Syndromes, Cleft lip + palate, VPI

Question 1

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Regarding the Tensor Veli Palatini, discuss:
1. Origin
2. Course of muscle
3. Attachment
4. Blood Supply - 2
5. Innervation - 1
6. Function - 2

Answer 1

ORIGIN:
- Situated in the pterygoid fossa between the medial and lateral pterygoid plates (between medial pterygoid muscle and medial pterygoid plate)
- 75% arises from the Outer side of cartilaginous portion of the eustachian tube, with the remainder from the bone between the sphenoid spine and the scaphoid fossa
- Tapers inferiorly from this relatively wide origin

COURSE OF MUSCLE:
- Muscle tapers inferiorly from the relatively wide origin
- Runs lateral to the hamulus and then turns at a right angle anterior to it
- Tendon occupies most of the length of the hamulus

INSERTION:
- Muscle fibres converge inferiorly into the tendon that courses around the medial side of the pterygoid hamulus of sphenoid bone
- Runs at a right angle and inserts into the palatine aponeurosis (comprises anterior third of soft palate)
- Palatine aponeurosis pierces buccinator en route to soft palate
- Eventually attaches to the posterior margin of the hard palate, palatine crest, and tendon of the opposite side

BLOOD SUPPLY:
- Greater palatine branch of internal maxillary artery
- Ascending palatine branch of facial artery

INNERVATION:
V3 (mandibular branch of trigeminal nerve)

FUNCTION:
1. Tenses soft palate
2. Opens Eustachian tube during swallowing

https://entokey.com/wp-content/uploads/2016/05/9781604065862_c011_f001.jpg

Kevan Peds #50

Question 2

Regarding the Levator Veli Palatini, discuss:
1. Origin
2. Course of muscle
3. Attachment
4. Blood Supply
5. Innervation
6. Function

Answer 2

Contributes to main part of the soft palate

ORIGIN:
- Superior portion: Undersurface of the apex of the petrous bone
- Inferior portion: Inner surface of the cartilaginous portion of the eustachian tube
- Occupies intermediate 40% of the length of the soft palate

COURSE:
- Travels inferomedially to the palatine aponeurosis

INSERTION:
- Fibers spread out in the soft palate where they blend with those of the opposite side

ARTERIAL BLOOD SUPPLY:
- Ascending palatine artery branch from facial artery
- Descending palatine breanch of maxillary artery

VENOUS BLOOD SUPPLY:
- Pterygoid plexus via ascending/descending palatine veins that drain to IJV

INNERVATION:
Pharyngeal plexus (IX, X, cervical plexus)

FUNCTION:
1. Acts as sling to pull velum in posterosuperior direct (when contracts)
2. Elevates the velum (major elevator)
3. Positions the velum

Kevan Peds #50

Question 3

Regarding the Palatoglossus, discuss:
1. Origin
2. Course of muscle
3. Attachment
4. Innervation
5. Function

Answer 3

Most superficial muscle on the oral aspect of the soft palate

ORIGIN:
- Anterior surface of soft palate

COURSE:
- Curving inferior to the lateral margin of the tongue, raises the mucous membrane to produce the palatoglossal arch (anterior pillar of tonsil)

INSERTION:
- Lateral tongue

Blood supply - ascending pharyngeal and ascending palatine

INNERVATION: Pharyngeal Plexus (IX, X, cervical plexus)

FUNCTION:
1. Elevates tongue upward and backward to constrict the pillars
2. Lowers velum
3. Positions velum

Janfaza, kenhub

Question 4

Regarding the Palatopharyngeus, discuss:
1. Origin
2. Course of muscle
3. Attachment
4. Innervation
5. Function

Answer 4

Most superficial muscle on the pharyngeal surface of the soft palate

ORIGIN:
- Some of its fibers originate from anterior aspect of the soft palate
- Includes some sphincteric fibers that are related to the superior pharyngeal constrictor

COURSE:
- Anterior and posterior layers blend with the uvula and levator veli palatini
- These join laterally to form a muscle bundle inferiorly into the pharynx to form the palatopharyngeal arch (posterior tonsillar pillar)

INSERTION:
- Posterior border of thyroid cartilage

INNERVATION: Pharyngeal Plexus (IX, X, cervical plexus)

FUNCTION:
1. Adducts posterior tonsillar pillars
2. Constructs the pharyngeal isthmus
3. Narrows the velopharyngeal orifice
4. Raises the larynx
5. Lowers the pharynx
6. Positions the velum

Question 5

Regarding the muscularis uvulae, discuss:
1. Origin
2. Course of muscle
3. Attachment
4. Innervation
5. Function

Answer 5

ORIGIN:
- Palatal aponeurosis in a circumscribed area posterior to hard palate
- Located just deep to the posterior upper layer of the palatopharyngeus muscle

COURSE:
- Comprises of longitudinally directed fibers that pass inferiorly into the uvula

INSERTION:
- Uvula

INNERVATION: Pharyngeal Plexus (IX, X, cervical plexus)

FUNCTION:
1. Provides bulk to dorsal surface of the soft palate

Question 6

List the muscles of the soft palate

Answer 6

1. Tensor Veli Palatini
2. Levator Veli Palatini
3. Palatoglossus
4. Palatopharyngeus
5. Muscularis Uvulae

Kevan Peds #50

Question 7

Regarding the Superior Constrictor, discuss:
1. Origin
2. Attachment
4. Innervation
5. Function

Answer 7

ORIGIN:
- Lower third of the posterior margin of the internal pterygoid plate and its hamular process

INSERTION:
- Pharyngeal median raphae

INNERVATION:
- Pharyngeal plexus (IX, X, cervical plexus)

FUNCTION:
1. Medial movement of the lateral apsects of the pharyngeal walls
2. High levels of activity related to laughter
3. Draws velum posteriorly

Question 8

List all the actions of the soft palate muscles

Answer 8

1. Palatoglossus + palatopharyngeus = lowers soft palate and narrow the faucial isthmus
2. Muscularis Uvulae draws the uvula superiorly and anteriorly
3. Levator veli palatini muscles raises and retracts the soft palate to bring it in touch with the posterior pharyngeal wall and opens the eustachian tube
4. Tensor veli palatini muscle tenses and lowers the soft palate and opens the eustachian tube

Question 9

Describe the motor and sensory innervation of the palate

Answer 9

MOTOR INNERVATION
- Tensor veli palatini = V3 branch via otic ganglion
- All other muscles are innervated by ascending branches from the pharyngeal plexus (supplied by CNX via cranial or bulbar rootlets of CN XI)

SENSORY INNERVATION: Branches of the pterygopalatine (sphenopalatine) ganglion.
1. Lesser Palatine nerves
- Exit via the lesser palatine foramina near the posterior margin of the hard palate, posterior to the greater palatine foramen
- Supply the soft palate and neighboring area around the upper pole of the tonsil both for general sensation and for taste

2. Maxillary nerve (V2)
   - Palatine branches from the pterygopalatine ganglion join the greater (anterior) palatine nerve through the greater palatine (pterygopalatine) canal in the lateral wall of the nose, accompanying the greater palatine artery
   - In the canal, this nerve supplies twigs to the inferoposteriior portion of the nasal cavity
   - The nerve and vessels exit from the greater palatine foramen (posterior palatine foramen) at the level of the third upper molar tooth
   - The nerve branches supplies the hard palate and the palatine gingiva. The terminal branches and a branch from the pterygopalatine ganglion innerve a small region just behind the incisor teeth
3. Fibers of the posterior cranial nerves or upper spinal nerves
   - Reach the pterygopalatine ganglion via the nerve of the pterygoid canal (vidian nerve)

Question 10

What is the predominant vasculature of the palate?

Answer 10

Main artery = Descending palatine artery (branch of Internal Maxillary artery), which branches into:
- Greater Anterior palatine artery (main branch) - Passes anteriorly over the lateral surface of the hard palate at its junction with the alveolar process. Then anteriorly runs superiorly through incisive (anterior palatine) canal to communicate in the nasal cavity with septal branches of the SPA
- Lesser palatine artery (anastomose posteriorly with the additional arteries below)

Additional arteries:
1. Ascending pharyngeal (runs above the upper border of the superior pharyngeal constrictor)
2. Facial (enters palate from below and laterally)
3. Dorsal lingual artery (enters palate from below and laterally)

VEINS:
- Drains into the pterygoid plexus or pharyngeal venous plexus
- External palatine vein passes inferiorly in the bed of the tonsil before it pierces the superior pharyngeal constrictor to terminate in the facial or pharyngeal vein

Question 11

What is Passavant’s Ridge?

Answer 11

Passavant’s Ridge = Mucosal ridge raised by fibers of the palatopharyngeus along the posterior wall of the nasopharynx
- Formed by the contraction of the superior constrictor muscle during swallowing
- Contraction of soft palate brings it in contact with ridge to separate naso- from oropharynx during speech and swallowiing

Superior constrictor and palatopharyngeus together

Present in 20-30% of normal population
Presence of absence does NOT correlate with development or degree of VP

Vancouver 502

Question 12

What are the possible velopharyhngeal closure patterns, and what are the incidences of each? 4

Answer 12

Closure patterns describe the orientation of the residual gap on incomplete closure of the velopharynx.

1. CORONAL (55%): Palate moves posteriorly, no movement of lateral or posterior walls
2. SAGITTAL (10-15%): Lateral wall closure - side to side movement only
3. CIRCULAR (10-20%): Palate and lateral wall movement, but overall incomplete closure
4. CIRCULAR WITH PASSAVANT’S RIDGE (15-20%): Palate and lateral wall movement, with presence of Passavant’s ridge

Question 13

Describe the four main types of possible velopharyngeal dysfunction and the risk factors for each

Answer 13

1. OBSTRUCTION
   - Hyponasality (e.g. adenoid hypertrophy)
2. INADEQUACY: INCOMPETENCE (impaired motor control; secondary to neurologic dysfunction)
   - Stroke
   - Jugular foramen or vagus tumors - affecting VII, IX, X
   - Muscular dystrophies
   - Myasthenia gravis
   - TBI
   - Down syndrome
   - Velocardiofacial syndrome (22q11 deletion)
3. INADEQUACY: INSUFFICIENCY (inadequate soft tissue/anatomic tissue)
   - Cleft palate
   - Submucous cleft palate
   - Occult submucous cleft palate
   - Enlarged tonsils
   - Congenital short palate
   - Post-adenoidectomy (1/1500 adenoidectomies)
4. INADEQUACY: MISLEARNING/FUNCTIONAL (Functional-Psychological problem)
   - Hearing loss
   - Cultural
   - Misarticulation
   - Imitating parental patterns
   - Habitual (learned during perior prior to VPI repair)
   - Phonemic (speech impediment)

Question 14

What are the causes of velopharyngeal insufficiency?

Answer 14

1. History of cleft palate
2. Submucous cleft
3. Deep pharynx (cranial base or cervical spine anomalies)
4. Irregular adenoids
5. Enlarged tonsils
6. Neurological injury
7. Syndromes: Down (hypotonia), VCF
8. Complication of adenoidectomy, maxillary advancement, UPPP, or resection of nasopharyngeal tumors

Question 15

What are 4 clinical signs of a submucous cleft palate? What are the 3 common syndromic associations?

