Common Otolaryngological Congenital Abnormalities · PDF fileCommon Otolaryngological...

Common Otolaryngological

Congenital Abnormalities

Viet Pham, M.D.

Lewis Hutchinson, M.D.

Harold Pine, M.D.

Shraddha Mukerji, M.D.

The University of Texas Medical Branch

Department of Otolaryngology

November 22, 2010

Visual Synopsis of Classic Syndromes and Features

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Foreword and

Acknowledgements

Special appreciation to Dr. Hutchinson for his

assistance and contribution

Additional gratitude to Drs. Pine and Mukerji

All clinical photos are presented solely for educational

purposes

All other photos were obtained via a Google search unless

otherwise specified and are used without permission

Objective

Highlight typical features of congenital abnormalities

evaluated in the otolaryngology practice

Visual emphasis on classical presentation of commonly

encountered syndromes

Down Syndrome (Trisomy 21)

Extra chromosome 21

Meiotic nondisjunction in gamete formation

Mosaicism (1-2%)

Robertsonian translocation (2-3%)

Duplication (rare)

Increased risk with advanced maternal age

Most common cause of intellectual disability

Down Syndrome Features

Brachycephaly

Flat nasal bridge and occiput

Small, low-set ears

Macroglossia, glossoptosis

Upslanting palpebral fissures

Epicanthal folds

Brushfield spots

Simian crease

Sandal gap deformity of feet

Excessive nuchal folds

Mental retardation (courtesy of Dr. Hutchinson via Maria Blazo, M.D.)

Down Syndrome Features

(Do

urm

ishe

v, 2

00

9)

Simian crease Brushfield spots Sandal deformity

Excessive

nuchal folds

Upslanting palpebral fissure

Macroglossia,

glossoptosis

(Do

urm

ishe

v, 2

00

9)

(Do

urm

ishe

v, 2

00

9)

Microtic, low-set ears

Epicanthus

Brachycephaly

Flat nasal bridge,

hypoplastic maxilla

Down Syndrome Other Features

Muscular hypotonia

Strabismus

Congenital cataracts

Atrial or ventricular septal

defect

Gastroesophageal reflux

Duodenal stenosis or

atresia

Hirschsprung disease or

celiac disease

Seizures

Down Syndrome Prenatal Ultrasound

Absent nasal bones

First trimester (60-80%)

Second trimester (37-41%)

Hypoplastic nasal bones

Not useful as single marker in first

trimester

Best used with absent nasal bones in

second trimester (60-100%)

(Gonçalves, 2004)

Down Syndrome Otolaryngological Considerations

Tympanostomy tubes

Esophageal atresia,

tracheoesophageal fistula

Atlantoaxial instability

Obstructive sleep apnea

Hypothyroidism

Increased risk for malignancy

Acute lymphoblastic leukemia

Transient myeloproliferative disorder

Crouzon Syndrome (Craniofacial Dysostosis)

Autosomal dominant

Virtually complete penetrance

Mutation of fibroblast growth factor receptor II (FGFR2) on

chromosome 10

Affects first pharyngeal arch

Precursor maxilla

and mandible

Early fusion of face

and skull bones

(courtesy of Dr. Pine)

Crouzon Syndrome Features

Craniosynostosis

Exophthalmos

Hypertelorism

Strabismus

Psittichorhina

Hypoplastic maxilla

Mandibular

prognathism

(Jackson, 2009)

Crouzon Syndrome Features

Cranial synostosis Exophthalmos Hypertelorism

Strabismus

Hypoplastic maxilla

Mandibular

prognathism

Psittichorhina

(Jackso

n, 2

00

9)

Crouzon Syndrome Otolaryngological Considerations

Hearing loss in 1/3 of cases

Auricular misalignment

Ossicular fixation

Serous otitis media

Sensorineural and mixed hearing losses

Surgical craniofacial reconstruction

(http://candar.wordpress.com)

Crouzon Syndrome Otolaryngological Considerations


(Jackson, 2009)

Otolaryngological Congenital Abnormalites:

Visual Synopsis

Apert Syndrome (Acrocephalosyndactyly)

Autosomal dominant

Craniofacial abnormalities by FGFR2 mutations

Syndactyly by keratinocyte growth factor receptor (KGFR) mutations

Parents pass on to offspring

50% of the time

Sporadic mutation in 98%

Affects first pharyngeal arch

(Shah AR, Danahey DG. Distraction Osteogenesis of the Maxilla.

eMedicine 11 Feb 2009.)

