Common Otolaryngological Congenital Abnormalities Viet Pham ...

Common Otolaryngological Congenital Abnormalities

Viet Pham, M.D.Lewis Hutchinson, M.D.Harold Pine, M.D.Shraddha Mukerji, M.D.

University of Texas Medical BranchGrand Rounds PresentationsNovember 22, 2010

Visual Synopsis of Classic Syndromes and Features

http

://w

ww

.exp

losm

.net

/com

ics

http://www.explosm.net/comics

Foreword and Acknowledgements

Special appreciation to Dr. Hutchinson for his assistance and contributionAdditional gratitude to Drs. Pine and Mukerji

All clinical photos are presented solely for educational purposesAll 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

Presenter

Presentation Notes

I'm focusing more on a visually-intense presentation, inspired because people remember pictures of features as opposed to hoping that they'll remember certain symptoms after reading them in listed format in some textbook.

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

Presenter

Presentation Notes

First described in 1866 by Down; trisomy 21 discovered as the cause in 1959 by Lejeune and Jacobs et al. Considerable variability with mosaicism. Robertsonian translocation: Long arm of chromosome 21 gets attached to another chromosome (usually 14); affected individual is phenotypically normal but gamete formation gives a significant chance to create one with an extra chromosome 21— “familial Down syndrome”

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.)

Presenter

Presentation Notes

Round face Brushfield: speckled iris from aggregation of connective tissue Small ears with overfolded helix Macroglossia and glossoptosis also results from microgenia (small mouth), another feature epicanthal fold, or epicanthus, is a skin fold of the upper eyelid covering the inner corner (medial canthus) of the eye Sandal gap deformity: Large space between 1st and 2nd toes Mental retardation is generally mild (IQ 50-70) to moderate (IQ 35-50). Mosaic Down syndrome may actually have IQ 10-30 points higher.

Down Syndrome Features

(Dou

rmis

hev,

200

9)

Simian creaseBrushfield spots Sandal deformityExcessive nuchal folds

Upslanting palpebral fissure

Macroglossia, glossoptosis

(Dou

rmis

hev,

200

9)

(Dou

rmis

hev,

200

9)

Microtic, low-set ears

Epicanthus

Brachycephaly

Flat nasal bridge, hypoplastic maxilla

Presenter

Presentation Notes

People normally have “upslanting palpebral fissures,” but they are more prominent in Down syndrome.

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)

Presenter

Presentation Notes

Combination of hypoplastic and absent nasal bones in second trimester can detect 60-100% of Down syndrome prenatally

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

Presenter

Presentation Notes

OSA usually from enlarged palatine and lingual tonsils, adenoids, and glossoptosis obstructing the airway. Need PETs for ROM and CHL secondary to COM. Hypothyroidism typically from Hashimoto’s. A high incidence of atlantoaxial instability of the cervical spine usually from laxity of the transverse ligament between the odontoid process of the C2 vertebra and the posterior aspect of the anterior arch of the C1 vertebra; the C1 can sublux anteriorly on C2 and compress the spinal cord—especially during neck extension and head “lifting” that occurs with laryngoscopy, worse with head rotation

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)

Presenter

Presentation Notes

First described by the French physician, Octave Crouzon, in 1912.

Crouzon Syndrome Features

Craniosynostosis

Exophthalmos

Hypertelorism

Strabismus

Psittichorhina

Hypoplastic maxilla

Mandibular prognathism

(Jackson, 2009)

Caused by a mutation in the fibroblast growth factor receptor II, located on chromosome 10this syndrome affects the first branchial (or pharyngeal) arch, which is the precursor of the maxilla and mandibleWhat occurs in the disease is that an infant's skull and facial bones, while in development, fuse early or are unable to expand. Thus, normal bone growth cannot occur. Fusion of different sutures leads to different patterns of growth of the skull. hypoplastic maxilla: insufficient growth of the midfacemandibular prognathism: chin appears to protrude despite normal growth of mandible and gives the effect of the patient having a concave faceMental retardation possible if premature closure of the cranial suture linesPsittichorhina: beak-like nose

