Table 1.

Summary of the most common craniofacial syndromes and their association with OSA.

SYNDROME	EXTRA-ORAL FEATURES		INTRA-ORAL FEATURES	ASSOCIATION WITH OSA
Down’s syndrome 1:700 Genetics: Trisomy 21+ mutation in GATA1 gene [10]	Face ▪ lat nasal bridge ▪ Small ears ▪ Epicanthic folds ▪ Up slanting palpebral fissures Cranium ▪ Flat cranial base (N-S-Ba angle)	Maxilla ▪ Hypoplastic ▪ Deficient development of length, depth, height but usually not width of palate ▪ High V-shaped palate	▪ Macroglossia ▪ Microdontia of primary and permanent dentition ▪ Clinical crowns may be conical, shorter and smaller than normal and roots shorter ▪ Hypotonic perioral musculature ▪ Descending angles of mouth ▪ Everted lower lip w. tongue protrusion ▪ Mouth breathing ▪ Xerostomia	OSA prevalence [11,12,13,14,15] Childhood: 50–100%, Adulthood: 100% Predisposing factors—related to the syndrome: Macroglossia, adenotonsillar hypertrophy, midface hypoplasia, other associated conditions such as obesity, hypothyroidism, hypotonia, and gastroesophageal reflux [16]
Goldenhar syndrome 1:3500 to 1:7000 Genetics: MYT1 [17]	Face ▪ Hemifacial microsomia ▪ Anterior-posterior and vertical dimensions reduced on affected side ▪ Lateral facial cleft ▪ Macrostomia Eyes: ▪ Epibulbar dermoids ▪ Narrowing of palpebral fissures ▪ Vertical dislocation of orbit ▪ Microphthalmia/anopthalmia ▪ Upper eyelid colobomas	Ears ▪ Pre-auricular tags ▪ Deformities of pinna ▪ Microtia (small external ear)/anotia ▪ Hearing loss Vertebral anomalies ▪ Scoliosis ▪ Abnormal rib structure (missing or fused) ▪ Hemi vertebrae and cervical fusion	▪ Micrognathia ▪ Hypoplasia of maxilla and mandible ▪ High arched palate ▪ Delayed tooth eruption ▪ Supernumerary/missing teeth ▪ Enamel and dentin malformations ▪ Gingival hypertrophy ▪ CLP	OSA prevalence Up to 67% [1] Predisposing factors related to the syndrome: Maxillomandibular hypoplasia, glossoptosis, and abnormal control of breathing in patients with neurological compromise [18].
Cerebral Palsy 1 in 322 [19] Genetics: GAD1 on chromosome 2q31 [10]	Depends on the type and severity: ▪ Impaired motor control ▪ Delayed motor development ▪ Spastic muscles ▪ Difficulty walking	▪ Drolling ▪ Difficulty swallowing ▪ Ataxia ▪ Seizures	▪ Tongue thrust ▪ Mouth breathing ▪ Oral mucosa hypersensitivity ▪ Delayed eruption of permanent teeth ▪ Enamel hypoplasia ▪ Increased risk of dental caries ▪ Dental erosion	Risk of OSA: 38–55% [20] Predisposing factors—varies between CP types: Abnormal muscle tone, inability to change position on bed and as a side effect of some medication “for those with epilepsy” [21]
Pierre Robin Sequence syndrome 1: 8500–14,000 Genetics SOX9, COL2A1 [10]	Cardiac: Cor pulmonale (right side heart failure) Ears: infections/hearing loss ear Mandible: Retrognathia		Triad of: 1. Cleft palate (U-shaped) 2. Mandibular retrognathism—but will still grow 3. Glossoptosis ▪ Posterior displacement of the tongue ▪ Lack of support of the tongue musculature ▪ Airway obstruction ▪ Hypodontia	OSA prevalence 85–100% [22,23] Predisposing factors related to the syndrome: Mandibular retrognathia Mechanical collapse of the pharyngeal wall [24]
DiGeorge syndrome 1:4000–7000 Genetics:TBX-1 [10]	CATCH 22 Cardiac defects (Tetralogy of Fallot) Abnormal facial features Thymic hypoplasia Cleft palate Hypocalcemia Craniosynostosis	Eyes: Ocular hypertelorism, hooding of upper lids, ptosis, tortuous retinal vessels. Nose: prominent nasal base, bulbous nasal dimples. Ears: over folded, microtic ears, pre auricular pits.	Enamel defects Hypomineralization Higher risk of dental decay	OSA prevalence 10.2% [25] Predisposing factors related to the syndrome: Micrognathia and VPL surgeries
Treacher–Collin syndrome 1:25,000, 50,000 Genetics: Loss of function in gene TCOF-1 located on chromosome 5 [10]	Face Hypoplastic Zygoma Depressed cheeks Narrow face Mandible Underdeveloped mandible with retrusive chin Hypoplasia of condylar and coronoid processes Steep mandibular plane Prominent antegonial notching	Eyes Downward slanting palpebral fissures 75% have coloboma (notch on outer eyelid) Ears Deformed or displaced pinnae Extra ear tags Ossicle defects or absence of EA canal causing conductive hearing loss	Class II Malocclusion Open bite High arched palate Cleft palate in 30% of cases	OSA prevalence 29–95% [26,27] Predisposing factors related to the syndrome: Narrowing of the upper airway due to mandibular retrognathia and choanal atresia [28].
Prader–Willi syndrome 1:10,000–25,000 Genetics mutation chromosome 15q11-q13 [10]	Face Narrow bifrontal diameter Round face Eyes Almond-shaped eyes,	Others Small hands and feet Rapid weight gain Hyperphagia Hypogonadism	Downturned corners of the mouth Dental caries Enamel defects Tooth wear	OSA prevalence 44% to 100% [29,30] Predisposing factors related to the syndrome: Increase in viscosity of secretions Craniofacial abnormalities causing small airways, Hypotonia leading to airway collapsibility [31]
Apert syndrome 1:65,000–160,000 Genetics FGFR2 on chromosome 10q26 [10]	Cranium: Acrobrachycephally (tower skull) Kleeblatt-schadel (cloverleaf) Frontal bossing and tall forehead Eyes: Ocular proptosis Hypertelorism Downward slanting palpebral fissures Vision loss	Ears Middle ear infection Conductive hearing loss Maxilla Midface deficient = class III Limbs Syndactyly of 2nd, 3rd, and 4th digits and toes, 1st and 5th may be separate or joined	V-shaped arches Upper crowding Anterior open bite with posterior crossbite 75% have cleft of SP or bifid uvula Trapezoidal shaped lips Increased gingival thickening may be associated with Delayed eruption of teeth Shovel shaped incisors	OSA prevalence 81% [31] Predisposing factors related to the syndrome: Decreased size of nasopharynx Narrowing of post choanae = respiratory distress Increased mouth breathing = open mouth appearance
Achondroplasia 1:15,000–40,000 Genetics: FGFR 3 [10]	Body Dwarfism Short limbs Short fingers and toes Facial Underdeveloped midface Flattened nasal bridge	Ears: Increased ear infections Cranium: Hydrocephalus Short post cranial base	Retrognathic maxilla Normal mandible Protrusive maxillary incisors Anterior open bite Posterior crossbite Anterior reversed overjet	OSA prevalence 75% [32] Predisposing factors related to the syndrome: Increased airway resistance secondary to adenotonsillar hypertrophy