Apert Syndrome Features

Craniofacial dysostosis

Hypoplastic maxilla

Frontal prominence

Syndactyly

Exophthalmos

Hypertelorism

Saddle nose, depressed

nasal bridge

Oral cavity

High-arched palate, cleft

palate

Dental abnormalities

(co

urt

esy o

f D

r. H

utc

hin

so

n)

Apert Syndrome Features

Craniofacial dysostosis

Hypoplastic

maxilla

Frontal

prominence

Syndactyly

Depressed

nasal bridge

Malocclusion

Ectopic eruption

Hypertelorism

(Ch

en

, 2

00

9)

Apert Syndrome Dr. Hutchinson’s mnemonic

Apert = Crouzon + Syndactyly

Apert Syndrome Otolaryngological Considerations

Conductive hearing loss

Chronic otitis media

Stapes fixation

Patent cochlear aqueduct

Surgical craniofacial reconstruction (Jackson, 2009)

Treacher Collins Syndrome (Mandibulofacial Dysostosis)

Also known as Franceschetti-Zwahlen-Klein syndrome

Autosomal dominant

TCOF1 gene on chromosome 5q

New mutation in up to 60%

Complete penetrance, variable expression

First and second pharyngeal arches,

grooves, and pouches

Treacher Collins Syndrome Features

Characteristic facial dysmorphia

Downward slanting palpebral fissures

Hypoplastic supraorbital rims

Malar hypoplasia

Mandibular hypoplasia

Auricular and middle

ear malformations

Lower eyelid coloboma

May have cleft palate

Normal intelligence

(Tolarova, 2009)


Downward slanting

palpebral fissures

Lower eyelid colobomas


Mandibular

hypoplasia Auricular malformation

Malar hypoplasia

(cou

rtesy o

f D

r. H

utc

hin

so

n)

(cou

rtesy o

f D

r. H

utc

hin

so

n)


Downward slanting

palpebral fissures

Lower eyelid colobomas


Mandibular

hypoplasia Auricular malformation

Malar hypoplasia Scant lower eyelashes

Treacher Collins Syndrome Otolaryngological Considerations

Hearing

Conductive hearing loss in 30%

Ossicular malformation

Microtia and/or canal atresia

Mastoid hypoplasia

Some sensorineural hearing loss and

vestibular dysfunction

Upper airway obstruction

(To

laro

va

, 2

00

9)

Treacher Collins Syndrome Otolaryngological Considerations


(Jackson, 2009)

Goldenhar Syndrome Oculoauriculovertebral Dysplasia

Diverse etiologies

In utero vascular disruption with hematoma

Disturbed neural crest cells at 30-45 days gestation

No single genetic locus

First and second branchial arch

Hemifacial microsomia

when no internal organ or

vertebral disruption

Goldenhar Syndrome Features



Microstomia

Epibulbar lipodermoids

Upper eyelid coloboma

Vertebral anomalies

(Ba

iley,

20

06

)

Goldenhar Syndrome Features


Epibulbar dermoid

Mandibular

hypoplasia

Microtia and preauricular tags/pits

Upper eyelid

coloboma

OMENS

Orbital distortion


Ear anomaly

Nerve (facial) involvement

Soft-tissue deficiency

“Plus” to include additional anomalies

Cardiac

Skeletal, limb

Pulmonary

Renal

Gastrointestinal

Goldenhar Syndrome Classification Scheme

An

de

rso

n P

J,

David

DJ.

Sp

ina

l a

no

malie

s in G

old

en

har

syn

dro

me

. C

left

Pa

late

-Cra

nio

facia

l Jo

urn

al 2

00

5; 4

2:4

77

-80.

