Pediatric Syndromes and Vascular Malformations

Arise from failure of thyroglossal duct obliterate at around 5th to 8th week of gestation.

• Proximally: forament caecum
• Distally: pyramidal lobe of thyroid and anywhere in the midline between the two

• No sex predilection
• <1% midline
• 1/3 present as submental or low cervical masses
• Usually <2 cm

Papillary thyroid carcinoma

• Sistrunk procedure:
• Excision of portion of hyoid bone + cyst + proximal trunk to base of tongue.

• 8 disorders:
• FGFR1: Pfeiffer syndromes
• FGFR2: Apert syndrome, Beare-Stevenson syndrome, Crouzon
• FGFR3: Crouzon with Acanthosis nigricans, FGFR3-related isolated coronal synostosis, Muenke syndrome)

Autosomal dominant manner

• Premature fusion of sutures
• Abnormal shape of skull
• Restricted brain growth
• Increased intracranial pressure
• Hydrocephalus
• Intracranial hypertension (esp. Crouzon Syndrome)

• Midface hypoplasia
• Diminished nasal and nasopharyngeal spaces
• Forced mouth breathing of infants
• Elongated and ptotic palate (Apert syndrome)
• Central, obstructive, and mixed sleep apnea

• Dental and oral anomalies
• High-arch palate with constricted width (Apert Syndrome)
• Clefting (submucous, incomplete, complete)
• Delayed dental eruption
• Limited maxillary alveolar bone
• Severe crowding
• Angle Class III bite

• Crouzon: conductive due to aural atresia, SNHL
• Pfeiffer: OME, meatal atresia, ossicular fixtion
• Apert: otitis media common, cleft palate can result in eustachian disorder; Congenital fixation of stapedial footplate

Family of metabolic disorders caused by deficiency of lysosomal enzymes needed to degrade glycosaminoglycan

• Type I – Hurler Syndrome (most common MPS)
• Type II (aka Hunter Syndrome)
• Type III – Sanfilippo (A, B, C, D subtypes)
• Type IV – Morquio (A, B)
• Type VI – Maroteaux-Lamy syndrome
• Type VII – Sly syndrome (beta-glucuronidase deficiency)
• Type IX – Natowicz syndrome (hyaluronidase deficiency)

• Hurler Syndrome (most severe)
• Hurler-Scheie Syndrome
• Scheie Syndrome (lease severe)

• Facial dysmorphism (coarse facial features, scaphocephalic, frontal bossing, depressed nasal bridge)
• Hypertelorism
• Corneal clouding
• Hepatomegaly
• Valvular heart disease
• Developmental delay
• Hearing Loss
• Skeletal deformities
• Phalangeal dysostosis, synovial thickening, joint stiffness

• Hunter Syndrome
• X-linked Recessive
• Chromosome 10
• Iduronate sulfatase deficiency
• Type A and B

• Chromosome 4
• Alpha-L-iduronidase deficiency
• Increased urinary heparan sulfate and dermatan sulphate
• Autosomal recessive
• 1/100,000

Fissure between the laryngotracheal and pharyngoesophageal systems

Benjamin and Inglis Classification

• Type I – supraglottic interarytenoid
• cleft ABOVE level of TVC
• Type II – cleft extends below the
• TVC into the upper cricoid cartilage
• Type III – cleft extends through the
• cricoid cartilage +/- extension into cervical trachea (extrathoracic)
• Type IV – cleft extends into the
• thoracic trachea and extends toward the carina (intrathoracic)

Submucosal cleft

• 0.5% to 1.6 of laryngeal abnormalities (rare)
• Males > Females
• 60% seen in conjunction with other abnormalities (TEF, tracheomalacia)

• Swallowing - aspiration, cyanosis with feeding
• Pharyngolaryngeal - stridor, toneless cry, weak cry, pharyngeal hypersecretions
• Respiratory - dyspnea, recurrent aspiration, respiratory distress

• G Syndrome
• Pallister Hall Syndrome
• VACTERL
• CHARGE

• Brachycephaly
• Upslanting palpebral fissures
• Brushfield spots
• Flat facial profile
• Small nose and depressed nasal bridge

• Mental retardation (variable IQ)
• Hypotonia
• Ligamentous laxity
• Congenital heart disease (50% - AVSD, VSD)
• Single palpar crease
• Hypothyroidism, leukemia, duodenal atresia, Hirschsprung

• Small ears
• Narrow EACs
• Increased glue ear
• Non-reproducible OAEs
• Abnormal ossicles
• Mixed HL, SNHL

• Macroglossia
• Airway obstruction from small psoterior nsal spine
• Large tonsils and adenoids
• Smaller subglottis
• Unstable atlanto-occipital joint

• Cleft palate
• Retrognathai and micrognathia
• Airway obstruction
• Small open mouth
• Prominent nose with squared-off nasal tip