Answer 15

1. Muscular diastasis of the soft palate
2. Zona pellucida (a bluish tint to the tissue along the midline of the soft palate)
3. Notch in hard palate (secondary to absence of posterior vomerine spine)
4. Bifid uvula

ASSOCIATIONS:
1. Stickler’s
2. Velocardiofacial
3. Treacher collins

Question 16

What is an occult submucous cleft palate?
How is it diagnosed? List 2 signs

Answer 16

Occult Submucous cleft palate = Absence/dehiscent of muscularis uvulae

Can only diagnose on scope:
- Very mild A-P gap
- Best seen with bubbling with plosives which should have complete closure (e.g. p, t, k)
- Uvula and palate look and feel normal on regular exam

Question 17

Which sounds require an open vs. closed velum. Which sounds require higher pharyngeal constriction vs. lower pharyngeal constriction?

Answer 17

OPEN: (not affected by VPI)
- M
- N
- Ng

CLOSED: Plosives (worsens with VPI)
- P
- B
- T
- s
- Sh
- Z
- H

HIGHER PHARYNGEAL CONSTRICTION:
- i
- U

LOWER PHARYNGEAL CONSTRICTION:
- A

Question 18

What is the quoted risk of VPI post-adenoidectomy? When should surgery be considered?

Answer 18

• Up to 100% will have some degree of transient VPI secondary to splinting from pain, but usually only lasts days-weeks ~6 weeks (warn and ask parents)
• 1/1500 will have long term VPI requiring some degree of intervention (e.g. SLP)
• DO NOT consider surgery until > 1 year post-operatively

Question 19

Regarding velopharyngeal insufficiency (VPI), discuss:
1. Key history, symptoms, and physical exam points

Answer 19

KEY HISTORY QUESTIONS:
1. Voice intelligibility
2. Nasal reflux
3. OSA
4. Cardiac problems (clues to Velocardiofacial)
5. Cleft palate
6. Previous adenoidectomy
7. Infant hypotonia/poor feeding
8. Severity of symptoms

SYMPTOMS:
1. Nasal fluid reflux
2. Nasal turbulence
3. Hypernasal voice
4. OM/otorrhea wiith tubes
5. Facial grimace during speech (physical effort to close velopharynx)

Question 20

How do you workup VPI?

Answer 20

WORK-UP/INVESTIGATIONS:
1. FNL:
- Closure patterns
- Pulsations in pharyngeal walls (look for medialized carotids)

2. SLP:
   - Nasometry (measuring ratio of sound intensity between the nose and mouth, while voicing standardized phrases)
   - Nasal occlusion test (humming “mm” while occluding the nose)
   - Mirror fogging test
   - Speech videofluoroscopy
   - Speech nasal endoscopy
   - Aerodynamic assessmet (two probes - oral and nasal. Pressure of airflow through the nose and mouth are measured during specific tasks)

• McKay-Kummer Simpliified Nasometric Assessment Procedure (SNAP test)
• Age 3-9yo: Repeat syllables
• Age >9yo: Read nasal passages, rainbow passage, zoo passage

3. Genetics
   - r/o 22q11 deletion (especially for kids presenting with no cause for VPI (FISH)
4. MRI/MRA if genetic testing +Ve
   - R/o medialized carotids

Question 21

How do you manage VPI?

Answer 21

TREATMENT:
1. Speech therapy
- Not helpful for anatomic causes
- Teaching moderate compensatory mechanisms (correct articulation, improve intelligibility)
- Correct mislearned behaviour
- Strengthening palatal muscles if tone is an issue

2. Palate prosthesis or obturator
   - Usually not well tolerated, still allows air/fluid escape
3. Biofeedback with nasometry
4. CPAP (strengthens palate)
5. Surgery (see card on surgical options)

Question 22

Describe the SNAP test, how are the results calculated and what is abnormal?

Answer 22

SNAP Test = McKay-Kummer Simplified Nasometric Assessment Procedure
- Test to identify hypo vs. hypernasality

Equation = (nasal airflow) / (nasal + oral airflow)

3+ SD above mean = HYPERNASAL

Question 23

Describe the surgical options for velopharyngeal insufficiency and what their common indications are.

Answer 23

1. INJECTION (bulking)
   - For mild VPI, e.g. post-adenoidectomy
   - Small air gaps (1-3mm)
2. SUPERIORLY BASED PHARYNGEAL FLAP (most common)
   - For A-P closure problems, adynamic palate
   - Useful for larger AP gaps
3. FURLOW (Z-PLASTY & RE-ORIENTATION OF SOFT PALATE MUSCLES)
   - Palate repair, adding a small amount of length to soft palate
   - Useful for small AP gaps (1-3mm) in addition to cleft palate
   - Cleft palate
   - Submucous cleft
4. SPHINCTER (Elevation of palatopharyngeal muscles, sewn into posterior pharyngeal wall - DYNAMIC flap)
   - Lateral wall closure problems
   - Circular closure problems
   - Huge A-P gaps (too big for superior flap)
5. TWO-FLAP PALATOPLASTY

Can combine flaps if needed to achieve best result
If presence of large tonsils/adenoids, may restrict repair - remove 3-6 months prior

Chapter 188 Cummings

Question 24

√Regarding 22q11 deletions, discuss:
1. What are the types of syndromes? List 2 common and 4 others.
2. Genetics and Inheritance?
3. What are the classic features?

Answer 24

SYNDROMES:
1. Velocardiofacial Syndrome (VCF)
- Autosomal dominant, variably expressed and penetrance
- Deletions in chromosome 22q11 leads to abnormal development of pharyngeal arches
2. DiGeorge = VCF + thymic aplasia (= T-cell immunodeficiency)
3. Kabuki
4. Opitz
5. Cayler
6. Shprintzen

GENETICS & INHERITANCE:
- Autosomal Dominant
- Gene: 22q11.2 deletion

Mnemonic for features: CATCH-22
C: Cardiac defects
A: Abnormal/adenoid facies
T: Thymic aplasia
C: Cleft palate
H: Hypocalcemia

FEATURES:
1. 100% palate defects or VPI (1/3 cleft, 1/3 submucous cleft, 1/3 occult submucous cleft
2. 75% cardiac defects (e.g. interrupted aortic arch, truncus arteriosus, TOF, etc.)
3. 25% medialized internal carotid arteries
4. Facies: long face, malar flattening, long philtrum, thin upper lip, long narrow nose, small ears
5. 75% conductive hearing loss
6. 20% Vascular ring (right aortic arch)
7. 15% can also have pierre robin sequence
8. 15% parathyroid aplasia (hypocalcemia)
9. Anterior glottic webs
10. Psychological/development delay

Question 25

Differentiate Primary bone vs. secondary bone

Answer 25

Primary Bone = Temporary, random composition of collagen fibres (immature, woven bone)

Secondary Bone = Orderly collagen fibers & osteoblasts (mature, lamellar bone)

Question 26

Describe the 2 mechanisms of osteogenesis

Answer 26

1. ENDOCHONDRAL BONE FORMATION
   - Hypertrophy of cartilage cells –> surrounding matrix calcifies –> forms cuff of perichondral bone –> vascular bud migrates into central cartilaginous cavity (forming marrow)
   - Therefore, in these locations bone does NOT regrow if fractured (can only form fibrous tissue scar)
2. INTRAMEMBRANOUS BONE FORMATION
   - Mesenchymal cells differentiate into osteoblasts –> accumulate in areas of bone formation –> forms osteoid (primary bone callus) –> matures & ossifies to secondary bone

Question 27

What sites in the head/neck are formed of endochondral bone?

Answer 27

“ME SO POSHI”

M: Mastoid
E: Ethmoid
S: Sphenoid
O: Occipital
P: Petrous Temporal bone
O: Otic capsule
S: Styloid process
H: Hyoid bone
I: Inferior turbinate

All others are intramembranous formation

Question 28

Describe the 3 main craniofacial growth centres and how they are formed. When are they typically formed by?

Answer 28

A. NEUROCRANIUM
1. CALVARIA (Superior skull: frontal, parietal, temporal, ethmoid, sphenoid)
- Initially separated by fontanelles to allow for brain growth
- Growth largely completed by 4 years
- Fuse along suture lines in adulthood

2. BASOCRANIUM (Inferior skull/skull base: occiput, temporal, ethmoid, sphenoid)
   - Grows in AP direction along midline synchondroses (cartilaginous joint where bones join around hyaline cartilage/bone united to hyaline cartilage)
   - 95% completed by 10 years

B. NASOMAXILLARY COMPLEX
1. Nasal, lacrimal, maxillary, zygomatic, pterygoid, and vomer bones
- Growth of middle cranial fossa pushes NMC anterio-inferior
- Growth of orbits & nose causes NMV to grow vertically
– Orbit growth complete by 7 years
– Nasal growth complete by 12-15 years
- Sinuses:
– Maxillary & Ethmoid present at birth –> completed by 16 years
– Frontal appears at 5 years –> completed by 16 years
– Sphenoid appears at 6 years –> continue growth into adulthood

C. MANDIBLE
- Midline symphysis fuses at 1 year
- After midline symphysis, followed by AP & condylar growth (to maintain TMJ relationship)
- Complete by 18 years (F), 25 years (M)

Question 29

List a differential for causes of abnormal craniofacial growth - 7

Answer 29

1. CONGENITAL
   - Anatomic: Pierre Robin Sequence
   - Genetic: Syndromes, Craniosynostoses (skull fused at birth), cleft palate, etc.
2. INFECTIOUS
   - Adenoid facies/AFRS
3. IATROGENIC (surgery)
   - Mandibular/dental surgery
   - Rhinoplasty
   - Sinus surgery
4. TRAUMA
   - Facial fractures
5. ENDOCRINE
   - Growth hormone (Excess, depletion)
6. NEOPLASTIC
   - Benign tumors (e.g. JNA, fibrous dysplasia)
   - Malignant tumors
   - Treatment: XRT

Question 30

Describe the embryological formation of the palate

Answer 30

1. PRIMARY PALATE: Between incisive foramina - premaxilla, lip, nasal tip, columella, includes alveolar ridge
   - 6 weeks GA: Medial and lateral nasal prominences fuse with maxillary prominences –> forms nasal bone, nostrils, upper lip –> confluence = primary palate
2. SECONDARY PALATE: Bilateral lateral shelves from incisive foramen to uvula bilateral
   - 8 weeks GA: lateral shelves fuse in midline to form secondary palate
3. Primary + Secondary palates fuse from anterior to posterior, completed by 12 weeks GA

Kevan Peds Question 65

Question 31

Describe the epidemiology of cleft lip and palate.
Which is more common?
Which has sex predilection?
Is there an ethnicity predilection?
What % is syndromic?

