCOF1TCOF1 gene found on chromosome 5q ( gene found on chromosome 5q (TREACLE TREACLE genegene ))

Malformation of 1st (& 2nd) branchial archesMalformation of 1st (& 2nd) branchial arches Otologic: Malformed ossicles, auricular deformity, aural Otologic: Malformed ossicles, auricular deformity, aural

atresia, CHL present 30% of time, occasional SNHLatresia, CHL present 30% of time, occasional SNHL– 50% will have hearing impairment from EAC and/or middle ear 50% will have hearing impairment from EAC and/or middle ear

malformationsmalformations Preauricular fistulas, mandibular and malar hypoplasia, Preauricular fistulas, mandibular and malar hypoplasia,

antimongoloid palpebral fissures, coloboma of the lower antimongoloid palpebral fissures, coloboma of the lower eyelids, may have cleft lip and palate, normal IQeyelids, may have cleft lip and palate, normal IQ

Treacher-Collins Syndrome Treacher-Collins Syndrome (Mandibulofacial dysostosis)(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)Apert (acrocephalosyndactyly) Autosomal dominant, most cases due to spontaneous Autosomal dominant, most cases due to spontaneous

mutationmutation Due to a mutation of Due to a mutation of FGFR-2FGFR-2 (Fibroblast Growth Factor (Fibroblast Growth Factor

Receptor) gene (Receptor) gene (10q2610q26 )) Common findings:Common findings:

– Craniosynostosis (pre-mature fusion of the cranial sutures)Craniosynostosis (pre-mature fusion of the cranial sutures)– Severe symmetrical syndactylySevere symmetrical syndactyly– Low-set earsLow-set ears– Cognitive function normal to severe mental retardationCognitive function normal to severe mental retardation– EyesEyes: down-slanting palpebrael fissures, Hypertelorism, Exophthalmos: down-slanting palpebrael fissures, Hypertelorism, Exophthalmos– Midface hypoplasiaMidface hypoplasia– Mandibular prognathismMandibular prognathism– Possible cleft palatePossible cleft palate– NoseNose: Parrot-beaked nose, possible Choanal Atresia: Parrot-beaked nose, possible Choanal Atresia– Syndactyly and cervical fusionSyndactyly and cervical fusion

Figure 99.4 Apert syndrome has the additional feature of syndactyly.

Reference: Bailey’s Otolaryngology-Head & Neck Surgery

Apert (acrocephalosyndactyly)Apert (acrocephalosyndactyly)

Crouzon SyndromeCrouzon Syndrome(Craniofacial Dysostosis)(Craniofacial Dysostosis)

Autosomal dominant, 50% due to spontaneous Autosomal dominant, 50% due to spontaneous mutations, complete penetrance, variable expresivitymutations, complete penetrance, variable expresivity

Due to mutation of Due to mutation of FGFR-2FGFR-2 (Fibroblast Growth Factor (Fibroblast Growth Factor Receptor) gene (Receptor) gene (10q2610q26 ))

Common findings:Common findings:– Craniosynostosis (pre-mature fusion of the cranial sutures)Craniosynostosis (pre-mature fusion of the cranial sutures)– HypertelorismHypertelorism– ExophthalmosExophthalmos– Midface hypoplasiaMidface hypoplasia– Mandibular prognathismMandibular prognathism– Parrot-beaked noseParrot-beaked nose– No Syndactyly or cervical fusionNo Syndactyly or cervical fusion– Cognitive function normal to severe mental retardationCognitive function normal to severe mental retardation

Crouzon SyndromeCrouzon Syndrome Coronal and sagittal Coronal and sagittal

sutures are most sutures are most commonly involved commonly involved

Cloverleaf skull is rare and Cloverleaf skull is rare and occurs in the most occurs in the most severely affected severely affected individuals. individuals.

