CommonPedSyndromes.pdf

Common syndromes seen in a craniofacial clinic

Anna H. Messner, MD Professor Otolaryngology/Head & Neck Surgery

and Pediatrics Stanford University

1. What syndrome does this child have?

1a. Bonus: what other syndrome is due to a defect of the same gene?

2. Does a child diagnosed with Pierre Robin sequence necessarily have a cleft palate?

3. What syndrome should be tested for?

  2-day-old with a weak cry.   Flexible exam reveals:

4. When looking at the eyes – how can the clinician tell the difference between Treacher-Collins syndrome and Goldenhar syndrome?

5. This ear is classic for what syndrome?

6. What is the item at the end of the arrow and what other physical findings will the child likely

have?

7. List 3 alternate names for Goldenhar Syndrome.

8. If a child develops velopharyngeal insufficiency after adenoidectomy what syndrome should you

test for?

9. A child with a history of cleft palate comes to your clinic- what syndrome does she most likely

have?

10. What syndrome does this child likely have?

Question?

What is the difference between a “sequence” and a “syndrome?”

Sequence: a pattern of multiple anomalies derived from a single anomaly or mechanical factor

Syndrome: a combination of symptoms that occur together so commonly that they constitute a distinct clinical picture.

Pierre Robin Sequence (Robin sequence; Pierre Robin malformation sequence)

1923 “Stomatologist” Pierre Robin

Micrognathia

Glossoptosis

Cleft palate (+/-)

http://www.pierrerobin.org

Pierre Robin Sequence

Airway obstruction:

1.  Posterior displacement of tongue due to micrognathia/retrognathia

2.  Loss of support of genioglossus muscle 3.  Development of negative pressure on

swallowing and inspiration resulting in glossoptosis

Pierre Robin Sequence

•  Levels of Obstruction: •  Nasopharynx- tongue herniates through palate and obstructs nasopharynx •  Oropharynx •  Hypopharyns •  Supraglottis

•  “supraglottic compression” •  Sidman 2001

Etiology: non-syndromic

•  Intrauterine Positional Deformation •  Oligohydramnios leads to chin tucked to chest and mandible restriction

•  Uterine crowding (twins), tumors •  Abnormal zygotic implantation sites.

Progression

Moore KL, editor. Before we are born: basic embryology and birth defects. 3rd edition. Philadelphia: WB Saunders: 1989 p134.

Courtesy of Glenn Isaacson, MD

Evaluation

•  Physical Examination (optional flexible scope exam) •  Micrognathia •  Cleft palate •  Prolapsed tongue

•  Respiratory effort •  Substernal retractions & supraclavicular muscle use •  Noisy breathing (stertor) •  apnea

•  Feeding status (prolonged, choking/coughing, desats, FTT) •  +/- Sleep study •  +/- pH probe

•  Increased intrathoracic pressures reversible GPR

Laboratory Evaluation

•  Blood gas- CO2 & Bicarbonate levels •  May be the best indicator of hypoxia/severity •  Levels may be high in relatively quiet child

Beware of the 1-2 week “honeymoon” period.

Severity of micrognathia

0-3 mm Normal 3-5 mm Mild 5-10 mm Moderate >10 mm Severe

** Weak correlation between severity of micrognathia and severity of symptoms**

Evaluation

•  Imaging: •  CT •  MRI

Acute Airway Management Prone positioning

Nasopharyngeal tube

CPAP

Laryngeal mask airway

Intubation – may need to be done through an LMA

Tracheostomy

Prone positioning goes against “Back to Sleep” •  AAP recommended nonprone position 1992 •  SIDS

•  unknown cause •  still responsible for more infant deaths in the US than any other cause of

death during infancy beyond the neonatal period. •  Increased risk with:

•  Side sleeping (compared to prone) •  Redundant bedding

•  Decreased risk with: •  Sleeping in same room as mother •  Pacifier

Mandibular Catch Up Growth

• Traditional teaching: • Extrinsic etiology/isolated Pierre Robin micrognathia will “catch up” in 6 mo – 4 years • Intrinsic (syndromic) micrognathia will not

Mandibular Catch Up Growth

• Multiple long-term studies have shown that even isolated PRS have significantly smaller mandibles over time:

• Long Term Longitudinal Mandible Development. Figueroa, 1991 • The mandibular catch-up growth controversy in Pierre Robin sequence. Daskalogiannakis, 2001. 96 patients, Case Control • Early Postnatal Development of the Mandible in Children with Cleft Palate and Nonsyndromic Pierre Robin Sequence (Case Control). Eriksen, 2006 • Craniofacial morphology and adolescent facial growth in Pierre Robin sequence. Suri, 2010 “No evidence of adolescent mandibular catch up growth”

Airway management: Nasal Trumpet

•  Requires frequent suctioning.