Answer 31

- Most common H/N congenital abnormality
- Second most common malformation after club foot

CLEFT LIP (isolated)
- 1/1000 live births
- Ethnicities: Native Americans, Asians, Non-hispanic whites
- Lowest among Africans
- M>F (2:1)

CLEFT PALATE (isolated)
- 1/2000 live births
- Does not vary among ethnic groups
- F > M (2:1) - Fusion of the palatine shelves occurs 1 week later in girls than boys therefore felt to have higher incidence of Cleft palate
- Usually associated with syndrome (50%)
- L > R
- Unilateral > Bilateral

- 70% of Cleft lip and palate together is non-syndromic
50% of cleft palate alone is non-syndromic

Question 32

What are the suspected etiology for cleft lip and palate?

Answer 32

Most common = unkonwn

1. Genetic
2. Environmental (folate deficiency, maternal diabetes, amniotic band syndrome, teratogens - ethanol, thalidomide, vitamin A)

Associated heart anomalies ≤ 10%
Genetic concordance is 25-40% monozygotic twins; 3-5% dizygotic twins

Question 33

What is the risk of having a baby with cleft lip±palate or cleft palate alone in the following situations?

Answer 33

A. No family history of cleft lip or cleft palate
1. Cleft Lip ± Cleft palate = 0.1%
2. Cleft Palate = 0.04%

B. Unaffected parents with one previous affected child
1. Cleft Lip ± Cleft palate = 4%
2. Cleft Palate = 2%

C. Two previously affected children
1. Cleft Lip ± Cleft palate = 9%
2. Cleft palate = 1%

D. One affected parent
1. Cleft Lip ± Cleft palate = 4%
2. Cleft palate = 6%

E. One affected parent and one previously affected child
1. Cleft Lip ± Cleft palate = 17%
2. Cleft palate = 15%

Kevan Peds 66#

Question 34

Describe the classification of a cleft lip

Answer 34

A. Unilateral or bilateral
B. Complete or incomplete
C. Right or left (if unilateral)

• Complete Cleft Lip involves the entire vertical thickness of the upper lip, often associated with alveolar cleft because lip and primary palate share same embryologic origin
• Incomplete cleft lip involves only a portion of the vertical height of the lip, with a variable segment of continuity across the cleft region (may be muscular diastasis with intact overlying skin, or wide cleft with thin band of skin crossing it)

IOWA CLASSIFICATION (1990):
1. Group I: Clefts of lip only
2. Group II: Clefts of palate only
3. Group III: Clefts of lip, alveolus and palate
4. Group IV: Clefts of lip and alveolus
5. Group V: Misc

Cummings Chapter 188
Vancouver 500

Question 35

What is Simonart’s Band?

Answer 35

Bridge or bar of lip tissue of variable size that crosses a cleft lip gap
- Usually consists of skin only, although muscle fibers may also lie within the band
- Essentially a band of orbicularis oris that is left intact
- In cleft repair, these fibers must be reapproximated

Question 36

Describe the classification of a cleft palate

Answer 36

A. Unilateral (right or left) or bilateral
B. Complete or incomplete
C. Primary or Secondary palate (ie. anterior to or posterior to incisive foramen)

Unilateral cleft of secondary palate = palatal process of the maxilla on one side is fused with nasal septum

Bilateral complete cleft of the secondary palate = no point of fusion between the maxilla and nasal septum

Complete cleft of entire palate = both primary and secondary palate and includes one or both sides of the premaxilla/alveolar arch, frequently involves a cleft lip

Isolated cleft palate = usually involves only the secondary palate and has varying degrees of severity

Least severe incomplete cleft = submucous cleft palate

Cummings Chapter 188

Question 37

Describe the Veau classification of cleft palate

Answer 37

I - isolated cleft of soft palate
II - cleft of soft and hard palates, extending to incisive foramen
III - Complete unilateral cleft of the lip, alveolus, and soft/hard palate
IV - complete bilateral clefts of the lip, alveolus, soft/hard palates

Pasha’s

Question 38

How is cleft lip and palate typically diagnosed prenatally?

Answer 38

Prenatal ultrasound can diagnosis cleft lip and palate (more reliable for cleft lip)
- Can be made as early as 18 weeks
- Over 15% of fetuses will have other anomalies

Question 39

What are some environmental causes of cleft palate?

Answer 39

Development of CL/P or isolated cleft palate is a multifactorial process:
1. Multiple risk factors
2. Genetic mutations
3. Family history of orofacial clefting
4. Maternal diseases and behaviours
5. Fetal exposures to teratogenic medications, and nutritional deficiencies or excesses

TOXIN/DRUG causes:
1. Phenytoin
2. Vitamin A derivatives (Retinoids/Retinoic acid)
3. Valproic Acid
4. Dioxin
5. Thalidomide
6. EtOH/Smoking in 1st trimester
7. Folic acid antagonists
8. Steroids in 1st trimester
9. Isotretinoin

MATERNAL:
1. Diabetes mellitus
2. Maternal obesity
3. Insufficient folic acid
4. Amniotic band syndrome

Maternal age is NOT a risk factor

Question 40

Discuss the anatomy of a unilateral cleft lip deformity. What are some of the other anatomical alterations associated with the unilateral cleft lip?

Answer 40

ANATOMY OF A UNILATERAL CLEFT LIP DEFORMITY:
- Normal orbicularis oris muscle forms a complete sphincter around the oral cavity
- All CL deformities have muscular deficiencies and irregularities of varying degrees that lead to the abnormal appearance and function of the lip and mouth
- Muscle fibers in CL deformities run in an inferior-to-superior direction along the margins of the cleft
- Muscle fibers in CL insert into the columella medially, and along the nasal alae laterally
- For CL repair, these fibers must be detached from their insertions and reoriented horizontal direction to bridge the cleft and create a muscular sliing around the entire circumference of oral cavity

ASSOCIATED ANATOMICAL ALTERATIONS WITH UNILATERAL CLEFT LIP:
- Nasal tip widened, deflected toward non-cleft side, and under projected
- Lateral crus of lower lateral cartilage is caudally displaced on cleft side, typically flattened and shorter
- Middle crus of lower lateral cartilage are shorter and separated from the non-cleft middle crus
- Columella is shorter than normal on cleft side and lies on the non-cleft side (unopposed action of intact orbicularis muscle)
- Nostril on cleft size is horizontally oriented rather than normal vertical orientation (flattened)
- Nasal septum and dorsum deflected to the non-cleft side
- Caudal nasal septum frequently dislocated from the vomerine groove and displaced into the non-clefted nostril
- Alar base on the cleft side is displaced laterally, inferiorly, and posteriorly
- Deficiency in maxillary bone on the cleft side
- Nasal floor is absent on cleft side (deficient maxillary bone)
- Medial premaxillary segment rotated externally and upward, internal and posterior rotation of the lateral minor maxillary segment on the cleft side

Cummings Chapter 188

Question 41

Discuss the anatomy of a bilateral cleft lip deformity. What are some of the other anatomical alterations associated with the unilateral cleft lip?

Answer 41

ANATOMY OF BILATERAL CLEFT LIP DEFORMITY:
- Orbicularis Muscle fibers run along the edge of the lateral aspect of the cleft
- Prolabial segment (middle part that is normally the philtrum) does not contain any useful muscle, typically filled with connective tissue
- Bilateral CL patients often have premaxillary and alveolar protrusion relative to the nasal septum
- Premaxillary bony deformity may push lip far anteriorly and superiorly toward the nasal tip, that columella is diminished in strength and height (may even be obliterated)
- Length of medial crura often inadequate
- Columella skin often insufficient
- Vermillion and white roll (skin edge of lip) is significantly deficient

ASSOCIATED ANATOMICAL ALTERATIONS WITH BILATERAL CLEFT LIP:
- Nasal deformity is typically symmetric/uniform
– Flared basal alar bases/laterally displaced
– Horizontally oriented nostrils
– Wide and flat nasal tip
– Short columella
– Short lower lateral cartilages
– Deficient skin overlying lower lateral cartilages

Cummings Chapter 188

Question 42

Describe the anatomic alternations that occur with a Cleft Palate - 5

Answer 42

1. Muscles of soft palate may be hypoplastic
2. Muscles are misdirected with abnormal insertions into the posterior hard palate
3. Mucosa that envelops muscle may be deficient (both oral and nasal sides)
4. Midline bony deficiency extending toward the incisive foramen may occur if hard palate cleft
5. Vomer usually unattached in isolated cleft palate, and may or may not be attached if cleft lip is present

Kevan peds Question 67

Question 43

What is the definition of a sequence?

Answer 43

Sequence = pattern of congenital anomalies that result from a single defect during development, with no known genetic cause

Question 44

Define Anomaly, Malformation, and Deformation

Answer 44

Anomaly = isolated non-syndromic abnormality (e.g. anomalous extra toe)

Malformation = intrinsic error in development of a tissue/organ/structure/function

Deformation = extrinsic pressure or force that alters the shape or position of an otherwise normal struture

Question 45

What is the difference between an association vs. syndrome?

Answer 45

Association = grouping of anomalies at higher frequency than statistically predicted, with no known cause

Syndrome = Association (of anomalies) with a single pathologic cause (e.g. genetic, chromosome, teratogenic, mechanical)

Question 46

XXWhat are the defining features of Pierre Robin Sequence?

Answer 46

1. Micrognathia (initiating event) - small body and short ramus
2. Glossoptosis
3. Airway Obstruction
4. Cleft palate (PRS not defined by cleft palate, but majority also have Cleft palate due to glossoptosis pushing back and palatal shelves fail to fuse, creating a U-shaped cleft)

Question 47

XXWhat are all the features that could be seen in Pierre Robin Syndrome?

Answer 47

1. Micrognathia
2. Glossoptosis
3. Cleft palate
4. Low external ear
5. Microtia
6. Ossicular abnormalities
7. CNVII anomalies
8. Inner ear hypoplasia

Vancouver 495

Question 48

XXWhat is the theory of the cause of non-syndromic pierre robin sequence?

Answer 48

• In utero, mandible gets stuck behind the sternoclavicular joint –> growth restriction of mandible.
• Mandible pops out @ 12-14 weeks and resumes growth, but can’t catch up

Question 49

XXWhat % of PRS is syndromic vs. anatomic (isolated)? How do their prognosis differ?

Answer 49

50-80% of PRS is Syndromic

Non-Syndromic PRS will likely resolve as kids grow & jaw catches up with rest of head (usually by 1 year old) - Therefore try to avoid major interventions!!!

Question 50

XXWhat is the key feature that differentiates a PRS cleft palate from an isolated cleft palate?

Answer 50

PRS cleft palate = U-shaped

Isolated cleft palate = V-shaped

Question 51

XXWhat are the syndromes associated with PRS?

Answer 51

“Small Mandible Will Cause A Vertical Tongue & Big Cleft”

S: Stickler (most common - 14-34%)
M: Moebius
W: Waardenburg
C: Crouzon
A: Apert
V: Velocardiofacial (or any 22q11)
T: Treacher-Collins
B: Beckwith-Wiedemann
C: CHARGE

Other:
- Fetal alcohol syndrome
- Diastrophic dysplasia (Decreased sulfate content, which affects cartilage & affects bone growth and height)
- Nager acrofacial dysostosis (Affects development of face, hands, and arms)
- Otopalatodigital Syndrome II (Primary bone dysplasia; encompasses a group of congenital anomalies that are characterized by skeletal dysplasia of varying clinical severity and an X linked dominant pattern of inheritance)
- Popliteal Pterygium
- Sphrintzen
- Deletion 6q
- Trisomy 11q, 18

Question 52

What are the syndromes associated with cleft palate?