Hydrocephalus Hydrocephalus (progressive in 30%) (progressive in 30%)

Crouzon SyndromeCrouzon 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 Branchiootorenal Syndrome (Melnick-Fraser Syndrome)(Melnick-Fraser Syndrome)

Autosomal dominantAutosomal dominant , involves 8q between D8S87 and , involves 8q between D8S87 and D8S165 (D8S165 (EYA1 geneEYA1 gene ))

Branchial cleft anomalies (63%): cysts or fistulaeBranchial cleft anomalies (63%): cysts or fistulae Otologic malformations: Otologic malformations:

– hearing loss (89%)hearing loss (89%)– preauricular pits (77%)preauricular pits (77%)– auricle abnormalities (41%)auricle abnormalities (41%)– ossicular & cochlear malformations ossicular & cochlear malformations – 2% of children with severe/profound SNHL2% of children with severe/profound SNHL

Renal Dysplasia (66%) Renal Dysplasia (66%) – agenesis, polycystic kidneys, duplicated ureters; renal agenesis, polycystic kidneys, duplicated ureters; renal

abnormalities identifiable on IVP or renal U/Sabnormalities identifiable on IVP or renal U/S

Branchiootorenal Syndrome Branchiootorenal Syndrome (Melnick-Fraser 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 SyndromeDown Syndrome Craniofacial Features:Craniofacial Features:

– BrachycephalyBrachycephaly– Flat occiputFlat occiput– Abnormal small earsAbnormal small ears– Upslanting palpebral fissuresUpslanting palpebral fissures– Epicanthic foldsEpicanthic folds– Short small noseShort small nose– Midface hypoplasiaMidface hypoplasia– Large fissured lipsLarge fissured lips– Large fissured tongueLarge fissured tongue– Dental abnormalitiesDental abnormalities– Short neckShort neck– Atlantoaxial subluxation & instabilityAtlantoaxial subluxation & instability

Down SyndromeDown Syndrome

Goldenhar Syndrome Goldenhar Syndrome (Oculoauriculovertebral spectrum)(Oculoauriculovertebral spectrum)

Characterized by unilateral facial asymmetry, unilateral Characterized by unilateral facial asymmetry, unilateral external & middle ear changes, vertebral malformationsexternal & middle ear changes, vertebral malformations

Ocular findings: upper lid colobomataOcular findings: upper lid colobomata Otologic findings: mildly deformed ears to anotia, EAC Otologic findings: mildly deformed ears to anotia, EAC

atresia, ossicular abnormalitiesatresia, ossicular abnormalities Underdevelopment of mandible, orbit, facial muscles, Underdevelopment of mandible, orbit, facial muscles,

also may have hemivertebrae of vertebral columnalso may have hemivertebrae of vertebral column Hemifacial macrosomia often placed in this categoryHemifacial macrosomia often placed in this category Most cases sporadic, some autosomal dominant Most cases sporadic, some autosomal dominant

reportedreported

Goldenhar Syndrome Goldenhar Syndrome (Oculoauriculovertebral spectrum)(Oculoauriculovertebral spectrum)

Reference: Bailey’s Otolaryngology-Head & Neck Surgery

Pierre-Robin SequencePierre-Robin Sequence Triad of:Triad of:

– RetrognathiaRetrognathia– GlossoptosisGlossoptosis– Cleft palateCleft palate

Pathology: due to retrognathia which prevents descent of Pathology: due to retrognathia which prevents descent of the tongue into the oral cavity; prevents secondary the tongue into the oral cavity; prevents secondary palate fusionpalate fusion

Associated with a syndrome in 50-80% of cases, most Associated with a syndrome in 50-80% of cases, most commonly Stickler & VCF syndromescommonly Stickler & VCF syndromes

GlossoptosisGlossoptosis is a medical condition and abnormality is a medical condition and abnormality which refers to the downward displacement or retraction which refers to the downward displacement or retraction of the of the tonguetongue

Pierre-Robin SequencePierre-Robin Sequence

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

DiscussionDiscussion1.1. CraniosynostosisCraniosynostosis

2.2. Cloverleaf skull syndromeCloverleaf skull syndrome

CraniosynostosisCraniosynostosis Primary craniosynostosisPrimary craniosynostosis: a primary defect of : a primary defect of

ossificationossification

Secondary craniosynostosisSecondary craniosynostosis: a failure of brain : a failure of brain growth, more commonlygrowth, more commonly