Presenter

Presentation Notes

Caused by a mutation in the fibroblast growth factor receptor II, located on chromosome 10 this syndrome affects the first branchial (or pharyngeal) arch, which is the precursor of the maxilla and mandible What occurs in the disease is that an infant's skull and facial bones, while in development, fuse early or are unable to expand. Thus, normal bone growth cannot occur. Fusion of different sutures leads to different patterns of growth of the skull. hypoplastic maxilla: insufficient growth of the midface mandibular prognathism: chin appears to protrude despite normal growth of mandible and gives the effect of the patient having a concave face Mental retardation possible if premature closure of the cranial suture lines Psittichorhina: beak-like nose

http://en.wikipedia.org/wiki/First_branchial_arch

http://en.wikipedia.org/wiki/Maxilla

http://en.wikipedia.org/wiki/Mandible

Crouzon Syndrome Features

Cranial synostosis Exophthalmos Hypertelorism

Strabismus

Hypoplastic maxilla

Mandibular prognathism

Psittichorhina

(Jac

kson

, 200

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)

http://candar.wordpress.com/

Crouzon Syndrome Otolaryngological Considerations


(Jackson, 2009)

Presenter

Presentation Notes

Left: Appearance following frontosupraorbital advancement with simultaneous maxillary advancement at the Le Fort III level. Right: Postoperative distraction position. The dental occlusion is in an overcorrected position to allow for posterior relapse.

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.)

Presenter

Presentation Notes

First described by the French physician, Eugene Apert, in 1906.

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

(cou

rtesy

of D

r. H

utch

inso

n)

Presenter

Presentation Notes

Common dental abnormalities include high-arched palate, pseudomandibular prognathism (appearing as mandibular prognathism), a narrow palate, and crowding of the teeth. Some upper airway obstruction with OSA is common with abnormal craniofacial structure. Can have normal intelligence or mental retardation with CNS malformation.

Apert Syndrome Features

Craniofacial dysostosis

Hypoplastic maxilla

Frontal prominence

Syndactyly

Depressed nasal bridge

Malocclusion Ectopic eruption

Hypertelorism

(Che

n, 2

009)

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)

Presenter

Presentation Notes

Child is 5 days after frontosupraorbital and maxillary advancement.

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

Presenter

Presentation Notes

This syndrome was named after the eminent British ophthalmologist Edward Treacher Collins (1862-1932), who described the essential features of this syndrome in a paper in 1900. However, some features of this syndrome were probably first described by Thomson and Toynbee in 1846-1847 and later by Berry (1889), who is usually given credit for its discovery. High prevalence of new mutations suggest also an intrauterine insult etiology (weeks 6-8 of gestation). There has been some reported recessive forms.

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)

Presenter

Presentation Notes

Lateral 1/3 of lower eyelid affected Upper eyelid coloboma seen in Goldenhar; symmetric facies and bilateral colobomas distinguish this from Goldenhar Abnormal skull base. Mandible also has hypoplastic condyle, short ramus and mandibular body, anteriorly displaced TMJ. Skull bones maintain their original anatomy as the child grows. Nose is usually NORMAL SIZE but appears large due to surrounding facial hypoplasia, but do have a flatter nasofrontal angle and underdeveloped lower nasal cartilage Cleft palate in 1/3 Mental retardation in just 5%, most developmental delay secondary to hearing loss.



Lower eyelid colobomas



Auricular malformation

Malar hypoplasia

(cou

rtesy

of D

r. H

utch

inso

n)

Presenter

Presentation Notes

Plain radiographs reveal the malar hypoplasia, “tear drop”– shaped orbits and partial or complete absence of the zygomatic arches. In severe cases, there is absence of the lateral wall and the floor of the orbits (i.e., a clefting of the inferolateral orbit extending into the spheno-maxillary [inferior orbital] fissure).

(cou

rtesy

of D

r. H

utch

inso

n)



Lower eyelid colobomas




Malar hypoplasiaScant 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

(Tol

arov

a, 2

009)

Presenter

Presentation Notes

The stapes is usually NORMAL but can be monopedal and/or ankylosed footplate. Mastoid region often demonstrates agenesis or poor pneumatization.