Airway Management: tongue-lip adhesion

1.  2. 2.

3. 4.

Bijnen et al. Tongue-lip adhesion in the treatment of Pierre Robin Sequence. J Craniofacial Surg 2009 20:315-320.

Tongue-lip adhesion (continued)

5.

6.

Bijnen et al. Tongue-lip adhesion in the treatment of Pierre Robin Sequence. J Craniofacial Surg 2009 20:315-320.

Airway Management- Mandibular distraction

Mandibular Distraction Osteogenesis

5 mo

8 mo

Airway Management- Tracheotomy

Robin Sequence- Feeding

•  Question: Can babies with Robin Sequence breastfeed?

Not if they have a cleft palate. (Babies are able to breastfeed with a cleft lip.)

Feeding protocol

Upright feeding technique

Modification of nipple

NG/OG feeding tube (gavage feeds)

Gastrostomy tube

Haberman Feeder

Robin Sequence

•  115 patients (1962-2002) •  Non-syndromic 54% •  Stickler syndrome 18% •  Velocardiofacial syndrome 7% •  Treacher Collins syndrome 5% •  Facial and hemifacial microsomia 3%

•  Evans AK, Rahbar R, Rogers GF, Mulliken JB, Volk MS. Robin sequence: a retrospective review of 115 patients Int J Pediatr Otorhinolaryngol 2006 70:973

•  Percentages likely much different now due to improved genetic analysis!

Stickler Syndrome: The Basics

•  Progressive, genetic connective tissue disorder •  Autosomal dominant •  High degree of penetrance •  Wide range of severity/ expression •  Affects both sexes/ all ethnicities •  Believed to be the most common connective tissue

disorder

•  Stickler Involved People •  http://sticklers.org http://sticklervideo.org

Stats and Specs

•  Mutations found in three collagen genes to date •  Prevalence between 1 in 7500 and 1 in 3300 •  Frequently misdiagnosed or undiagnosed

•  Average age of children diagnosed - 4.2 years •  Average age of adults diagnosed - 32 years •  One study found 53% error rate in original diagnosis of patients later

determined to have Stickler syndrome •  12% of children diagnosed at birth with Pierre-Robin sequence were

later found to have Stickler syndrome •  Problems with vision, hearing, bones/ joints and oro-facial

features

Stickler Syndrome Diagnostic Criteria

Stickler syndrome

•  Characteristics •  Ocular problems: 95% retinal detachment in 60%, myopia in 90%,

blindness 4% •  84% facial abnormalities (flat nose, small mandible, cleft palate,low set

ears) •  70% hearing loss (SNHL & CHL, hypermobile TM’s) •  90% degenerative joint disease and pain

Clinical Findings – Ocular

Myopia (mild to severe) Present at birth Minimal progression

Retinal Detachment/Degeneration Spontaneous Giant tears/ holes Bilateral Patient typically under age 30

Cataracts Pre-senile Wedge or comma shaped Vitreous anomalies/degeneration Glaucoma Astigmatism/ Strabismus

Clinical Findings - Auditory

Sensorineural hearing loss Conductive hearing loss Otitis media Hypermobile tympanic membranes Ears tend to be low set

Clinical Findings - Oro-facial

Flat malar/ mid-face area Small lower jaw/ micrognathia Posterior-placed tongue Obstructive airway complications Cleft palate, submucous cleft or high arched palate Bifid uvula Flat nasal bridge Small, “button” nose

Stickler Faces

What syndrome is associated with lip pits?

Van Der Woude syndrome

•  Autosomal dominant •  Mutation in the IRF6 gene (spectrum of disorders Van der Woude

syndrome popliteal pterygium syndrome).