• Autosomal dominant
• TCOF1 gene
• High proportion sporadic / new mutations

• Bilateral, symmetric and congenital:
• Microtia, dysplastic ears
• Auricular pits/fistulas/tags
• CHL (aura atresia, malformation of ossicles)
• Micrognathia
• Mandibular hypoplasia
• Cleft palate

• Flat malar region
• Prominent nose
• Broad mouth
• Narrow nasopharynx
• Choanal atresia (rare)

• Downslanding palbebral fissures
• Coloboma of inferior eyelid
• sparse eyelashes

• Oculo-auriculo-vertebral syndrome
• Hemifacial microsomia
• First and second arch syndrome

• Microtia
• Pre-auricular skin tags
• Skin tags
• Deafness
• Macrostomia (+/- lateral facial clefting)

• Colboma
• Heart defect
• Atresia chonae
• Retardation of growht
• Genital defect
• Ear anomalies

• 1/12,000
• Mutation in gene CHD7 in 65% of cases
• Most due to new mutations

• Ossicular abnormalities
• Protruding, asymmetric pinna
• Temporal bone abnormlaities (absent or hypoplastic SCCs)
• SNHL (mild to profound)

• Autosomal dominant
• EYA1 gene mutations
• Less commonly SIX-1 gene

• Prehelical pits, dysplastic pinna
• CHL (ossicular chain malformations)
• SNHL (modini dysplasia, dilated vestibular aqueducts)
• Mixed HL
• Branchial fistulae or cysts

• Duplex collecting system
• Hydronephrosis
• Dysplastic kidnes
• Unilateral or bilateral renal agenesis

• 22q11.2 Deletion syndrome
• Velocardial facial Syndrome
• Shprintzen syndrome

• Microdeletion syndrome
• Autosomal dominant
• Variable penetrance
• 90% from new mutations (de novo deletion)

• Overt or submucous cleft palate
• VPI
• Hypernasal speech

• Small, low-set ears
• Prominent/overfolded helices
• Absent or hypoplastic ear lobules
• Pre-auricular tags
• Otitis media
• SNHL
• Narrow EACs

• Upper airway obstruction
• Laryngeal web
• Vascular Ring
• Laryngomalacia

• Prominent nasal bridge, bulbous nose, long face
• CHD
• Mental retardation, developmental delays
• Short stature
• Feeding difficulties
• Psychiatric illness
• Immune deficiency
• Hypocalcemia secondary to parathyroid dysfunction

• X-linked mutations
• Collagen IV
• Can also have autosomal recessive and dominant forms

• High-tone SNHL (mild to moderately severe)
• 83% of males
• 57% of females
• Progressive deterioration during school-age

• 1. Bilateral vestibular schwannomas
• 2. First degree relative with NF2 and unilateral vestibular schwannoma OR
• Two of: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities
• 3. Unilateral vestibular schwannom AND two of above
• 4. Multiple meningomas AND unilateral vestibular schwannoma

• Infantile
• - Single, multiple
• - Reticular

• Congenital
• - RICH
• - NICH
• (but infantile hemangiomas can have a "herald" lesion at birth)

• Benign tumour of the endothelium
• Are acquired vascular lesions
• Most common tumour of infancy
• Risk factors: Cacucasion, prematurity, female

• 80% single versus 20% multiple
• 60% involve head and neck
• 25% involve trunk

• 3 phases:
• Proliferative (usually achieves 80% of size by age 3; typically rapid growth in first 4 weeks)
• Involuting phase
• 50% involute by 5 years, 70% by 7 years, and 90% by 9 years
• Involuted (involution has completed) - residual hemangiomas/telangiectasias may be present

• Ulcerated lesions
• Injury to hair follicles leading to alopecia
• Descruction of near by tissue
• Periorbital lesions can cause ambylopia
• Occlusion of EAC - otitis externa
• Subglottic hemangioma causing airway obstruction

Liver, lung, GI

• Rapidly involuting congenital hemangioma
• Proliferates in Utero and is fully developed at birth
• Completely involute during the second year of life

• Affects 2.3% of people with infantile hemangioma
• Plaque-like IH in a segmental or trigeminal dermatomal distribution
• P = Posterior fossa brain malforamtion
• H = hemangioma
• A = arterial cerebrovascular anomalies
• C = Coarctation of the aorta/cardiac defects
• E = eye and endocrine abnormalities

8% have stroke in infancy; 42% have structural brain abnormality

• Observation for 90% that are small, not affecting aesthetics
• Woundcare for ulcerated hemangiomas (e.g. anogenital, labial, neck)
• Topical corticosteroid - minimal efficacy
• Intraleasional corticosteroid - effective for small, well-localized IH
• Systemic corticosteroid - avoid if possible, can have rebound proliferation
• Propranolol - no RCTs, but effective in proportion of patients; no protocol
• Embolization for large lesions causing high-output congestive heart failure

• Excessive bradycardia (ensure pt does not have prolonged QT)
• Bronchospasm
• Hypoglycemia
• Headaches
• Hypotension

• Pulse-dye laser is CONTRAINDICATED during the proliferative phase
• - poor penetration, can cause skin atrophy, hypopigmentation