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

Presenter

Presentation Notes

Present in 1-2% of families, suggestive of an autosomal dominant familial pattern in some.

Goldenhar Syndrome Features

Hemifacial microsomia


Microstomia

Epibulbar lipodermoids

Upper eyelid coloboma

Vertebral anomalies

(Bai

ley,

200

6)

Presenter

Presentation Notes

Lower eyelid coloboma in Treacher Collins Parotid is often affected (agenesis or displaced) Mental retardation in 5-15% Congenital heart defects in 5-58%

Goldenhar Syndrome Features

Hemifacial microsomia

Epibulbar dermoid


Microtia and preauricular tags/pits

Upper eyelid coloboma

Presenter

Presentation Notes

Mandibular hypoplasia via hypoplasia or rami and condyles

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

And

erso

n P

J, D

avid

DJ.

Spi

nal a

nom

alie

s in

Gol

denh

arsy

ndro

me.

Cle

ft P

alat

e-C

rani

ofac

ial J

ourn

al20

05; 4

2:47

7-80

.

Goldenhar Syndrome Classification Scheme: Mandible

Normal mandible(Horgan, 1995)


Type ISmaller mandible but identifiable mandible

(Horgan, 1995)


Type II

Type IIAGlenoid fossa is in an acceptable position

Functioning temporomandibular joint (TMJ) but abnormal shape and glenoid fossa

(Horgan, 1995)


Type II

Type IIBAbnormally placed TMJ cannot be incorporated into surgical

reconstruction

Functioning temporomandibular joint (TMJ) but abnormal shape and glenoid fossa

(Horgan, 1995)


Type IIIAbsent ramus and nonexistent glenoid fossa

(Horgan, 1995)


Orbits

Ear

(Horgan, 1995)

Presenter

Presentation Notes

ORBIT 0. normal 1. abnormally sized eye 2up. inferior displacement of eye 2dn. superior displacement 3. abnormal size and position EAR 0. normal Mild hypoplasia and cupping of all structures External auditory canal atresia with variably hypoplastic concha Malpositioned lobule with absent auricle; lobular remnant usually displaced anteroinferiorly


Facial Nerve

Soft tissue defect

(Horgan, 1995)

Presenter

Presentation Notes

FACIAL NERVE 0. normal Temporal and zygomatic branch involvement Buccal +/- mandibular +/- cervical involvement Complete nerve SOFT TISSUE DEFECT 0. normal Minimal Moderate Severe

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)

Presenter

Presentation Notes

Lannelongue and Menard first described Pierre Robin syndrome in 1891 in a report on 2 patients with micrognathia, cleft palate, and retroglossoptosis (downward displacement or retraction of tongue). In 1926, Pierre Robin published the case of an infant with the complete syndrome. Breugem and Courtemanche (2009) illustrated the confusion regarding the classification of Robin sequence. They surveyed (via questionnaires) numerous aspects, among them, the difference between "retrognathia" and "micrognathia" and whether the cleft type (ie, "U-shaped" versus "V-shaped") had any influence in the decision-making process. A Pubmed literature review of the 50 most recent articles about Robin sequence was also included. The results were confusing. The questionnaires revealed 14 different definitions, and the Pubmed review of 50 publications gave 15 different opinions regarding Robin sequence. Three pathophysiological theories exist to explain the occurrence of Pierre Robin sequence. (1) The mechanical theory: This theory is the most accepted. The initial event, mandibular hypoplasia, occurs between the 7th and 11th week of gestation. This keeps the tongue high in the oral cavity, causing a cleft in the palate by preventing the closure of the palatal shelves. This theory explains the classic inverted U-shaped cleft and the absence of an associated cleft lip. Oligohydramnios could play a role in the etiology since the lack of amniotic fluid could cause deformation of the chin and subsequent impaction of the tongue between the palatal shelves. (2) The neurological maturation theory: A delay in neurological maturation has been noted on electromyography of the tongue musculature, the pharyngeal pillars, and the palate, as has a delay in hypoglossal nerve conduction. The spontaneous correction of the majority of cases with age supports this theory. (3) The rhombencephalic dysneurulation theory: In this theory, the motor and regulatory organization of the rhombencephalus is related to a major problem of ontogenesis.