Answer 52

1. Van der Woude syndrome (most common associated with Cleft lip and palate)
2. Microdeletions or additions of chromosome 22q11.2 (most common associated with isolated cleft palate)
3. DiGeorge Syndrome
4. Conotruncal anomaly face syndrome
5. Velocardiofacial syndrome
6. Popliteal pterygium syndrome
7. Extrodactyly ectodermal cleft syndrome
8. Down syndrome
9. All of those syndromes associated with PRS (e.g. Stickler)
10. Craniosynostoses (Apert, Crouzon, Pfeiffer)

Question 53

√Regarding Van Der Woude Syndrome, discuss:
1. Genetics & Inheritance
2. Clinical Features

Answer 53

INHERITANCE: Autosomal Dominant

Genetics: IRDF6

Features:
1. Vermillion pits (pits in the lower lip)
2. Missing teeth
3. Cleft lip and palate (most common genetic syndrome associated with cleft lip/palate)

Question 54

Discuss the management options for respiratory distress in Pierre Robin Sequence
List 6 conservative things
4 medical things
6 surgical things

Answer 54

OBSERVATION (No airway symptoms):
- Isolated non-syndromic mandible catch-up growth happens in first year, and can attain normal profile in 5-6 years
- If syndromic and micrognathia persists - observation not an option

CONSERVATIVE:
1. Prone/lateral positioning
2. Upright feeding
3. Haberman nipple (nipple for cleft palate to help provide suction)
4. Nasal trumpet (require frequent suctions and periodic replacement)
5. NG tube
6. OG tube

MEDICAL
1. PPI
2. Supplemental O2
3. Positive pressure O2 (NIPPV)
4. ETT

SURGICAL
1. Palatoplasty
2. Glossopexy (tongue-lip adhesion) - useful for occlusion secondary to anterior-posterior collapse, 56% dehiscence rate
3. Subperiosteal floor of mouth release
4. Mandibular distraction osteogenesis (primary treatment for obstruction solely because of glossoptosis) - Latency 1-5 days after placement, distract 1-2mm/day, consolidate after 4-8 weeks
5. Tracheostomy (for multiple reasons of airway obstruction)
6. Cleft palate repair

Vancouver 495
Nadia PRS Grand Rounds

Question 55

Describe the Medical considerations and management strategy for cleft lip and palate - 8

Answer 55

Multidisciplinary team approach!

1. Feeding difficulties
   - Haberman nipple
   - Monitor growth carefully
2. Hearing
   - Frequent COME
   - Monitoring hearing carefully
   - Consider early BMT
3. Associated anomalies
   - Look for other anomalies/syndromes
   - Genetic testing
   - Developmental delay possible
4. Airway
   - Midface growth restriction (25-35%)
   - Risk upper airway obstruction, especially if syndromic; monitor carefully
5. Psychosocial
6. Speech
7. Dental
8. Genetic counselling

Question 56

List the timing and timeline of interventions for the management of cleft lip and palate

Answer 56

10 weeks - 10 months - 10 years = lip-palate-alveolus

10 weeks: (3 months)
- Cleft lip repair (10 weeks, 10 lbs, 10hgb)

9-18 months:
- Cleft palate repair, consider concomitant BMT

3-5 years:
- VPI repair

5+ years:
- Lip revision (if needed)

6-9 years:
- Alveolar repair with bone grafting (just prior to canine development)

14-18 years:
- Orthognathic/dental surgery (After completion of maxillary growth)

16+ years:
- Rhinoplasty

Cummings protocol 188.2 figure Chapter 188

Kevan peds Question 75

Question 57

What are the features of cleft palate that predispose these kids to otitis media? What is the pathophysiology that leads to otitis media?

Answer 57

Eustachian tube in cleft child compared to non-cleft child:

1. Shorter
2. Larger angle between the cartilage and the tensor veli palatini
3. Cartilage is deformed with a greater cartilage cell density and less elastin at the hinge of the cartilage
4. TVP and LVP have less contractile tissue and more connective tissue
5. TVP and LVP have abnormal insertion into cartilage (lateral paratubal cartilage) and skull base
6. Relative position of the TVP causes baseline functional obstruction of the Eustachian tube

PATHOPHYSIOLOGY:
1. Unrepaired cleft causes obstruction at the nasopharyngeal end of the ET
2. Impaired ability to open the ET secondary to abnormalities described above
3. Induces negative middle ear pressure
4. Middle ear mucosal swelling
5. Middle ear fluid accumulation
6. Fluid stasis secondary to fluid accumulation and obstructed isthmus

70% of children with cleft palate obtain normal ET function 6-10 years after repair

Kids have increased risk of cholesteatoma

Timing of TT insertion is controversial

Question 58

What is the rate of tympanostomy tube placement in chlidren with cleft palate?
What are 3 common ear complications in patients with cleft palate?

Answer 58

1. 96% of children with CP required tympanostomy tube placement
2. 50% of those required repeat placement

Complications:
1. Chronic TM perforation 13%
2. Chronic suppurative otitis media 6%
3. Cholesteatoma 1-3%

Question 59

What adjuncts can be used prior to cleft palate surgery? What is the evidence behind these?

Answer 59

Presurgical Infant Orthopedics (PSIO)

Goals:
1. Realign the clefted maxillary shelves
2. Bring the widely separated lip margins together
3. Reshape the nose

Modalities:
1. Latham appliances (active technique - appliance screwed into palate)

2. Nasoalveolar molding (NAM)
   - Involves fabrication of a palatal appliance by orthodontist, shape changes over time to narrow width of the palatal cleft; followed by small cushions placed inside the nostril to provide traction - allows for better symmetry and repositioning of nasal tip and alar cartilages
   - For complete unilateral or bilateral clefts at ~1 week of age
   - Weekly evaluations + modifications until 3-4 months (immediately prior to definitive repair of the cleft lip/nose deformity)
3. Lip adhesion (passive)
   - Performed for patients not candidates for NAM
   - Wide complete clefts
   - Places soft tissue in more normal position to exert guiding forces along the major and minor maxillary segments
   - Performed at 1-2 months of age

Controversies:
- Studies fail to show long term benefit in dental arch, speech dvelopment, esthetics, function, and growth
- NAM: Additional cost, time, GA (For application), and treatment delay
- May increase risk of midfacial growth restrction (e.g. Latham device 100%)

NAM: https://www.childrenscolorado.org/globalassets/departments/surgery/cleft-lip-and-palate-clinic/fig2_tape-placement.jpg

Question 60

What are the five options for cleft lip repair?

Answer 60

Rule of 10s indications:
1. 10 weeks
2. 10 pounds
3. 10g of hemoglobin (usually 3months)

REPAIR OPTIONS:
1. Straight line closure (rarely used now)
2. MIllard rotation advancement technique
3. MIllard bilateral cleft repair
4. Tennison-Randall or Skoog techniques (single) triangular flap interdigitation
5. Double Triangular flap interdigitation

Question 61

Describe the techniques for cleft palate repair

Answer 61

Cleft palate repair goals:
1. Restoration of soft palate sling incorporating tensor and levator palate muscles (reconstruct the muscle sling of the LVP)

SOFT PALATE REPAIR ONLY:
- Schweckendiek (primary veloplasty), obturate hard palate until older
- Furlow double oppozing Z-plasty

SECONDARY CLEFT PALATE REPAIR:
- Von Langenbeck (bipedicled flap palatoplasty)

PRIMARY + SECONDARY CLEFT PALATE (just fixing secondary palate)
- Wardill-Kilner-Peet V-Y pushback technique
- Bardach uni-pedicle two flap palatoplasty

REPAIR OF COMPLETE CLEFT OF PRIMARY + SECONDARY PALATE, SECONDARY CP, OR SUBMUCOUS CLEFT:
- Furlow double opposing Z-plasty

Vancouver 501

Question 62

What are the complications of cleft lip and palate repair? 4

Answer 62

1. Perioperative adverse airway events: Can prevent issues by suturing tongue stitch around tongue tip and remove once the child is fully awake in PACU
2. Need for further surgery
3. VPI
4. Oronasal fistula

Question 63

What are the repair options for an oronasal fistula (following cleft palate repair)?

Answer 63

1. Obturator (difficult to tolerate)
2. Local rotation flap reconstruction (high failure rate)
3. Furlow opposing Z-plasty
4. Bilateral advancement flaps
5. Anteriorly-based dorsal tongue flap

Question 64

What test is typically performed to look for genetic anomalies?

Answer 64

FISH = Fluorescent in situ hybridization

Question 65

√Regarding CHARGE syndrome, discuss:
1. What are the genetics?
2. What are the clinical features?

Answer 65

GENETICS:
1. CHD7 gene mutation on chromosome 8q12 ( >60% cases)
2. Small amount have SEMA3E gene mutation
3. Autosomal dominant

Formerly an association, now a syndrome since gene has been found

FEATURES:
- C: Coloboma (conditions where normal tissue in or around the eye is missing at birth) - usually iris - 80%
- H: Heart defects (Tetrology of Fallot, patent ductus arteriosus, ventral septic defects, atrial septic defects, coarctation of the aorta, right-sided aortic arch)
- A: Atresia Choanal (Bilateral in 2/3 of cases, unilateral cases left side is more common)
- R: Retarded growth and/or development - CNS malformations (arrhinencephaly or holoprosencephaly)
- G: Genito-urinary problems - minor kidney anomalies, cryptorchidism, microphallus, congenital hypothyroidism, imperforate anus, pectus carinatum
- E: Ear abnormalities (outer/middle/inner/eight cranial nerve including CNHL SNHL and mixed) - Low set ears or posteriorly angulated, asymmetric, or cup-shaped pinna; Mondini dysplasia of the pars inferior and complete absence of the pars superior; HL often asymmetric

Ear anomalies %:
- Absent/hypoplasic SCCs >80%
- Absent/hypoplasic cochlea > 30%
- Oval window stenosis 71%
- Dysplastic stapes 50%

OTHER ANOMALIES:
- Robin sequence
- DiGeorge Sequence
- Facial asymmetry
- Micrognathia
- Feeding difficulties
- TEF
- Esophageal atresia
- Cleft lip or palate
- Upper airway abnormalities

OTHER ENT-RELATED FEATURES:
1. Airway - very large arytenoids, poor secretion management and aspiration, often require tracheostomy
2. TEF 20%
3. Cleft palate 20%
4. MR

Question 66

For the following syndromes, what types of eye colobomas do they have?
1. Goldenhar
2. Fraser syndrome
3. CHARGE
4. Tracher Collins

Answer 66

1. Goldenhar - upper lid
2. Fraser syndrome - upper lid
3. CHARGE - iris
4. Tracher Collins - outer third of the lower lid

Question 67

Define the following genetic terms:

1. Penetrance
2. Expressivity
3. Pleiotropy
4. Heterogeneity

Answer 67

Penetrance = Gene is present but not phenotypically detectable (e.g. “skipped generations”)

Expressivity = Variability in phenotypic appearance

Pleiotropy = Multiple phenotypic effects from single gene

Heterogeneity = Multiple genes/causes show similar phenotypic appearance/effects

Question 68

Define mosaicism with respect to genetics

Answer 68

Mosaicism = presence of both normal and mutated cell lines in same individual resulting from mutations in somatic cell line

(Different sets of cells)

vs. mutation is a cell passing on to a cell

Example: a person might possess some cells that have 46 chromosomes while other cells have 47 chromosomes. This difference in a person’s chromosomal makeup can contribute to health problems at birth, such as Mosaic Down syndrome, or cause issues later on in life.