•  Diagnosis •  Lip pits and cleft lip and/or cleft palate •  Lip pits and first-degree relative with CLP •  Clp and a first-degree relative with lip pits

•  Popliteal pterygium syndrome •  CL and/or palate w/ lip pits •  Webbing of skin •  Syndactyly •  Genital anomalies •  Syngnathia •  Eyelid abnormalities

Photo courtesy of Mary Hauk, DDS

Velocardiofacial syndrome

1960’s Endocrinologist Angelo Digeorge, MD • Hypoparathyroidism • Hypoplastic thymus • Conotruncal heart defects • Cleft lip &/or palate

• DiGeorge Syndrome

1970’s Speech pathologist Robert Shprintzen, PhD • Cleft lip &/or palate • Conotruncal heart defects • Absent/hypoplastic thymus • Hypocalcemia

• Schprintzen syndrome • Velocardiofacial syndrome

Chromosome deletion 22q11.2

Also known as:

•  Sedlačková syndrome •  Conotruncal anomalies face syndrome •  Takao syndrome •  Cayler syndrome •  22q11 deletion syndrome •  CATCH 22 syndrome (not considered appropriate)

www.vcfsef.org

Velocardiofacial Syndrome

  C ardiac   A bnormal facies   T hymus deficiency   C left palate   H ypocalcemia   22

Syndrome(s) associated with laryngeal web

  Velo-cardio-facial syndrome/DiGeorge syndrome

  Abnormalities of Chromosome 22q11

  Miyamoto RC, Cotton RT, Rope AF et al Otolaryngol Head Neck Surg 2004 130:415-7.

Features (180 phenotypes)

•  Congenital heart defects (49-83%) •  Tetrology of Fallot, interrupted aortic arch, VSD, vascular rings

•  Palatal abnormalities (69-100%) •  submucous cleft palate, occult SMCP

•  Velopharyngeal insufficiency (27-92%) •  Vascular anomalies •  Speech and language impairment (79-84%) •  Early feeding problems •  Genitourinary anomalies (36-37%) •  Hypocalcemia (17-60%) •  Psychiatric disorders (9-50%) •  Immune disorders •  Opthalmologic disorders (7-70%)

Diagnosis

Fluorescence in situ hybridization (FISH) Microdeletion is present in 1/2000-1/4000

Shprintzen R. Dev Disabil Res Rev 2008;14(1):3-10

Auricular characteristics

•  Overfolding helix •  Cup ear •  Protruding ears •  Attachment of lobules •  Narrow external auditory canals

•  Butts SC. Int J Pediatr Otorhinolaryngol 2009 73:343.

Nasal characteristics

•  Bulbous nasal tip •  Widened nasal dorsum •  Hypoplastic nasal alae

Butts SC. Int J Pediatr Otorhinolaryngol 2009 73:343

Midface

Malar flattening Elongated lower facial height

Shprintzen R. Dev Disabil Res Rev 2008;14(1):3-10.

Persistent velopharyngeal insufficiency postadenoidectomy

•  23 patients with velopharyngeal insufficiency following adenoidectomy

•  14 patients tested for 22q11 deletion •  9 positive with 5 having phenotypic VCFS

SO: 1)  If VCFS do adenoidectomy with caution 2)  If VPI after adenoidectomy- consider testing for 22q11 deletion-

even if no clinical evidence of VCFS.

Perkins JA, Sie K, Gray S. Arch Otolaryngol Head Neck Surg. 2000 126:645.

Velopharyngeal insufficiency and VCFS

Treacher-Collins Syndrome (Franceschetti-Zwahlen-Klein syndrome)

Defect of: 1st & 2nd pharyngeal arches

TC syndrome- physical characteristics

•  Midface hypoplasia (89%) •  Downward sloping palpebral fissures •  Micrognathia and retrognathia (78%) •  Lower eyelid abnormalities

•  Coloboma (69%) •  Absent lashes (53%)

•  Microtia (36%) •  Conductive hearing loss due to ossicular abnormalities •  Ophthalmalogic (vision) defects •  Preauricular hair displacement (26%) (hair grows in front of ear) •  Cleft palate (28%) •  Choanal atresia/stenosis

Treacher-Collins—Autosomal dominant TCOF1 gene

TCS

•  40% of patients with TCS have a affected parent •  60% of probands with TCS have a de novo gene mutation

Oculoauriculoverterbral spectrum Hemifacial microsomia

Craniofacial microsomia Goldenhar’s syndrome

1st & 2nd Branchial arch syndrome

•  WIDE variability - Usually unilateral (85-90%) and on right side - Both autosomal recessive and autosomal dominant inheritance described.