Pierre Robin Syndrome Features

Cleft palate

Glossoptosis

Retrognathia

Macroglossia and ankloglossia uncommon

Micrognathia

(Jackson, 2009) (cou

rtesy

of D

r. H

utch

inso

n)

(cou

rtesy

of D

r. H

utch

inso

n)

Presenter

Presentation Notes

Micrognathia: small mandible; Retrognathia: posterior displacement of mandible Macroglossia and ankloglossia uncommon (10-15%) CNS defects include: speech delay,epilepsy, neurodevelopmental delay, hypotonia, hydrocephalus

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%)


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)

Presenter

Presentation Notes

Upper airway obstruction includes obstructive sleep apnea. Cleft palate hampers feeding/nursing and requires a special bottle (with a hole on top to allow effortless delivery of milk) or Haberman Feeder. No mandibular “catch up” if other associated syndromes (i.e. Treacher Collins, Stickler). Catch-up is not complete in isolated cases. The proportion of cases that are isolated Robin sequence varies in different studies. Hanson and Smith found that 25% of Robin sequence cases had specific syndromes, another 35% had multiple anomalies without a specific recognized syndrome, and only 40% had isolated Robin sequence. Another study found that 74% of cases were isolated Robin sequence. Cummings: 80% associated with other syndromes.

Pierre Robin Syndrome Otolaryngological Considerations

Distraction osteogenesis

Intubation, tracheostomy

(Tol

arov

a, 2

009)

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

Presenter

Presentation Notes

In 1965, Stickler described a family followed at the Mayo Clinic for five generations that segregated syndromic features, including myopia, clefting, and hearing loss. On the basis of criteria set forth by Snead and Yates, the diagnosis of SS requires (1) congenital vitreous anomaly, and (2) any three of myopia with onset before age 6 years, rhegmatogenous retinal detachment or paravascular pigmented lattice degeneration, joint hypermobility with abnormal Beighton score, SNHL (audiometric confirmation), or midline clefting. 2/3 to 3/4 of affected individuals will have the COL2A1 mutation. No ocular symptoms with COL11A2 mutation.

Stickler Syndrome Features

“Flattened” face

Ocular findings

Musculoskeletal abnormalities

Cleft palate

(cou

rtesy

of D

r. H

utch

inso

n vi

a M

aria

Bla

zo, M

.D.)


(Tolarova, 2009) (Pou

lson

, 200

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

Presenter

Presentation Notes

Myopia = near sightedness Typical clinical history = (+) cleft palate, (+) family history of osteoarthritis

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

(cou

rtesy

of D

r. H

utch

inso

n)

Presenter

Presentation Notes

Waardenburg syndrome (WS) is named after the Dutch ophthalmologist who, in 1947, first described a patient with hearing loss, dystopia canthorum (ie, lateral displacement of the inner canthi of the eyes), and retinal pigmentary differences. In 1951, after identifying other patients with similar symptoms, Waardenburg defined the syndrome now classified as Waardenburg syndrome type 1 (WS1). Findings in WS1 include hearing loss, dystopia canthorum, and pigmentary abnormalities of the hair, skin, and eyes. These genes are most likely related to melanocyte differentiation (i.e. melanocytes are required in the stria vascularis for normal cochlear function; pigmentation).

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)

Presenter

Presentation Notes

Synophyrs = hypertrichosis of medial eyebrows Blepharophimosis = convergent strabismus with reduced visibility of the medial sclera Comprises 1-7% of hereditary deafness. Diminshed vestibular function in 75%. Can have premature graying


Flat nasal root


Dystopia canthorum

Synophyrs

(Schwartz, 2010)

White forelock Hypoplastic alae Short philtrum

(cou

rtesy

of D

r. H

utch

inso

n)

Isohypochromia irides

Presenter

Presentation Notes

Widely spaced medial canthi is present in ALL cases. Synophyrs = hypertrichosis of medial eyebrows Comprises 1-7% of hereditary deafness. Diminshed vestibular function in 75%. Cleft lip and palate in 10%. Can have premature graying and vitiligo


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)


Presenter

Presentation Notes

Type 1 facial features: narrow nose, nasal bone hypoplasia, short philtrum, short and retropositioned maxilla


Type 1

Full symptomatology

Facial asymmetry, abnormal facies

Type 2







Association with Hirschsprung disease(courtesy of Dr. Hutchinson)


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

Presenter

Presentation Notes

Comprises 1-7% of hereditary deafness. Diminshed vestibular function in 75%.