Goldenhar Syndrome Classification Scheme: Mandible

Normal mandible (Horgan, 1995)


Type I

Smaller mandible but identifiable mandible

(Horgan, 1995)


Type II

Type IIA

Glenoid fossa is in an acceptable position

Functioning temporomandibular joint (TMJ) but abnormal shape and glenoid

fossa

(Horgan, 1995)


Type II

Type IIB

Abnormally placed TMJ cannot be incorporated into surgical

reconstruction

Functioning temporomandibular joint (TMJ) but abnormal shape and glenoid

fossa

(Horgan, 1995)


Type III

Absent ramus and nonexistent glenoid fossa

(Horgan, 1995)


Orbits

Ear

(Horgan, 1995)


Facial Nerve

Soft tissue defect

(Horgan, 1995)

Goldenhar Syndrome Otolaryngological Considerations

Hearing loss

More conductive than sensorineural

Ossicular abnormalities

Microtia

Aberrant facial nerve course


Pierre Robin Syndrome

Sequence of micrognathia, glossoptosis, and cleft palate

Syndrome reserved for multiple malformations by a single

etiology

Confusing classification, up to 14 definitions (Breugem 2009)

Possibly due to arrested intrauterine development

Mechanical

Neurological

Ontogenesis

(Tolarova, 2009)

Pierre Robin Syndrome Features

Cleft palate Glossoptosis

Retrognathia

Macroglossia and

ankloglossia uncommon

Micrognathia

(Jackson, 2009) (co

urt

esy o

f D

r. H

utc

hin

so

n)

(co

urt

esy o

f D

r. H

utc

hin

so

n)

Pierre Robin Syndrome Sequence


Between 7-11 weeks gestation

Mandible gets temporarily “stuck” between

clavicle and sternum

Oligohydramnios

Tongue remains high in oral cavity

Cleft palate results from failed closure of palatal shelves

U-shaped cleft palate (80%), can

have V-shaped (20%)

Typically no cleft lip

Pierre Robin Syndrome Otolaryngological Considerations

Airway compromise

Upper airway obstruction

Feeding, aspiration

Subglottic stenosis

Hearing loss

Otitis media most common

(60%)

Auricular malformation

Mixed hearing loss

Associated syndromes

Stickler (18-25%)

Velocardiofacial (7-15%)

Treacher Collins (5%)

Hemifacial microsomia (3%)

Mandibular “catch up” if

isolated sequence

(Tolarova, 2009)

Pierre Robin Syndrome Otolaryngological Considerations

Distraction osteogenesis

Intubation, tracheostomy

(To

laro

va

, 2

00

9)

Cleft palate repair

(courtesy of Dr. Hutchinson)

Stickler Syndrome

Autosomal dominant

Mutations of type II and XI collagen

COL2A1 gene on chromosome 12

COL11A1 and COL11A2 genes on chromosome 6

COL9A1 is rare recessive variant

Craniofacial, ocular, and

arthopathic features

Stickler Syndrome Features

“Flattened” face

Ocular findings

Musculoskeletal

abnormalities

Cleft palate

(cou

rtesy o

f D

r. H

utc

hin

so

n v

ia M

aria

Bla

zo

, M

.D.)


(Tolarova, 2009) (Po

uls

on

, 2

00

4)

Midfacial

hypoplasia

Long philtrum

Short upturned

nose

Micrognathia


Ocular

Myopia

Glaucoma

Retinal detachment

Cataracts

Musculoskeletal

Osteoarthritis

Joint hypermobility

Abnormal epiphyseal

development

Vertebral abnormalities

Scoliosis

Stickler Syndrome Otolaryngological Considerations

Hearing loss

Mild to moderate sensorineural hearing loss (SNHL) in 80%

Significant SNHL or mixed hearing loss in 15%

Conductive component secondary to eustachian tube dysfunction from

cleft palate

Ossicular abnormalities may be present

Pierre Robin sequence

Present in 25% of Stickler syndrome

Cleft palate

Micrognathia

(courtesy of Dr. Hutchinson via Maria Blazo, M.D.)