Question 69

Define uniparental disomy (genetics).
Name 2 syndromes like this

Answer 69

Inheritance of both alleles from same parent (e.g. Prader-willi, angelman)

Question 70

Define mitochondrial inheritance (genetics)

Answer 70

Maternal transmission of mitochondrial DNA, all off spring are affected

Question 71

√What is craniosynostosis?

Answer 71

Birth defect in which the bones in a baby’s skull join together too early

Question 72

√Describe the approach to Craniosynostosis, based on history, physical exam, Investigations, and treatment

Answer 72

HISTORY:
1. Personal history
2. Family history
3. Genetics history
4. Head shape - observe from front, rear, sides, vertex

PHYSICAL EXAM:
1. Form and position of eyes and ears
2. Palpate sutures and fontanelles
3. Evaluate for signs of elevated ICP - sutural ridging, bulging fontanelles
4. Head circumference, AP, bifrontal, bitemporal, biparietal dematers
5. Vertical height of skull from supraorbital border
6. Dimensions of mandible and midface (cannot assess occlusion in neonate)
7. Symmetry
8. ROM of neck

INVESTIGATIONS:
1. CT
2. MRI

TREATMENT - Indications for surgery:
1. If mild, or presenting within first 3-6 months = Strip Craniectomy
2. Severe cases, especially if presents > 6 months = coronal/lambdoid osteotomies with out-fracture of parietal bones

Question 73

√Name 6 different skull deformities associated with a single suture synostosis

Answer 73

1. Synostotic trigonocephaly
2. Synostotic brachycephaly
3. Synostotic anterior plagiocephaly
4. Synostotic posterior plagiocephaly
5. Deformational posterior plagiocephaly
6. Synostotic scaphocephaly

Kevan Peds question 185

Question 74

√What is the common genetic mutation for all craniosynostoses?

Answer 74

FGFR2 mutations on chromosome 10

Autosomal dominant

Question 75

√List common craniosynostoses

Answer 75

1. Crouzon = Craniofacial Dysostosis Type 1
2. Apert = Acrocephalosyndactyly Type 1
3. Pfeiffer = Acrocephalosyndactyly Type 5

Vancouver 497

Question 76

√What is Crouzon syndrome? Discuss its features.

Answer 76

Crouzon = Craniofacial Dysostosis Type 1
- Premature fusion of bicoronal sutures

Inheritance = Autosomal Dominant
Genetics: FGFR-2 (fibroblast growth factor), chromosome 10q26

FEATURES:
1. Cone head (intracranial HTN –> optic nerve atrophy –> vision impairment)
2. Maxillary hypoplasia
3. Choanal atresia
4. Exorbitism (= shallow orbits and bulging eyes)
5. Hypertelorism
6. PRS
7. Normal IQ
8. Tracheal cartilaginous sleeve –> tracheal stenosis

“Crouzon Makes Croutons Edible However Pitiful Nut Taste”

Question 77

√Regarding Apert’s Syndrome, discuss:
1. Inheritance and Genetics
2. Clinical Features

Answer 77

APERT = Acrocephalosyndactyly Type 1
- Fusion of bones, including skull, hands, and feet bones

Inheritance = Autosomal Dominant
Genetics: FGFR-2 (fibroblast growth factor), chromosome 10q26

Like Crouzon but more pronounced severe features:
1. Cone head (intracranial HTN –> optic nerve atrophy –> vision impairment)
2. Maxillary hypoplasia
3. Choanal atresia
4. Exorbitism (= shallow orbits and bulging eyes)
5. Hypertelorism
6. PRS
7. Normal IQ
8. Tracheal cartilaginous sleeve –> tracheal stenosis

Additional features:
1. Syndactyly (fused or webbed fingers)
2. Stapes Fixation (CHL)
3. Mental retardation

Question 78

√What is Pfeiffer syndrome? Discuss the different types, and features of each.

Answer 78

PFEIFFER = Acrocephalosyndactyly Type 5

Inheritance = Autosomal Dominant
Genetics: FGFR-2 (fibroblast growth factor), chromosome 10q26

Features = Crouzon’s plus:
1. Clover-leaf head (all sutures prematurely fused)
2. Wide/fused digits
3. Mental retardation

Crouzon’s features:
1. Cone head (intracranial HTN –> optic nerve atrophy –> vision impairment)
2. Maxillary hypoplasia
3. Choanal atresia
4. Exorbitism (= shallow orbits and bulging eyes)
5. Hypertelorism
6. PRS
7. Normal IQ
8. Tracheal cartilaginous sleeve –> tracheal stenosis

THREE TYPES OF PFEIFFER:
1. Type 1: Mild, fairly asymptomatic
2. Type 2 & 3: Severe deformity, increased ICP, early death

Question 79

√What are 3 conditions with congenitally shallow orbits?

Answer 79

1. Crouzon
2. Apert
3. Pfeiffer

Question 80

√What are the indications for surgical intervention in craniosynostosis? 2

Answer 80

1. Clinically significant increased ICP
   - See below
2. Psychosocial impact on child/family
   - On child: self esteem, suicidality, behaviour, friendships, school performance, frontal inhibition, lower IQ, etc.
   - On family: stress, marital conflict, family strife, high divorce rates

EVIDENCE OF SIGNIFICANT INCREASED ICP
1. History
- ++ irritable, especially when lying down
- ++ vomiting/projectile vomiting, waking from sleep to vomit
- Decreased LOC
- Decreased tone

2. Physical Exam
   - Papilledema (difficult to diagnosed in infants)
   - Hypotonic
   - Hyperreflexia
3. Diagnosis
   - CT Head: bony compression, enlarged ventricles
   - MR Venogram: Venous congestion
   - Definitive: Ventricular manometry probe (like VP shunt)

Note in children:
1. We don’t know what normal ICP level should be
2. How much ICP is too much in a baby with open sutures?
3. High ICP doesn’t always correlate with decreased IQ or development
4. Normal investigations don’t rule out increased ICP

Question 81

√What are surgical options for cranial reconstruction for craniosynostosis?

Answer 81

1. Osteotomies + bone grafting, plating in new position
   - Leave big bony gaps, wait for them to fill in over time
   - Higher risk CSF leak, meningitis
2. Distraction Osteogenesis
   - Insert screws: parents distract 1mm/day, new osteoid continually grows to fill small but ever-expanding gap
   - Preferred method

Question 82

√Regarding Achondroplasia, discuss:
1. Inheritance and Genetics
2. Clinical features
3. Associated syndromes

Answer 82

INHERITANCE:
- Autosomal dominant most common

GENETICS:
- Mutations of FGFR-3 gene (fibroblast growth factor). chromosome 4p16.3

FEATURES:
- Most common cause of short limb dwarfism
- Short limbs
- Genu varum (legs curve outward when feet/ankles touch)
- Limited elbow extension
- Trident hand
- Long trunk
- Lumbar lordosis
- Frontal bossing
- Sunken nasal bridge
- Midface hypoplasia
- CHL in 60%
- NORMAL COGNITION/IQ!!

ASSOCIATED SYNDROMES: “BAGMV”
1. Beckwith-Wiedemann
2. Goldenhaar
3. Mobius
4. VACTERL

Question 83

What is the general approach to treatment of children with cranial/facial defects (including clefts)? What is the main ENT role(s)

Answer 83

Multidisciplinary team approach:
- SLP
- Audio
- OT
- Dietary
- PT
- Genetics
- Peds
- Respirology
- Plastics
- OMFS
- NSx
- CV surgery

ENT Primary roles:
1) Airway
2) Ears

0-3 months: Establish/ensure adequate airway, feeding
3-6 months: Hearing/auditory rehab
~12 months: Cranial vault, cleft lip/palate repairs
~5-10 years: Bony recon/distraction (e.g. orbits, zygoma, maxilla, TMJ, alveolus)
14-20 years: Orthognathic surgery, orthodontics, cosmetic surgery

Question 84

XXRegarding Stickler Syndrome, discuss:
1. What is an alternative name
2. What are the genetics and inheritance patterns?
3. What are the features?

Answer 84

Stickler Syndrome = Hereditary Progressive Arthro-Ophthalmopathy

GENETICS:
1. Chromosome 12
2. COL2A1, COL9A1, COL11A1, COL11A2 – encodes Type II, IX, XI collagen
3. Autosomal dominant - variable expressivity

FEATURES:
1. Midface underdevelopment
2. Mandibular hypoplasia
3. Cleft palate
4. 30-40% pierre robin sequence (micrognathia, glossoptosis, cleft palate, airway obstruction) also have stickler syndrome
5. SNHL (moderate to severe) or mixed HL (80%)
6. Progressive myopia
7. Retinal detachment
8. Cataracts
9. Skeletal and joint anomalies - hypermobile, enlarged joints, early arthritis
10. ETD and CHD (secondary to cleft palate)

What does CHD stand for?

Kevan Peds Question 186

Question 85

XXRegarding Treacher-Collins syndrome, discuss:
1. What is an alternative name
2. What are the genetics and inheritance patterns?
3. What are the features?

Answer 85

= Mandibulofacial dysostosis
- Malformation of the 1st and 2nd branchial arch

GENETICS:
- TCOF gene on chromosome 5q –> encodes TREACLE protein
- Autosomal dominant, with variable penetrance and expressivity; 60% sporadic

FEATURES:
1. Zygomatic hypoplasia, non-fusion of arches
2. Midface hypoplasia, flat naso-frontal angle
3. Narrow nares, hypoplastic alar cartilages
4. Choanal atresia
4. Micrognathia
5. Down slanting palpebral fissues (“Antimongoloid”)
6. Hypoplasia supraorbital rims
6. Lower lid coloboma (vs. upper lid in Goldenhaar syndrome)
7. Deficient eyelashes in the medial two thirds of the lower eyelids
8. Ear anomalies: outer (dysplastic, microtia, EAC stenosis or atresia, preauricular tags and fistulas), middle (ossicular fixation or malformation) - CHL 30%, inner - mondini malformation (SNHL, more rare)
9. Mandibulofacial dysostosis associated with PRS and palatal clefting in 35% of cases
10. Severe OSA secondary to micrognathia and glossoptosis –> may require tracheostomy
11. Dental abnormalities
12. NORMAL IQ!!

Question 86

√What is Nager Syndrome?