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


Presenter

Presentation Notes

In 1964, Hans-Rudolf Wiedemann reported a familial form of omphalocele with macroglossia in Germany. In 1969, J. Bruce Beckwith of Loma Linda University, California, described a similar series of patients. Originally, Professor Wiedemann coined the term EMG syndrome to describe the combination of congenital exomphalos, macroglossia, and gigantism. Over time, this constellation was renamed Beckwith-Wiedemann syndrome (BWS). Beckwith-Wiedemann syndrome is the most common overgrowth syndrome in infancy. Imprinting: gene expression differs by whether they are maternal or paternal in origin; one is typically active and the other silent.

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

(cou

rtesy

of D

r. H

utch

inso

n vi

a M

aria

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

Presenter

Presentation Notes

Risk of malignancy appears greater in children (<4yrs), not so much in adulthood. Wilms’: nephroblastoma

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.)

Presenter

Presentation Notes

50% de novo mutation implies a lack of family history is fairly common NF1 has better prognosis because it has less CNS tumors compared to NF2, but there is a higher incidence of malignant peripheral nerve sheath tumors (MPNSTs), neurosarcomas, and gastrointestinal stromal tumors.

Neurofibromatosis, Type 1 Features

Café au lait spots

Cutaneous neurofibromas

Plexiform neuromas

Lisch nodules

Axillary or perineum freckling (Crowe sign)

Optic gliomas

Bone abnormalities

Presenter

Presentation Notes

Cutaneous neurofibromas typically enlarge and increase in number with time. “button hole sign”: neurofibromas are soft, but can be pushed deeper into the dermis on palpation Lisch nodules are hamartomas of the iris that are asymptomatic (usually seen with slit-lamp) but help confirm the diagnosis. 80% NF1 are axillary freckling. Bone abnormalities typically involve tibial pseudoarthrosis, long bone bowing, or orbital defects (pulsatile exophthalmos) secondary to sphenoid wing dysplasia.


Cutaneous neurofibomas

Plexiform neuroma Optic glioma Lisch nodulesLong bone bowing

Café au lait spots Axillary freckling

(Dah

l, 20

10)

(cou

rtesy

of D

r. H

utch

inso

n vi

a M

aria

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

(Naz

aret

h, 2

010)

Presenter

Presentation Notes

Diagnosis made if at least 2 of the following are fulfilled.

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)

Presenter

Presentation Notes

Merlin is thought to be a tumor-suppresant gene on central and peripheral nervous systems. Can be a difficult diagnosis due to lack of CNS involvement at an early age.


Café au lait spots

Schwannomas

Bilateral acoustic neuromas

Spinal cord

Nonvestibular

Subcapsular cataracts

Meningiomas

Kut

zJW

Jr,

Rol

and

PS, I

saac

son

B. S

kull

base

, aco

ustic

ne

urom

a(v

estib

ular

sch

wan

nom

a): m

ultim

edia

. eM

edic

ine

24 S

ep 2

009.

Acc

esse

d 5

Nov

201

0 <h

ttp://

emed

icin

e.m

edsc

ape.

com

/arti

cle/

8828

76-m

edia

>.

Presenter

Presentation Notes

Dumbbell-shaped spinal cord schwannomas Nonvestibular: CN III, V, IX, X, XI

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)

Presenter

Presentation Notes

First described by Maurice Klippel and Andre Feil independently in 1912. Sprengel: malformed and displaced scapula There may be some autosomal dominance with fusion of C2-3 and autosomal recessiveness with fusion of C5-6

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)

YeahYeah

Yeah

Presenter

Presentation Notes

Retinitis pigmentosa: progressive degeneration of retinal cells; typically first with rod cells (night vision and loss of peripheral vision) Pendred syndrome may have occasional hypothyroidism

