Review of Otolaryngology related Pediatric Syndromes David E. Karas MD Connecticut Pediatric Otolaryngology Yale New Haven Children’s Hospital Yale School of Medicine

Disclosures Speaker’s Bureau for Alcon

Syndromology Major Minor Significant functional or cosmetic impact Heart defect, abnormal brain formation, cleft lip/palate Minor No major functional or cosmetic impact

Etiology Environmental (Teratogenic) Chromosomal Alcohol exposure Single gene Multiple gene

Patterns Sequence Syndrome Association Multiple defects from a single malformation Pierre Robin Syndrome All components are pathologically related Trisomy 21 or Fetal Alcohol Association Occur together more frequently VATER/VACTERL CHARGE

Branchio-Oto-Renal (Melnick-Fraser) Branchial cleft sinuses Hearing Loss Sensorineural but may be mixed Renal Dysplasia (12-20%) Autosomal Dominant 1 in 40,000 Births Variable penetrance Associatied with 8q Facial Palsy/Lacrimal duct

Treacher Collins (Mandibulofacial Dysostosis) Autosomal Dominant 1 in 50,000 births 5q Abnormal structures of 1st and 2nd Branchial arches, grooves and pouch. Small, absent, or low set ears Micrognathia Cleft Palate (35%) Normal Intelligence

Nagers(Acrofacial Dysostosis) Malar Hypoplasia Down-slanting palpebral fissures Absence of lower eyelashes Atretic External Auditory Canals Conductive Hearing Loss Normal cognition and development Localization to 9q Limb abnormalities, particularly absent thumbs

Velo-Cardio-Facial(Shprintzen) High Arched/Cleft palate Broad nasal root Cognitive impairment Cardiac anomalies Velopharyngeal Insufficiency (VPI) Immunologic deficiencies 22q11 deficiency, Autosomal Dominant Feeding difficulties Hypocalcemia

Down’s Syndrome Trisomy 21 Stenotic ear canals/Low set ears COME/Eustachian tube dysfunction Middle ear anomalies Delayed Speech Obstructive Sleep Apnea Macroglossia Narrowed subglottis/trachea Cardiac defects

Mucopolysaccharidoses Lysosomal Storage Disease 7 distinct types Hurlers, Hunters, Sanfillipo Morquio, Maroteaux-Lamy Coarse facial features AIRWAY ISSUES!!!!! Obstructive Sleep Apnea Enzyme Replacement for types I,II, and VI

CHARGE Syndrome Coloboma Heart Anomalies Atresiae Chonae Retardation Genital Anomalies Ear Anomalies ~60% defect of CHD7 gene(chromosome 8)

VATER(VACTERL) Association Vertebral Anomalies Anal Cardiac defects Tracheo-esophageal Fistula Renal/Radial anomalies Limb defects No specific genetic pattern or inheritance Incidence 16/100,000 Vertebral (70%) Scoliosis later in life Anal defects (55%) Cardiac (75%) VSD/ASD/TOF TE fistula (70%) Renal (50%) 35% have a single umbilical artery 70% have radial defects frequently displaced or aplastic thumbs, polydactyly and syndactyly

Stickler’s Syndrome Midface Hypoplasia Cleft palate (Pierre Robin) Depressed Nasal Bridge Hearing Loss (15%) Dental Anomalies Mitral Valve Prolapse Genetic Sequencing is available Joint dysplasia/ hyperextensibilty

Kartagener’s Syndrome Immotile Cilia Situs Inversus Sinusitis Bronchitis/bronchiectasis Otitis Media Autosomal Recessive Genetically heterogenous

Craniosynostosis Crouzon’s Apert’s Saethre-Chotzen Pfeiffer Midface hypoplasia, coronal suture synostosis Apert’s Bicoronal synostosis, midface hypoplasia, orbital hypertelorism, polydactyly Saethre-Chotzen Bilateral coronal synostosis , variable midface hypoplasia, low set hairline , cleft palate Pfeiffer Multiple types with synostosis and most with limb abnormalities crouzon’s 15% atretic canals 55% conductive hearing loss

Syndromes More prevalent than you think Look for abnormalities minor malformations may indicate that major ones may also exist More than one family member may be affected Identification should not be underestimated Better care Better counseling Better Surveillance