Answer 86

= 1st and 2nd branchial arch malformations

Features: Treacher collins, plus:
1. Limb defects
2. Severe cleft palate

Treacher Collins syndrome features:
1. Zygomatic hypoplasia
2. Midface hypoplasia
3. Choanal atresia
4. Micrognathia
5. Down slanting palpebral fissues
6. Lower lid coloboma
7. Deficient eyelashes in the medial two thirds of the lower eyelids
8. Ear anomalies: outer (dysplastic), middle (ossicular fixation), inner (CHL; SNHL is rare)
9. Mandibulofacial dysostosis associated with PRS and palatal clefting in 35% of cases
10. Severe OSA secondary to micrognathia and glossoptosis –> may require tracheostomy
11. Normal IQ

Question 87

√Regarding branchio-oto-renal syndrome (BOR), discuss:
1. What is an alternative name
2. What are the genetics and inheritance patterns?
3. What is the diagnostic criteria?

Answer 87

= Melnick-Fraser Syndrome

GENETICS:
1. EYA1 gene on chromosome 8q
2. Autosomal dominant (variable penetrance and expressivity)

DIAGNOSIS: 3 Major criteria; OR 2 major + 2 minor criteria

Major criteria (5):
1. 63% Branchial cysts / cleft anomalies
2. Pinna malformations (41%)
3. Pre-auricular pits (77%)
4. Hearing loss (89%); mondini malformation (ossicular & cochlear malformations)
5. 66% Renal anomalies (mild to complete agenesis, polycystic kidneys, duplicated ureters) - (get a renal US or IV pyelogram)

Minor criteria (3):
1. Pre-auricular tags
2. Lacrimal duct aplasia
3. Short palate

Kevan Peds Question 189

Question 88

√Regarding Waardenburg Syndrome, discuss:
1. What are the genetics and inheritance patterns?
2. What part of the inner ear does Waardenburg affect?
3. What are the types and clinical features?

Answer 88

GENETICS:
- Multiple (e.g. PAX3 chromosome 2)
- Autosomal dominant

TYPES (and genetics):
1. WS1 = PAX3, chromosome 2q37
2. WS2 = MITF on 3p12-14 (Microphthalmia transcription factor), SNAI2, SOX10
3. WS3 (Klein-Waardenburg Syndrome) = PAX3 on 2q37
4. WS4 (autosomal recessive) = EDNRB
- Shah-Waardenburg or Waardenburg syndrome-Hirschsprung disease = EDN3, SOX10

HEARING LOSS:
- Affects the stria vascularis of the inner ear (causes developmental defects of cochlear melanocytes, located as intermediate cells in the stria vascularis)

FEATURES:
1. WS1
- SNHL 20% (unilateral or bilateral) ± Vestibular symptoms
- White forelock, premature graying
- Pigment abnormalities of skin - vitiligo
- Pigmentary disturbances of the iris
- Dystopia canthorum (increased distance between inner corners of the eyelids/medial canthi)
- Displacement of the inner canthi and lacrimal puncta
- Synophrys (fusion of eyebrows / unibrow)
- Broad nasal root
- Hypoplasia of the alae nasi
- Patent metopic suture
- Square jaw

2. WS2
   - WS1 except no dystopia canthorum
   - SNHL 50%
3. WS3
   - WS1 features plus:
   - hypoplasia or contracture of the upper limbs (skeletal dysplasia)
   - blue eyes
   - Muscular hypotonia
   - Unilateral ptosis
4. WS4
   - Autosomal recessive
   - Hirschsprung disease / megacolon

Other features:
- Heterochromia/pale eyes
- White forelock (poliosis), premature greying
- Unibrow (synophys)
- Pigmentary changes
- Hypertelorism (dystopia canthorum)
- SNHL - Mondini malformation, Scheibe’s aplasia both associated

Kevan peds Question 189##

Metopic suture: https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcTTVkPq1-UzKzNIhDNQakmz9JErLXgSmHw3fjU83fSsbw&s

Question 89

XXRegarding Goldenhar Syndrome, discuss:
1. What is an alternative name
2. What are the causes?
3. What are the features?
4. What is the descriptive classification?

Answer 89

DEFINITION:
- Hemifacial microsomia
- Oculo-auriculo-vertebral dysplasia
- 1st and 2nd branchial arch syndrome

CAUSE:
- Most cases sporadic, some autosomal dominant
- No specific molecular etiology has been identified
- Hypothesis: unilateral hemorrhagic event involving the stapedial artery during early craniofacial development

FEATURES:
- Unilateral facial asymmetry/hemifacial microsomia (90%) - can be bilateral, but then asymmetric
- Maxillary/zygomatic/mandibular hypoplasia and asymmetry
- Hypoplastic facial musculature
- Facial paresis or paralysis varying degrees
- Cleft lip and palate
- External and middle ear deformities (atresia of the EAC, preauricular skin tags, ossicular abnormalities, CHL > SNHL)
- Ocular involvement (upper lid colobomas (vs. Treacher collins lower lid), epibulbar choristomas/dermoids, blepharophimosis, strabismus)
- Fusion of vertebrae (esp. cervical)
- Spina bifida

Kevan Peds Question 190
Vancouver 498

Question 90

Describe the OMENS classification of facial defects

Answer 90

O: Orbital asymmetry
M: Mandibular hypoplasia
E: Ear anomalies
N: Nerve involvement
S: Soft tissue deficiency

OMENS-plus: expanded spectrum to include:
- Cardiac, skeletal, pulmonary, renal, GI, and limb anomalies

ORBIT
- 0: Normal size and position
- 1: Abnormal orbital size
- 2: Abnormal orbital position
- 3: Abnormal orbital size and position

MANDIBLE (as per Pruzansky Classification)
- 0: Normal
- 1: Small mandible and glenoid fossa with short ramus
- 2: Ramus short and abnormally shaped
- 2A: Glenoid fossa in anatomically acceptable position
- 2B: TMJ inferiorly, medially, and anteriorly displaced, with severely hypoplastic condyle
- 3: Complete absence of ramus, glenoid fossa, and TMJ

EAR (as per Jahrsdoerfer Classification)
- 0: Normal
- 1: Minor hypoplasia and cupping with all structures present
- 2: Absence of external auditory canal with variable hypoplasia of concha
- 3: Malpositioned lobule with absent auricle, lobular remnant usually inferiorly anteriorly displaced

NERVE (Facial Nerve)
- 0: No FN involvement (normal function)
- 1: Upper facial nerve involvement (temporal and zygomatic branches)
- 2: Lower facial nerve involvement (buccal, mandibular, or cervical)
- All branches affected

SOFT TISSUE:
- 0: No obvious tissue or muscle deficiency
- 1: Minimal soft tissue or muscle deficiency
- 2: Moderate soft tissue or muscle deficiency
- 3: Severe soft tissue or muscle deficiency

Question 91

√Regarding Neurofibromatosis 1, discuss:
1. Alternative names
2. Genetics and inheritance
3. Clinical features
4. Diagnostic features

Answer 91

NF 1
= Neurofibromatosis 1
= Von Recklinghausen Disease

GENETICS:
1. Autosomal dominant
2. NF1 gene (Neurofibromin (aka NF1-related) protein) on chromosome 17q11.2 - “nerve growth factor Neurofibromin”
3. Caused by deletions, insertions, translocations, and point mutations

CLINICAL FEATURES:
- Blindness
- SNHL
- Vestibular schwannomas in 5%

DIAGNOSTIC FEATURES (Requires minimum 2 of the 7 criteria following):
1. > 6 cafe-au-lait macules (> 0.5cm in children, or >1.5cm in adults)
2. ≥ 2 cutaneous/subcutaneous neurofibromas; OR one plexiform neurofibroma
3. Axillary or groin freckling > 2
4. Optic pathway glioma
5. ≥ 2 Lisch nodules (iris hamartomas seen on slit lamp examination)
6. Bony dysplasia (sphenoid wing dysplasia, bowing of long bone ± pseudoarthrosis (bone nonunion), scoliosis, thinning of tibia)
7. First degree relative with NF1

Question 92

√Regarding NF2, discuss:
1. Genetics and inheritance
2. Clinical Features
3. What is included in the diagnostic workup?
4. What are the subtypes?
5. Diagnostic criteria
6. What is the concern for treating VS related to NF2 with radiation?

Answer 92

GENETICS:
1. Autosomal dominant with 95% penetrance
2. 22q11-q13 (NF2 gene) –> encodes Merlin or Schwannomin protein (Merlin iis a tumor suppressor protein)
3. 50% casees due to SPONTANEOUS mutations

CLINICAL FEATURES:
- 95% incidence of bilateral vestibular schwannomas, often before age 21
- Central meningiomas, gliomas, schwannomas, early lens opacifications (cataracts)
- Fewer cafe au lait spots and cutaneous nodules than NF1

WORKUP INCLUDES:
1. Ophthalmology evaluation (r/o cataracts)
2. Genetic screen
3. Whole body scan/spine
4. Psychosocial support
5. Family planning

SUBTYPES OF NF2:
1. Wishart: Early onset, rapid growth, other tumors than vestibular schwannomas
2. Gardner: Slower rate of growth & slower onset, usually only bilateral vestibular schwannomas

RISK:
- Malignant transformation following stereotactic radiation

DIAGNOSTIC CRITERIA:

Bailey’s:
1. Bilateral vestibular schwannoma seen with appropriate imaging technique (CT or MRI); or
2. A first degree relative with NF2 and either unilateral 8th nerve mass;
Or two of the following:
- Neurofibroma
- Meningioma
- Glioma
- Schwannoma
- Juvenile posterior subcapsular lenticular opacity

Cumming’s:
1. Bilateral vestibular schwannoma that usually develops by second decade of life; Or
2. Family history of NF2 in a first-degree relative, plus ONE of the following:
- Unilateral vestibular schwannoma before age 30; or
- Any two of: meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacities/juvenile cortical cataract

STAT PEARLS:
A. ONE of the following:
1. Bilateral VS
2. Identical NF2 pathogenic variant in two or more anatomically distinct NF2-related tumors (schwannoma, meningioma, and/or ependymoma)
3. Two major criteria
4. One major and two minor criteria

Major criteria:
1. Unilateral vestibular schwannoma
2. First degree relative other than a sibling with NF2
3. Two or more meningiomas
4. NF2 pathogenic variant in an unaffected tissue (e.g. blood)

Minor criteria:
1. Ependymoma, schwannoma (non-vestibular)
2. A single meningioma
3. Juvenile subcapsular or cortical cataract, retinal hamartoma, epiretinal membrane in a person age < 40 years

Question 93

√Regarding Moebius / Mobius Syndrome, discuss:
1. Cause
2. Features

Answer 93

CAUSE:
- Unknown - hypoxemic/ischemic injury during development
- Sporadic

FEATURES:
1. Cranial Nerve Hypoplasias
- VII (100%) - bilateral, complete facial paralysis
- VI (75%) - lateral gaze palsy (cross-eyed)
- XII (25%) - speech swallowing difficulty
- IX, X - bilateral VFP
- All other CN possible (VIII usually spared)
2. PRS
3. Kallman syndrome - anosmia, delay/prevent puberty
4. Hand/foot anomalies
5. External ear deformities
6. Mixed hearing loss
7. Normal IQ, but 30% autistic

Question 94

√What is Poland Mobius Syndrome?