Used during involuted phase to treat RESIDUAL telangiectasias

Limited due to high risk of bleeding, destruction of surrounding structures

Usually reserved for management of residual fibrofatty tissue, redundant skin, or damaged structures after involution

Indicated if:well localized, anatomically safe, and lesion causing significant issue (e.g. ulceration, alopecia)

• Different appearance from IH:
• It is red-violaceous, course telangiectasias
• Central pallor
• Peripheral pale halo
• More common in extremities; equal sex distribution, solitary

• RICH and NICH
• RICH = rapidly involuting
• NICH = non-involuting

• Infantile Hemangioma
• Congenital Hemangioma
• Kaposiform hemangiomendothelioma (KHE)
• Pyogenic granuloma

• Benign, locally aggressive vascular neoplasm
• Does NOT metastasize
• Develops during infancy
• Occurs in ages 1 to 10
• Equal sex distribution
• Solitary, inolves head/neck > tunk > extremity
• 50% have KMP (Kasabach-Merrit Phenomenon of thrombocytopenia, petechiae, bleeding)
• Medical treatment with vincristine is first-line

• Asympatomatic during first weeks of life
• Present during proliferative phase (6 to 12 weeks)
• Biphasic stridor
• Respiratory distress
• Normal voice
• Normal swallowing
• Difficulty feeding
• Cough can mimic croup

• 50% of those with SGH have infantile Hemangioma
• 5 to 9% of those with infantile hemangioma will have SGH

Endothelial cells with high GLUT1 (erythrocyte-type glucose transporter) expression

Will see endothelial cells, pericytes, fibroblasts, interstitial cells, and mast cells on histology

• Systemic Steroid
• Interferon alpha-2a (antiproliferative angent that inhibits angiogenesis)
• - Sideeffects: fever, myalgia, hepatic trasaminitis, transient neutropenia, spastic diplegia
• Tracheostomy only for refractory cases
• Endoscopic laser resection (CO2) is successful in 90%
• - but high rate of subglottic stenosis

• Primary (tracheal dyskinesia)
• Secondary
• - Esophageal atreasia +/- TEF
• - External compression by:
• Cardiac/vascular anomaly
• Mediastinal mass/tumour

• Complete rings (double aortic arche, Neuhauser anomaly)
• Incomplete rings (innominate artery, retroesophageal right subclavian, aberrant left pulmonary artery)
• Dilatation of the pulmonary arteries and left atrium

• Type I - Congenital or intrinsic tracheal abnormalities (+/- TEF)
• Type II - Extrinsic defects of anomalies
• Type III - Acquired tracheomalacia (prolonged intubation, chronic tracheal infections, inflammatory conditions - polychondritis)

• Expiratory stridor after a few weeks of life ("laryngeal crow")
• - worse with supine position, crying, and respiratory infections

• Feeding difficulties
• Hoarseness, aphonia, and breathing
• History of: prolonged intubation, tracheostomy, chest trauam, recurrent tracheobronchitis, cartilage disorder, lung resection

• Type of vascular malformation
• Theories include:
• - failure of lymphatic system to separate from venous system
• - dysregulation of lymphatic endothelial cell growth

• 75% in the head and neck
• 50 - 60% diagnosed antenatally or at birth
• Other common areas: axilla, abdominal wall
• If later presentation, likely due to trauma or infection

• MRI
• T1 shows non-henahncing signal similar to muscle signal
• T2 shows nonenhanced high signal; without feeding and draining vessels seen in hemangiomas

Microcystic - <2 cm cystic spaces; bilateral, suprahyoid; higher cmplication and lonterm sequelae rates

Macrocystic- >2 cm cystic spaces, unilateral, infrahyoid; better response rates to surgery or sclerotherapy

• Turners
• Down Syndrome
• Patau Syndrome
• Trisomy 13

• Large bilateral "beard distribution" malformations
• mucosal involvement

• Primary bone involvement; mandibular deformities
• Tongue involvement causing hypertrophy and bleeding (airway compression, feeding and speech issues)
• Parotid and FOM involvement

• Conservative may be appropriate for favourable lymphatic malformations (unilocular, macrocystic posterior lateral can involve spontaneously)
• Sclerotherapy
• Surgery especially for macroystic lesions in the posterior inferior neck
• Systemic steroids and antibiotics to treat infection

• OK-432
• Doxycycline
• Bleomycin (can cause pulmonary fibrosis_
• Ethanol (nerve injury)
• Sodium tetradecyl sulfate

• lyophilized low-virulence GAS pyogenes
• inactivated by heating with penicillin

• Vascular malformation
• Usually has blueish overlying skin or mucosal hue
• Compress easily
• Enlarge with valsalva maneuver
• Present at birth
• Growth triggered by trauma, infection, and hormonal influences

Bright signal on T2 imaging

• Fast flow lesions with direct AV shunting
• Triggered by infection, trauma, or hormonal chnages
• Classified into four potential stages:
• dormancy, expansion, destruction, and heart failure