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


References

Admiraal RJ, et al. Hearing impairment in Stickler syndrome. Adv Otorhinolaryngol 2002; 61:216-23.Bailey BJ, Johnson JT, Newlands SD, eds. Head and Neck Surgery – Otolaryngology, 4th Ed. Philadelphia:

Lippincott, 2006. pp 1311-2,1380-6,2794.Breugem CC, Courtemanche DJ. Robin sequence: clearing nosologic confusion. Cleft Palate Craniofac J

2010; 47:197-200.Chen H. Apert syndrome. eMedicine 2 Sep 2009. Accessed 12 Oct 2010

<http://emedicine.medscape.com/article/941723-overview>.Chen H. Crouzon syndrome. eMedicine 10 Sep 2009. Accessed 12 Oct 2010

<http://emedicine.medscape.com/article/942989-overview>.Chen H. Down syndrome. eMedicine 22 Mar 2010. Accessed 31 Oct 2010

<http://emedicine.medscape.com/article/943216-overview>.Crawford AH, Schorry EK. Neurofibromatosis update. J Pediatr Orthop 2006; 26:413-23.Dahl AA, Grostern RJ. Neurofibromatosis-1. eMedicine 21 May 2010. Accessed 5 Nov 2010

<http://emedicine.medscape.com/article/1219222-overview>.DeBaun MR, et al. Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann

syndrome with cancer and birth defects. Am J Hum Genet 2002; 70:604-11.DeBaun MR, Tucker MA. Risk of cancer during the first four years of life in children from The Beckwith

Wiedemann Syndrome Registry. J Pediatr 1998; 132:398-400.DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of

neurofibromatosis 1 in children. Pediatrics 2000; 105(3 Pt 1):608-14.

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




References

Dourmishev AL, Janniger CK. Down syndrome. eMedicine 1 Jul 2009. Accessed 4 Nov 2010 <http://emedicine.medscape.com/article/1113071-overview>.

Dourmishev LA, Janniger CK. Waardenburg syndrome. eMedicine 2 Jun 2009. Accessed 30 Oct 2010 <http://emedicine.medscape.com/article/1113314-overview>.

Elliott M, et al. Clinical features and natural history of Beckwith-Wiedemann syndrome: presentation of 74 new cases. Clinical Genetics 1994; 46:168-74.

Farrer LA, et al. Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium. Am J Hum Genet 1992; 50:902-13.

Ferry RJ. Beckwith-Wiedemann syndrome. eMedicine 15 Apr 2010. Accessed 23 Oct 2010 <http://emedicine.medscape.com/article/919477-overview>.

Flint PW, et al, eds. Cummings Otolaryngology: Head and Neck Surgery, 5th Ed. Philadelphia: Mosby Elsevier, 2010. ch 147, 184.

Gould HJ, Caldarelli DD. Hearing and otopathology in Apert syndrome. Archives of Otolaryngology 1982; 108:347-9.

Gonçalves LF, Espinoza J, Lee W, et al. Phenotypic characteristics of absent and hypoplastic nasal bones in fetuses with Down syndrome: description by 3-dimensional ultrasonography and clinical significance. J Ultrasound Med 2004; 23:1619-27.

Handzic J, et al. Hearing levels in Pierre Robin syndrome. Cleft Palate Craniofac J 1995; 32:30-6.Hata T, Todd MM. Cervical spine considerationswhen anesthesizing patients with Down syndrome.

Anesthesiology 2005; 102:680-5.




References

Heike CL, Hing AV. Craniofacial microsomia review. Gene Review. Eds. Pagon RA, et al. 19 Mar 2009. Accessed 23 Oct 2010 <http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=m-hfm-ov>.

Horgan JE, et al. OMENS-plus: analysis of craniofacial and extracraniofacial anomalies in hemifacial microsomia. Cleft Palate Craniofac J 1995; 32:405-12.

Jackson IT, Malhotra G. Congenital syndromes. eMedicine 2 Jul 2009. Accessed 12 Oct 2010 <http://emedicine.medscape.com/article/1280034-overview>.