Answer 94

Congenital absence of Pectoralis muscle

Question 95

XxRegarding Melkersson-Rosenthal Syndrome, discuss:
1. Other names
2. Cause
3. Associations
4. Features
5. Treatment

Answer 95

= Chelitis Granulomatosa

CAUSE:
- Most cases sporadic
- Familial occurrences suggest autosomal dominant
- Local immune response and vasomotor disturbance affecting the vasa vasorum (small blood vessels that supply the walls of larger arteries/veins) of the vessels supplying the facial nerve

ASSOCIATIONS:
1. Orofacial granulomatosis manifestations, including (noncaseating granulomas):
- Sarcoidosis
- Crohn’s disease
- Melkersson-Rosenthal syndrome
- TB
- Foreign Body reaction

FEATURES:
1. Recurrent facial paralysis (usually unilateral, partial)
2. Recurrent facial edema (especially upper lips)
3. Fissured tongue
4. Defects in taste –> anterior 2/3s
5. Exposure keratitis (damage to cornea from dryness due to incomplete eye closure)

TREATMENT:
1. Surgical excision and reconstruction recommended for swollen orofacial tissues
2. Total facial nerve decompression for recurrent facial palsy
3. NSAIDs, steroids, immunosuppressives, antivirals

Question 96

√Regarding Charcot-Marie-Tooth Syndrome, discuss:
1. Genetics and Inheritance
2. Features

Answer 96

GENETICS:
1. Autosomal dominance
2. PMP22 duplication on chromosome 17

FEATURES:
1. Progressive peripheral neuropathy: dysphagia, dysphonia, foot drop “pez cavus”
2. Risk factor for auditory neuropathy

Question 97

Regarding McCune-Albright Syndrome, discuss:
1. Genetics and Inheritance
2. Features

Answer 97

GENETICS:
1. RANDOM mutation of GNAS on chromosome 20 (NOT inherited)

FEATURES: 3 P’s
1. Polyostotic fibrous dysplasia (disseminated fibrous dysplasia Type 3 - younger patients)
- 75% involve long bones
- 50% involves facial bones
2. Pigmentation (Cafe au Lait spots)
3. Precocious pubery
- PLUS other hyper endocrinopathies: DM, Thyroid goiter, hyperthyroidism, cushing, testicular abnormalities, acromegaly

Question 98

Regarding Osteogenesis Imperfecta, discuss:
1. Alternative names
2. Genetics/Inheritance
3. Types
4. Features - 6

Answer 98

= Van Der Hoeve Syndrome

GENETICS:
1. Autosomal dominant (except for one type of Progressive)
2. Gene COL1A1 and COL1A2 on Chromosome 17
3. Type 1 collagen defect (most abundant collagen type in body)

TYPES OF OSTEOGENESIS IMPERFECTA:
1. MILD: Insufficient quantity, normal quality
- Embryotoxon (circular anomalies in peripheral of the cornea), keratoconus (protruding cornea), megalocornea (big)
2. SEVERE/LETHAL: Poor quantity, poor quality
3. PROGRESSIVE AUTOSOMAL RECESSIVE: Normal quantity, defective collagen
- Blue sclera fades after first year of life
4. PROGRESSIVE: Normal quantity, poor quality
- Normal sclera

FEATURES:
1. Deformed, brittle bones (sparse trabeculae and thin cortex)
2. Dental anomalies
3. Joint elasticity
4. Blue sclera (secondary to increase in non-collagenous matrix and molecular disorganization)
5. Restrictive thoracic cage –> respiratory problems
6. Conductive hearing loss and SNHL - 50%
- IAC grossly widened
- Stapes is the most affected ossicle

Question 99

What is the association between scleral color and hearing loss in osteogenesis imperfecta?

Answer 99

• Patients with osteogenesis imperfecta can develop CHL, SNHL, or mixed loss
• Blue sclera patients are more likely to develop CHL (From stapes fixation)
• Gray/white sclera are more likely to develop SNHL

Question 100

√Regarding Pendred Syndrome, discuss:
1. Genetics and inheritance
2. Features
3. Diagnosis and treatment?

Answer 100

GENETICS:
1. Autosomal recessive
2. SLC26A4 gene, pendrin protein on chromosome 7q31 (“7 letters in pendred)
3. Most common syndrome associated with SNHL (10% of patients with syndromic hearing loss)

FEATURES:
1. Congenital, progressive bilateral SNHL
2. Enlarged vestibular aqueduct (most common abnormality)
3. Mondini malformation
4. Hypoplastic cochlea, large semicircular canals
5. Euthyroid goiter (75%) - tyrosine iodination defect

DIAGNOSIS:
1. Perchlorate discharge test (tests how well the thyroid gland takes up iodine)

TREATMENT:
1. Exogenous T4

Question 101

√Regarding Usher Syndrome, discuss:
1. What is Usher syndrome well known for?
2. Genetics
3. Types
4. Investigations and treatment
5. Features

Answer 101

1. MOST COMMON cause of congenital deaf-blindness
2. Most common cause of Autosomal recessive syndromic hearing loss

GENETICS:
1. Multiple, e.g. MYO7A (Type1), USH2A (Type2)
2. Types 1-4 (most autosomal recessive ecept type 4 = x-linked recessive inheritance in rare instances)

TYPES:
1. US type 1 (US1) - MOST COMMON 90% - characteristics include:
- Profound SNHL from birth
- Do not usually benefit from hearing aids
- Severe balance problems (no vestibular response)
- Vision problems/retinitis pigmentosa begin by age 10
- Blindness eventually occurs
2. US type 2 (US2) - 2nd MOST COMMON 10% - characteristics include:
- Moderate to severe SNHL
- Usually benefit from hearing aids
- Use speech to communicate
- Normal or decreased vestibular response/balance
- Retinitis pigmentosa begins in teenage years
3. US type 3 (US3) - < 1% cases - characteristics include:
- Progressive HL (Born with normal hearing, hearing problems develop in teenage years, deafness by late adulthood)
- Near normal balance
- Retinitis pigmentosa begins around puberty
- Blindness by mid-adulthood

INVESTIGATIONS:
1. Ophthalmology consult esseential
2. Electroretinography (measures potentials of retinas from light and visual stimuli)

TREATMENT: Amplification of hearing

FEATURES:
1. Retinitis pigmentosa (progressive bisual loss) - eye changes detected on electroretinography even before fundoscopic changes
2. Atrophy of organ of corti –> SNHL
3. Schiebe’s aplasia
4. Ataxia/vestibulopathy common

(Kevan Peds Q199)

Question 102

√Regarding Jervell-Lange-Nielsen Syndrome, discuss:
1. Genetics
2. Features
3. Work-up needed if suspicious of diagnosis
4. Treatment

Answer 102

GENETICS:
1. Autosomal recessive
2. KCNE1 and KCNQ1 gene mutation on chromosome 11p15 (potassium channel functions in heart and cochlea)

FEATURES:
1. Bilateral sensorineural hearing loss, worse in high frequency; Scheibe’s aplasia associated occasionally
2. Prolonged QTc interval –> Tosades and sudden cardiac death
3. Large T-waves
4. Recurrent syncope
5. Stokes-Adams attacks (drop attacks)
6. Sudden death

INVESTIGATIONS:
1. ECG: Prolonged QTc, large T waves
2. Audiometry

TREATMENT:
1. Beta-blockade
2. Amplification

Question 103

Regarding Kallmann Syndrome, discuss:
1. Genetics
2. Features - 2
3. Workup
4. Treatment

Answer 103

GENETICS:
1. KAL1, ANOS1, FGFR1 mutations - defect in GnRH neurons of hypothalamus
2. X-linked most common, but also AR and AD types

FEATURES:
1. Hypogonadotropic hypogonadism –> incomplete puberty
2. Anosmia (agenesis of olfactory bulb)

WORK-UP:
1. UPSIT test
2. MRI (absent olfactory bulb)
3. Labs: FSH, LN, Prolactin, GnRH
4. Genetics

Treatment:
1. Referral to Endo and Genetics

Kevan Q200 and Statpearls

Question 104

√Regarding Mucopolysaccharidosis, discuss the 3 main types, their causes and features for each.

Answer 104

Mucopolysaccharidoses are a group of inherited metabolic diseases caused by the absence or malfunctioning of certain enzymes the body needs to break down molecules called glycosaminoglycans.
- Lysosome storage disorders

MUCOPOLYSACCHARIDOSIS TYPE 1 = HURLER SYNDROME

Cause:
1. a-1-iduronidase enzyme deficiency –> leads to buildup of glycosaminoglycans in end organs (accumulation of heparan, dermatan, keratan-sulfates in lysosomes)
2. IDUA gene, chromosome 4
3. Autosomal recessive

Features:
1. Organomegaly, macrocephaly
2. Enlarged tongue (macroglossia)
3. Hearing loss
4. Airway obstruction, OSA
5. Mental retardation, progressive neurologic dysfunction
6. Cloudy corneas (distinguishes from Hunter’s)
7. Broad face, low nasal bridge
8. Rapid progressive decline –> death by 10 years old (first decade)

MUCOPOLYSACCHARIDOSIS TYPE 2 = HUNTER SYNDROME

Cause:
1. Iduronate-2-sulfatase enzyme deficiency (lysosome storage disease) –> leads to build up of glycosaminoglycans in end organs (heparan sulfate, dermatan sulfate)
2. X-linked recessive

Features:
1. Similar to Hurler, but slower decline, less severe –> death by 16-65 years
2. No cloudy corneas
3. Death usually occurs from infiltrative cardiomyopathy and valvular disease leading to CHF

MUCOPOLYSACCHARIDOSIS TYPE 3 = FABRY DISEASE

Cause:
1. a-galactosidase A deficiency –> leads to buildup of sphingolipids in end organs
2. X-linked

Features:
1. Peripheral neuropathy (CNS, PNS)
2. Vasculitis (CVS, GU, GI)
3. Dermatitis
4. Cloudy corneas
5. Ears: tinnitus, vertigo, SNHL

Vancouver 509

Question 105

√What are the anesthetic risk factors in a child with Mucopolysaccharidosis?

