Common Otolaryngological Congenital Abnormalities Viet Pham, M.D. Lewis Hutchinson, M.D. Harold Pine, M.D. Shraddha Mukerji, M.D. University of Texas Medical Branch Grand Rounds Presentations November 22, 2010 Visual Synopsis of Classic Syndromes and Features http://www.explosm.net/comics
79
Embed
Common Otolaryngological Congenital · PDF fileCommon Otolaryngological Congenital Abnormalities Viet Pham, M.D. Lewis Hutchinson, M.D. Harold Pine, M.D. Shraddha Mukerji, M.D. ...
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
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
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.
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
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.
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.
Treacher Collins Syndrome Features
Downward slanting palpebral fissures
Lower eyelid colobomas
Hypoplastic supraorbital rims
Mandibular hypoplasia
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).
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
Mandibular hypoplasia
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
Mandibular hypoplasia
Microtia and preauricular tags/pits
Upper eyelid coloboma
Presenter
Presentation Notes
Mandibular hypoplasia via hypoplasia or rami and condyles
Type IIIAbsent ramus and nonexistent glenoid fossa
(Horgan, 1995)
Goldenhar Syndrome Classification Scheme
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
Goldenhar Syndrome Classification Scheme
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
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
Mandibular hypoplasia
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)
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.)
Stickler Syndrome Features
(Tolarova, 2009) (Pou
lson
, 200
4)
Midfacial hypoplasia
Long philtrum
Short upturned nose
Micrognathia
Stickler Syndrome Features
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
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
Waardenburg Syndrome Features
Flat nasal root
Heterochromia irides
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
Waardenburg Syndrome Features
Major
Heterochromia irides
White forelock
Dystopia canthorum
Congenital sensorineural hearing loss
Affected first-degree relative
Minor
Congenital leucoderma
Synophyrs
Broad high nasal root
Hypoplastic nasal alae
Premature graying hair
Waardenburg Syndrome Diagnosis
Major
Heterochromia irides
White forelock
Dystopia canthorum
Congenital sensorineural hearing loss
Affected first-degree relative
Minor
Congenital leucoderma
Synophyrs
Broad high nasal root
Hypoplastic nasal alae
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)
(courtesy of Dr. Hutchinson)
Presenter
Presentation Notes
Type 1 facial features: narrow nose, nasal bone hypoplasia, short philtrum, short and retropositioned maxilla
Waardenburg Syndrome Subtypes
Type 1
Full symptomatology
Facial asymmetry, abnormal 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(courtesy of Dr. Hutchinson)
Waardenburg Syndrome Subtypes
Type 1
Full symptomatology
Facial asymmetry, abnormal 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
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
(courtesy of Dr. Hutchinson)
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.
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.
Neurofibromatosis, Type 1 Features
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.
Neurofibromatosis, Type 2 Features
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
Affected first-degree relative
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
http://www.explosm.net/comics
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:
<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.
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.
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.
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.
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>.
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.