Syndromic craniosynostosisSyndromic craniosynostosis: display other body : display other body deformitiesdeformities

CraniosynostosisCraniosynostosis The coronal suture separates the 2 The coronal suture separates the 2

frontal bones from the parietal bones. frontal bones from the parietal bones. The metopic suture separates the The metopic suture separates the

frontal bones. frontal bones. The sagittal suture separates the 2 The sagittal suture separates the 2

parietal bones. parietal bones. The lambdoid suture separates the The lambdoid suture separates the

occipital bone from the 2 parietal occipital bone from the 2 parietal bones. bones.

The primary factor that keeps sutures The primary factor that keeps sutures open is ongoing brain growth. open is ongoing brain growth.

Normal skull growth occurs Normal skull growth occurs perpendicular to each suture.perpendicular to each suture.

Primary craniosynostosisPrimary craniosynostosis When 1 or more sutures fuse prematurely, skull growth can When 1 or more sutures fuse prematurely, skull growth can

be restricted perpendicular to the suture. If multiple sutures be restricted perpendicular to the suture. If multiple sutures fuse while the brain is still increasing in size, fuse while the brain is still increasing in size, intracranial intracranial pressurepressure can increase. can increase.

Cause: a primary defect in the mesenchymal layer Cause: a primary defect in the mesenchymal layer ossification in the cranial bones. ossification in the cranial bones.

A gene locus for single suture craniosynostosis has not A gene locus for single suture craniosynostosis has not been identified.been identified.

ScaphocephalyScaphocephaly - Early fusion of the - Early fusion of the sagittalsagittal suture suture

Ant. plagiocephaly - Early fusion of 1 coronal sutureAnt. plagiocephaly - Early fusion of 1 coronal suture

Post. plagiocephaly - Early closure of 1 lambdoid suturePost. plagiocephaly - Early closure of 1 lambdoid suture

Brachycephaly - Early bilateral coronal suture fusionBrachycephaly - Early bilateral coronal suture fusion

Trigonocephaly - Early fusion of the metopic sutureTrigonocephaly - Early fusion of the metopic suture

Secondary craniosynostosisSecondary craniosynostosis More frequentMore frequent Early fusion of sutures due to Early fusion of sutures due to primary failure of brain growth primary failure of brain growth Intracranial pressure usually is normal, and surgery seldom Intracranial pressure usually is normal, and surgery seldom

is neededis needed Intrauterine space constraints may play a role in the Intrauterine space constraints may play a role in the

premature fusion of sutures in the fetal skull. This has been premature fusion of sutures in the fetal skull. This has been demonstrated in coronal craniosynostosis demonstrated in coronal craniosynostosis

MicrocephalyMicrocephaly usually suggests a secondary usually suggests a secondary craniosynostosiscraniosynostosis

Secondary craniosynostosisSecondary craniosynostosis

EndocrineEndocrine Hyperthyroidism, hypophosphatemia, vitamin D deficiency, Hyperthyroidism, hypophosphatemia, vitamin D deficiency,

renal osteodystrophy, hypercalcemia, and ricketsrenal osteodystrophy, hypercalcemia, and rickets

Hematologic disordersHematologic disorders Which cause bone marrow hyperplasia (eg, sickle cell Which cause bone marrow hyperplasia (eg, sickle cell

disease, thalassemia)disease, thalassemia)

Inadequate brain growthInadequate brain growth Microcephaly and its causes and shunted hydrocephalusMicrocephaly and its causes and shunted hydrocephalus

Treatment of CraniosynostosisTreatment of Craniosynostosis Do not operate in patients without IICP until the Do not operate in patients without IICP until the

shape of the head does not improve by shape of the head does not improve by age 2-4 age 2-4 monthsmonths, then the abnormality is unlikely to resolve , then the abnormality is unlikely to resolve with agewith age

Cosmetic surgery is performed in infants Cosmetic surgery is performed in infants aged 3-6 aged 3-6 monthsmonths in the author's practice in the author's practice