Answer 105

Hypopharynx:
- Narrow due to redundant tissue
- Large tonsils and adenoids

Neck:
- Cervical cord compression
- Atlanto-axial instability

Oral cavity:
- Macroglossia
- Limited mouth opening

Cardiac:
- Coronary disease
- Valve disease
- Heart failure
- Significant arrhythmias
- Pulmonary HTN

Respiratory:
- Restrictive lung disease
- Obstructive lung disease
- Breathing at closing capacity
- Narrow trachea

Question 106

Regarding Gorlin syndrome, discuss:
1. Other names
2. Genetics and inheritance
3. Features

Answer 106

= Nevoid Basal Cell Carcinoma Syndrome

GENETICS:
1. PTCH1 gene on chromosome 9 - tumor suppressor gene
2. Autosomal dominant

Features: “ABBBBCCC”
1. Acral pitting
2. BCCs (many, early)
3. Frontal Bossing
3. Bifid ribs
4. MedulloBlastomas (brain tumor)
5. Odontogenic keratoCysts (75%) - “wavy parakeratosis, cystic space, and picket fence pallisading”
6. Calcified falx cerebri
7. Cataracts

Question 107

Regarding Xeroderma Pigmentosum, discuss:
1. Genetics and causes
2. Features - 4

Answer 107

XP is a failure of DNA repair damaged by UV light

GENETICS:
1. Autosomal recessive
2. Multiple genes: XPA/B/C/D
3. 6x more common in Japanese

FEATUERS:
1. Severe sunburns
2. +++ Freckling with minimal sun exposure
3. High risk BCC, SCC, melanoma
4. Early death (20 years) secondary to metastatic melanoma/SCC

Question 108

√Regarding Von Hippel Lindau Syndrome, discuss:
1. Genetics
2. Features

Answer 108

GENETICS:
- Mutation of VHL gene (tumor suppressor) in chromosome 3
- Autosomal dominant

FEATURES:
1. Endolymphatic sac tumors (11%)
2. Paragangliomas (especially pheochromocytoma)
- Retinal/CNS hemangioblastoma
- Renal cell cancer
- Pancreatic tumors (cystadenomas, neuroendocrine tumors)
- Pheochromocytoma
- Epididymal cystadenomas

Mnemonic “HiPPEL”
H: Hemangioblastoma (Cerebellum, spine, retina)
i: i-Renal (clear cell RCC)
P: Pancreatic tumors (cystadenomas, neuroendocrine tumors)
P: Pheochromocytoma
E: Epididymal cystadenomas
L: endoLymphatic sac tumors

Question 109

XXList craniofacial (and ENT significant) features of Down Syndrome

Answer 109

Eyes:
1. Upslanting palpebral fissures
2. Epicanthal folds
3. Brushfield spots (iris white spots)

Nose:
1. Broad, flat nasal root
2. Small nose
3. Narrow nasopharynx

Cheek:
1. Malar hypoplasia
2. Midface hypoplasia

Ears / Temporal bone:
1. Small, low-set ears
2. Small, narrow, tortuous EACs
3. Eustachian tube dysfunction
4. Enlarged vestibular aqueduct
5. Semicircular canal dysplasia

Oral:
1. Small mouth
2. Dental abnormalities:
3. Large fissured lips
4. Relative macroglossia, fissured

Airway:
1. Small larynx
2. SGS common (elliptical cricoid)
3. Complete tracheal rings

Head/Neck:
1. Flat occiput
2. Brachycephaly
3. Atlanto-axial instability and subluxation
4. Short neck
5. Microgenia

Other:
1. Hypotonia
2. Obesity
3. Mental retardation

Question 110

√What are the anesthetic concerns for patients with Down Syndrome?

Answer 110

1. Spine instability
2. Large tongue
3. Subglottic stenosis
4. Small larynx
5. Hypotonia (pharyngeal muscles collapse easily)

Question 111

√What are 8 reasons why Down Syndrome is susceptible to OSA?

Answer 111

1. Hypoplastic midface and cranium
2. Narrow nasopharynx
3. Macroglossia
4. Muscular hypotonia
5. Obesity
6. Increased susceptibility to upper respiratory tract infections
7. Small larynx
8. Subglottic stenosis

UPPP may be useful in this population

Question 112

√Regarding Beckwith-Wiedemann Syndrome, discuss:
1. Genetics, protein, inheritance
2. Features

Answer 112

Inheritance: Sporadic
Protein: Thyroid transcription factor 2 (TTF-2)
Genes:
1. Complex - usually involves many genes of Chromosome 11

FEATURES:
1. Macroglossia –> airway risk, chronic alveolar hypoventilation
2. External ear creases
3. Pinna pits
4. Omphalocele (birth defect in abdominal wall)
5. Gigantism, organomegaly/visceromegaly
6. Hypoglycemia
7. Cytomegaly of adrenal cortex
8. PRS

Question 113

List 6 syndromes associated with macroglossia

Answer 113

1. Beckwith Wiedemann
2. Opitz-Frias
3. Hunters
4. Hurlers
5. Down Syndrome (relative)
6. Melkersson-Rosenthal (relative)

Question 114

List 6 non-syndromic causes of macroglossia

Answer 114

1. Amyloidosis
2. Allergy/anaphylaxis
3. Hemangioma
4. Lymphatic malformation
5. Hypothyroidism
6. Lingual thyroid

Question 115

What are the diagnostic features of macroglossia? 5

Answer 115

1. Tongue protrudes beyond teeth
2. Dental impressions seen on tongue
3. Mandibular prognathism
4. Open bite deformity
5. Malocclusion

Question 116

What are 3 causes of pseudomacroglossia?

Answer 116

1. Micro/retrognathia
2. Tongue posturing
3. Hypotonia

Question 117

What are 6 surgical options for macroglossia?

Answer 117

1. Anterior wedge
2. Tip amputation
3. Midline glossectomy
4. Horizontal filleting
5. Keyhole
6. Combination

Keyhole: https://www.researchgate.net/profile/Orlando-Tanaka/publication/289673947/figure/fig6/AS:316123112329220@1452381031419/Glossectomy-a-keyhole-shaped-technique-was-used-to-decrease-the-width-and-length-of-the.png

Question 118

√Regarding Alport Syndrome, discuss:
1. Genetics and Inheritance
2. Features
3. Types
4. Investigations
5. Treatment

Answer 118

GENETICS:
1. COL4A3/4/5 - codes for Type IV collagen
2. 85% X-linked dominant (COL4A5 gene)
3. 15% Autosomal recessive (COL4A3 and COL4A4 gene)
4. Small portion is autosomal dominant - also COL4A3/4 - unsure why some inherit this dominant vs. recessive

General Features:
- Hearing loss
- Varying degrees of renal disease
- Death in males by age 30 (due to renal failure)

FEATURES (Must have at least 4 or more):
1. Family history of nephritis/hematuria
2. Hematuria NYD (present in 100%)
3. Glomerular base membrane (GBM) abnormalities
4. Personal or family history of ESRD
5. Progressive bilateral SNHL (usually 2nd decade) - degeneration of organ of corti & stria vascularis
6. Ocular lesions (anterior lenticonus - abnormal cone protrusion)
7. Esophageal leiomyomas (fibroids - benign smooth muscle tumor)
8. Positive gene mutation

INVESTIGATIONS:
1. BUN
2. Creatinine
3. Urinalysis

TREATMENT:
1. Dialysis
2. Renal transplant (especially in males)

TYPES:
1. Type I: Autosomal dominant (or recessive?). Juvenile onset of ESRD with SNHL
2. Type II: X-linked dominant. Juvenile onset of ESRD and SNHL
3. Type III: X-linked dominant. Adult onset ESRD and SNHL
4. Type IV: X-linked dominant. Adult onset ESRD, normal hearing
5. Type Va: Autosomal dominant (or recessive?). Nephritis, SNHL, macrothrombocytopathy - large platelets, and leukocyte inclusions (aka. Fechtner syndrome)
6. Type Vb: Autosomal dominant (or recessive?). Nephritis, SNHL, Macrothrombocytopathy (aka. Epstein syndrome)
7. Type VI: Autosomal dominant (or recessive?)

Question 119

Regarding Cowden disease, discuss:
1. Genetics and inheritance
2. Features

Answer 119

GENETICS:
1. Mutation in PTEN tumor suppressor on chromosome 10
2. Autosomal dominant
3. PTEN-hamartoma tumor syndromes

FEATURES:
1. Multiple hamartomas:
- Trichelimmomas (benign tumor arising from the outer root sheath of hair follicles. It appears as a warty or smooth papule on the face and neck region)
- Intestinal polyps
- Hamartoma of skin, breast, thyroid, and GI tract
2. Predisposition for cancers:
- Endometrial cancer
- Breast cancer
- Follicular thyroid cancer and follicular adenoma
3. Gingival Fibromatosis: oral papules involving lips, tongue (cobblestone appearance)

Vancouver notes Page 46

Question 120

What is a Hamartoma vs. Choristoma?

Answer 120

Hamartoma = overgrowth of normal tissue in a normal location (E.g. skin tag)

Choristoma = normal tissue in abnormal location (e.g. pancreatic tissue in duodenum; parotid tissue in temporal bone)

Question 121

What is a Mondini malformation? List 5 syndromes that are associated with this malformation.

Answer 121

= Cochlea is incomplete, with only 1.5 turns instead of 2.5

Syndromes associated:
1. Wildervanck
2. Waardenburg
3. Treacher Collins
4. BOR
5. Pendred

Question 122

What is Scheibe’s Aplasia? What are 4 syndromes associated with this?

Answer 122

= Cochleosaccular membranous aplasia (failure to develop)

1. JLN
2. Refsum
3. Usher
4. Waardenburg

https://entokey.com/congenital-malformations-of-the-inner-ear-2/

Question 123

Regarding Congenital Unilateral Lower Lip Palsy (CULLP), discuss:
1. What are the clinical features of this?
2. Associated anomalies and syndromes?
3. Management?

Answer 123

CULLP:
- Asymmetric crying facies due to congenital absence or hypoplasia of depressor anguli oris
- Or due to facial nerve compression (birth trauma, etc)
- Can be confirmed with US or EMG

Associated anomalies:
- 10% cardiac/renal anomalies
- Can be associated with 22q11 deletion
- Cayler syndrome: Asymmetric facies with cardiac defect

Management:
- From the lip perspective, will get better with time

Vancouver 499

Question 124

√Regarding Wildervank syndrome, discuss:
1. Inheritance and Genetics
2. Clinical features

Answer 124

INHERITANCE: X-linked
GENE: FGF13

FEATURES:
1. Klippel-Feil malformation (short neck, fused cervical vertebrae)
2. Brevicollis
3. Spina bifida assimilation of the atlas (basilar impression)
4. SNHL or mixed HL (Mondini and middle ear malformations)
5. CNVI paralysis with eye retraction on lateral gaze (“Duane retraction syndrome”)

Question 125

√Regarding Otopalatodigital syndrome, discuss:
1. Inheritance and Genetics
2. Features

Answer 125

INHERITANCE: X-linked recessive
GENE: FLNA, Xq28 mutation, Filamin A protein

FEATURES:
1. “Oto” CHL due to ossicular malformation
2. “Palato” Cleft palate
3. “Digital” Stubby/clubbed digits, wide space between 1st and 2nd toe

Other:
1. Craniofacial deformities (hypertelorism, supraorbital deformity, flat midface, small nose)
2. Short stature

Question 126

√Regarding Norrie Syndrome, discuss:
1. Genetics and Inheritance
2. Features

Answer 126

INHERITANCE: X-Linked recessive
GENE: Mutation in NDP gene, Xp11, Norrin protein (structurally similar to TGF-beta)

Features:
1. Ears: Progressive SNHL (2nd/3rd decade)
2. Occasional progressive mental deterioration
3. Eyes: Congenital/rapidly progressive blindness due to pseudoglioma, exudative vitreoretinopathy, opacification (cataracts), ocular degeneration