Possible Origin

•  Vascular injury to the stapedial artery injuring the 1st & 2nd Branchial arches

OAV spectrum

Physical findings Ocular and ear anomalies Hemifacial microsomia Epibulbar dermoids

Upper eyelid colobomas Macrosomia Facial clefts Ear malformations Vetebral malformations

Unique physical findings

Epibulbar dermoids

Upper eyelid coloboma

Mandibular deficiency

Classification of Pruzansky Type 1: Mild hypoplasia of the ramus (nl body) Type 2: Condyle and ramus are small, head of condyle is flattened,

glenoid fossa is absent, coronoid process may be absent. Modification by Mulliken and Kaban Type 2a: glenoid fossa-condyle relationship nl and TMJ functional Type 2b: glenoid fossa-condyle relationship NOT normal and TMJ is nonfunctional

Type 3: Ramus is reduced to thin lamella of bone or is completely absent, no evidence of TMJ

http://scienceblogs.com/

CHARGE syndrome

C oloboma H eart defects A tresia of nasal choanae R etarded growth and development G enital and/or urinary defects E ar anomalies and/or deafness

Clinical Diagnostic Criteria (2005) (Major features: very common in CHARGE and relatively rare in other conditions)

Major features: Coloboma of iris, retina, choroid, macula or disc (not eyelid),

micropthalmos, anopthalmos (80-90%)

CHARGE syndrome (major features)

Pinna abnormality: short, wide ear with little or no lobe, prominent antihelix, triangular concha, decreased cartilage, asymmetric (>50%)

http://www.chargesyndrome.org/

CHARGE: Major features

Choanal atresia (50-60%) Cranial nerve abnormality

Missing or decreased sense of smell (90-100%) IX/X- swallowing difficulties (70-90%) VII- facial paralysis (40%)

CHARGE: minor features

Hockey stick palmer crease

Major features:

Ear: Ossicular malformation (conductive hearing loss) Malformed cochlea, small or absent semicircular canals (SNHL)

CHARGE: minor features (significant, but more difficult to diagnose or less specific to CHARGE)

•  Heart defects •  Cleft lip/palate •  TEF •  Kidney abnormalities •  Genital abnormalities •  Growth hormone deficiency •  Perseverative behavior in younger individuals, obsessive

compulsive behavior in older individuals


•  Typical facies: •  square face •  broad prominent forehead, •  arched eyebrows, •  large eyes, •  occasional ptosis, •  prominent nasal bridge with

square root, thick nostrils, •  prominent nasal columella, flat

midface, small mouth, facial asymmetry

CHARGE


Hockey stick palmer crease

CHARGE: other features

•  Chronic ear problems (85%) •  Hypotonia •  Sloping shoulders •  Limb/skeletal anomalies •  CNS abnormalities •  Thymus or parathyroid abnormality •  Omphalocele •  Nipple anomalies •  Hypotonia (90%) •  Scoliosis

CHARGE: genetics

•  Abnormality in long arm of Chromosome #8 (CHD7) •  Present in 70% of CHARGE patients •  New mutation in dominant gene

•  Reoccurence risk in parents 1-2% •  Risk to children of CHARGE parents 50%

1. What syndrome does this child have?

1a. Bonus: what other syndrome is due to a defect of the same gene?

Van der Woudes syndrome

Popliteal ptergium syndrome

2. Does a child diagnosed with Pierre Robin sequence necessarily have a cleft palate?

No.

3. What syndrome should be tested for?

  2-day-old with a weak cry.   Flexible exam reveals:


4. When looking at the eyes – how can the clinician tell the difference between Treacher-Collins syndrome and Goldenhar syndrome?

TCS- coloboma is present in the lower eyelid Goldenhar syndrome- coloboma is in the upper eyelid

5. This ear is classic for what syndrome?

CHARGE syndrome

6. What is the item at the end of the arrow and what other unusual physical findings will the child

likely have?

Coloboma- seen in OAVS- other features include hemifacial microsomia, upper eyelid coloboma, microtia, micrognathia

7. List 3 alternate names for Goldenhar Syndrome.

Oculoauriculoverterbral spectrum Hemifacial microsomia Craniofacial microsomia 1st & 2nd Branchial arch syndrome

8. If a child develops velopharyngeal insufficiency after adenoidectomy what syndrome should you

test for?


9. A child with a history of cleft palate comes to your clinic- what syndrome does she most likely

have? Stickler syndrome

10. What syndrome does this child likely have?

CHARGE syndrome

The End!

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CommonPedSyndromes.pdf

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