Waardenburg Syndrome

Autosomal dominant

Multiple genes

PAX3 (Types 1 and 3)

MITF, SNAI2 (Type 2)

EDN3, EDNRB, SOX10 (Type 4)

Autosomal recessive for Type 4

Variable penetrance

Hearing loss

Dystopia canthorum

Pigmentary abnormalities

(co

urt

esy o

f D

r. H

utc

hin

so

n)

Waardenburg Syndrome Features

Dystopia canthorum

Flat nasal root

Hypoplastic nasal alae

Synophyrs

Heterochromia irides

Isohypochromia irides

White forelock

Vitiligo

Cleft lip and palate (10%)

(Schwartz, 2010)


Flat nasal

root Heterochromia irides

Dystopia canthorum

Synophyrs

(Schwartz, 2010)

White forelock Hypoplastic alae Short philtrum

(cou

rtesy o

f D

r. H

utc

hin

so

n)

Isohypochromia irides


Major


White forelock

Dystopia canthorum

Congenital sensorineural

hearing loss

Affected first-degree relative

Minor

Congenital leucoderma

Synophyrs

Broad high nasal root


Premature graying hair

Waardenburg Syndrome Diagnosis

Major


White forelock

Dystopia canthorum

Congenital sensorineural

hearing loss


Minor

Congenital leucoderma

Synophyrs

Broad high nasal root


Premature graying hair

Diagnosis

2 major features

1 major features + 2 minor features

Waardenburg Syndrome Subtypes

Type 1

Full symptomatology

Facial asymmetry, dysmorphic facies

Type 2

No dystopia canthorum, white forelock less common

Sensorineural hearing loss, heterochomia irides

Type 3 (Klein-Waardenburg syndrome)

Similar to Type 1 but with skeletal anomalies and mental retardation

Rib aplasia, cystic sacrum, cutaneous syndactyly

Type 4 (Shah-Waardenburg syndrome)

Association with Hirschsprung disease

(Schwartz, 2010)



Type 1

Full symptomatology

Facial asymmetry, abnormal facies

Type 2










Type 1

Full symptomatology


Type 2





Rib aplasia, amyoplasia, cystic sacrum, cutaneous syndactyly




Type 1

Full symptomatology


Type 2








Waardenburg Syndrome Otolaryngological Considerations

Congenital sensorineural deafness

Typically not progressive

Hearing amplification

Cochlear implantation

Cleft lip or palate repair

Cosmetic considerations

Beckwith-Wiedemann

Syndrome

Imprinting defect at chromosome 11p15

Most cases are sporadic

Autosomal dominant familial inheritance in 15%

Most common overgrowth syndrome in infancy

Five common features

Macroglossia

Macrosomia

Midline abdominal wall defect

Ear pits/creases

Neonatal hypoglycemia


Beckwith-Wiedemann

Syndrome

Imprinting defect at chromosome 11p15

Most cases are sporadic

Autosomal dominant familial inheritance in 15%

Most common overgrowth syndrome in infancy

Five common features

Macroglossia

Macrosomia

Midline abdominal wall defect

Ear pits/creases


Beckwith-Wiedemann Features

Macroglossia

Macrosomia Ear pits/creases

Midline abdominal defect

(co

urt

esy o

f D

r. H

utc

hin

so

n

via

Ma

ria

Bla

zo

, M

.D.)


Major


Macroglossia

Macrosomia

Ear pits/creases

Adrenocortical cytomegaly

Renal abnormalities

Embryonal tumors

Cleft palate (rare)

Hemihyperplasia


Major


Macroglossia

Macrosomia

Ear pits/creases


Renal abnormalities

Embryonal tumors

Cleft palate (rare)

Hemihyperplasia

Minor


Polyhydramnios

Prematurity

Facial nevus flammeus

Hemangioma

Characteristic facies (i.e.

midface hypoplasia)

Cardiac anomalies

Diastasis recti

Advanced bone age

Beckwith-Wiedemann Diagnosis

Major


Macroglossia

Macrosomia

Ear pits/creases


Renal abnormalities

Embryonal tumors

Cleft palate (rare)

Hemihyperplasia

Minor


Polyhydramnios

Prematurity

Facial nevus flammeus

Hemangioma

Characteristic facies (i.e.

midface hypoplasia)

Cardiac anomalies

Diastasis recti

Advanced bone age

Diagnosis

At least 2 common features

3 major features

2 major features + 3 minor features

Beckwith-Wiedemann Otolaryngological Considerations

Macroglossia

Airway obstruction,

feeding difficulty

Less noticeable with age

Increased risk of malignancy

Wilms’ tumor

Hepatoblastoma

Surveillance

Abdominal ultrasound every 3 months until 8 years

Alpha-fetoprotein every 6 weeks until 4 years

Neurofibromatosis Type 1 (von Recklinghausen)

Peripheral neurofibromatosis

Autosomal dominant

Neurofibromin gene (NF1) on chromosome 17

Half result from de novo mutation

Variable expression

Better prognosis than Neurofibromatosis

Type 2

(Dahl, 2010)

(courtesy of Dr. Hutchinson via

Maria Blazo, M.D.)