Jakobsen LP, et al. The genetic basis of the Pierre Robin Sequence. Cleft Palate Craniofac J 2006; 43:155-9.Lee KJ, ed. Essential Otolaryngology – Head and Neck Surgery, 9th Ed. New York: McGraw Hill, 2008. pp

139-59.Liu XZ, Newton VE, Read AP. Waardenburg syndrome type II: phenotypic findings and diagnostic criteria. Am

J Med Genet 1995; 55:95-100.Nazareth MR, Helm TN. Neurofibromatosis. eMedicine 16 Jun 2010. Accessed 5 Nov 2010

<http://emedicine.medscape.com/article/1112001-overview>.Nowak CB. Genetics and hearing loss: a review of Stickler syndrome. J Commun Disord 1998; 31:437-54.Orvidas LJ, et al. Hearing and otopathology in Crouzon syndrome. Layrngoscope 1999; 109:1372-5.Peterson-Falzone SJ, Hardin-Jones MA, Karnell MP. Cleft Palate Speech, 4th Ed. St. Louis: Mosby, 2010.Pletcher BA. Neurofibromatosis, type 2. eMedicine 3 Mar 2010. Accessed 5 Nov 2010

<http://emedicine.medscape.com/article/1178283-overview>.Poulson AV, et al. Clinical features of type 2 Stickler syndrome. J Med Genet 2004; 41:e107.

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=m-hfm-ov



References

Pron G, et al. Ear malformation and hearing loss in patients with Treacher Collins syndrome. Cleft Palate Craniofac J 1993; 30:97-103.

Robin NH, Falk MJ, Haldeman-Englert CR. FGFR-related craniosynostosis syndromes. Gene Review. Eds. Pagon RA, et al. 27 Sept 2007. Accessed 19 Oct 2010 <http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=craniosynostosis>.

Saenz RB. Primary care of infants and young children with Down syndrome. Am Fam Physician 1999; 59:381- 90,392,395-6.

Samartzis DD, Herman J, Lubicky JP. Classification of congenitally fused cervical patterns in Klippel-Feil patients: epidemiology and role in the development of cervical spine-related symptoms. Spine 2006; 31:F798-804.

Samartzis D, Lubicky JP, Herman J. Symptomatic cervical disc herniation in a pediatric Klippel-Feil patient: the risk of neural injury associated with extensive congenitally fused vertebrae and a hypermobile segment. Spine 2006; 31:F335-8.

Sangkhathat S, et al. Novel mutation of Endothelin-B receptor gene in Waardenburg-Hirschsprung disease. Pediatr Surg Int 2005; 21:960-3.

Schwartz RA, Jozwiak S, Krantz I. Waardenburg syndrome. eMedicine 4 Jun 2010. Accessed 24 Oct 2010 <http://emedicine.medscape.com/article/950277-overview>.

Spivey PS, Bradshaw WT. Recognition and management of the infant with Beckwith-Wiedemann syndrome. Adv Neonatal Care 2009; 9:279-84.

Sullivan AJ. Klippel-Feil syndrome. eMedicine 23 Jun 2009. Accessed 5 Nov 2010 <http://emedicine.medscape.net/article/1264848-diagnosis>.

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=craniosynostosis


References

Tewfik TL, Trinh N, Teebi AS. Pierre Robin Syndrome. eMedicine 4 Mar 2010. Accessed 21 Oct 2010 <http://emedicine.medscape.com/article/844143-overview>.

Tolarova MM. Pierre Robin Malformation. eMedicine 25 Mar 2009. Accessed 21 Oct 2010 <http://emedicine.medscape.com/article/995706-overview>.

Tolarova MM, Wong GB, Varma S. Mandibulofacial dysostosis. eMedicine 24 Nov 2009. Accessed 17 Oct 2010 <http://emedicine.medscape.com/article/946143-overview>.

Verheij JB, et al. Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature. Eur J Paediatr Neurol 2006; 10:11-7.

Watanabe A, et al. Epistatic relationship between Waardenburg syndrome genes MITF and PAX3. Nat Genet 1998; 18:283-6.




Date post:	04-Jan-2017
Category:	Documents
Upload:	vodung
View:	227 times
Download:	3 times

Common Otolaryngological Congenital Abnormalities Viet Pham ...

Documents