Neurofibromatosis, Type 1 Features

Café au lait spots

Cutaneous neurofibromas

Plexiform neuromas

Lisch nodules

Axillary or perineum

freckling (Crowe sign)

Optic gliomas

Bone abnormalities


Cutaneous neurofibomas

Plexiform neuroma Optic glioma Lisch nodules Long bone bowing

Café au lait spots Axillary freckling

(Da

hl, 2

01

0)

(co

urt

esy o

f D

r. H

utc

hin

so

n

via

Ma

ria

Bla

zo

, M

.D.)

Neurofibromatosis, Type 1 Diagnosis

Six or more café au lait macules

Diameter larger than 5mm in prepubescent

Diameter larger than 15mm in adults

Two or more neurofibromas or one

plexiform neurofibroma

Axillary or inguinal freckling

Optic glioma

Two or more Lisch nodules

Distinctive osseous lesion

First-degree relative with condition

(Na

za

reth

, 2

01

0)

Neurofibromatosis Type 2

Central neurofibromatosis

Autosomal dominant

NF2 (Merlin) gene on chromosome 22

Approximately 10% of all individuals with

neurofibromatosis

Significant morbidity, decreased

lifespan

Paucity of café au lait spots and

Crowe sign

(Pletcher, 2010)


Café au lait spots

Schwannomas

Bilateral acoustic neuromas

Spinal cord

Nonvestibular

Subcapsular cataracts

Meningiomas

Ku

tz J

W J

r, R

ola

nd

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Neurofibromatosis, Type 2 Diagnosis

Bilateral vestibular schwannomas

Presumptive


Unilateral vestibular

schwannoma

Or two of the following:

Meningioma

Glioma

Schwannoma

Juvenile posterior subcapsular

or cortical cataract

Suggestive

Unilateral vestibular

schwannoma

Two of the following:

Meningioma

Glioma

Schwannoma

Juvenile posterior subcapsular

or cortical cataract

Or multiple meningiomas

Klippel-Feil Syndrome (Brevicollis, Wildervanck)

Cervical vertebral fusion

Type I – single level

Type II – multiple, noncontiguous segments

Type III – multiple, contiguous segments

Short, webbed neck and low hairline

Unclear etiology

Associated abnormalities

Sprengel deformity

Scoliosis

Facial asymmetry

Renal abnormalities

(Sullivan, 2009)

Other Syndromes Without Craniofacial Features

Usher

Hearing loss with defective inner ear

Type I – deafness and vestibular dysfunction

Type II – nonprogressive hearing loss and normal vestibular function

Type III – progressive hearing loss and half vestibular function

Progressive vision loss from retinitis pigmentosa

Pendred

Sensorineural hearing loss

Thyroid goiter

Jervell and Lange-Neilsen

Defective potassium channel from KCNQ1 and KCNE1

mutations

Sensorineural hearing loss and palpitations (long QT syndrome)

Yeah Yeah

Yeah

Conclusion

Many syndromes will

present to the

otolaryngologist

Warrant otolaryngological

intervention

Attention to coexisting

conditions

Many affected individuals

are aware of the social

stigma related to their

condition http://www.explosm.net/comics

References

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Lippincott, 2006. pp 1311-2,1380-6,2794.

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<http://emedicine.medscape.com/article/941723-overview>.

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Dahl AA, Grostern RJ. Neurofibromatosis-1. eMedicine 21 May 2010. Accessed 5 Nov 2010


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Nazareth MR, Helm TN. Neurofibromatosis. eMedicine 16 Jun 2010. Accessed 5 Nov 2010


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Orvidas LJ, et al. Hearing and otopathology in Crouzon syndrome. Layrngoscope 1999; 109:1372-5.

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Poulson AV, et al. Clinical features of type 2 Stickler syndrome. J Med Genet 2004; 41:e107.

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Pron G, et al. Ear malformation and hearing loss in patients with Treacher Collins syndrome. Cleft Palate

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Common Otolaryngological Congenital Abnormalities · PDF fileCommon Otolaryngological...

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