Face & Palate Development: Orofacial Clefts
Where the seams of the face fail to close
Facial prominences and their fates
Five swellings. The face assembles between weeks 4 and 8 around the stomodeum (primitive mouth) from five prominences whose mesenchyme comes largely from neural crest: the single frontonasal prominence and the paired maxillary and mandibular prominences of the first pharyngeal arch. Disorders of crest migration therefore produce facial clefts and jaw hypoplasia.
Nasal placodes. Ectodermal thickenings on the frontonasal prominence sink into nasal pits, each rimmed by a medial and a lateral nasal prominence. The groove between the lateral nasal and maxillary prominences becomes the nasolacrimal duct.
| Prominence | Adult structures |
|---|---|
| Frontonasal | Forehead, bridge of the nose |
| Medial nasal (merged) | Philtrum, nasal tip, premaxilla with 4 incisors, primary palate |
| Lateral nasal | Alae of the nose |
| Maxillary (1st arch) | Cheeks, lateral upper lip, maxilla, secondary palate |
| Mandibular (1st arch) | Lower lip, chin, mandible |
Building the palate
Primary palate. The two medial nasal prominences merge into the intermaxillary segment, which forms the philtrum, the premaxilla bearing the 4 maxillary incisors, and a small triangular primary palate in front of the incisive foramen.
Secondary palate. Most of the hard and all of the soft palate come from palatine shelves of the maxillary prominences.
- Shelves growFrom the maxillary prominences, hanging vertically on either side of the tongue.
- Shelves elevateAs the mandible grows and the tongue drops, the shelves swing horizontal above it.
- Midline fusionThey fuse with each other, the primary palate, and the nasal septum, front to back, between weeks 6 and 12.
The incisive foramen marks the junction of primary and secondary palates — the dividing line between cleft lip/alveolus (anterior) and cleft palate (posterior).
Orofacial clefts
| Feature | Cleft lip ± palate | Isolated cleft palate |
|---|---|---|
| Failed fusion | Maxillary prominence with merged medial nasal prominences | Palatine shelves with each other and the nasal septum |
| Position | Lateral to the philtrum, anterior to the incisive foramen, often through the alveolus; usually unilateral, left more often | Posterior to the incisive foramen |
| Sex | More common in males | More common in females (shelves fuse later) |
| Associations | Often accompanied by cleft palate | More often part of a syndrome |
Rarer clefts. Failure of the medial nasal prominences to merge gives a median cleft lip, associated with holoprosencephaly; failed maxillary–mandibular fusion widens the mouth (macrostomia); a persistent nasolacrimal groove leaves an oblique facial cleft.
Environmental risk. Maternal smoking and alcohol, antiepileptics (phenytoin, valproate, topiramate), and retinoids such as isotretinoin raise risk. Most clefts are multifactorial, so recurrence risk climbs with each affected relative.
Syndromes. Trisomy 13 pairs clefts with holoprosencephaly, polydactyly, and microphthalmia. The 22q11.2 deletion brings cleft palate, often submucous, with conotruncal heart defects, thymic hypoplasia, and hypocalcemia. Van der Woude syndrome, the classic autosomal dominant cleft syndrome (IRF6), adds pits of the lower lip.
A bifid uvula with a notched hard palate signals a submucous cleft: think 22q11 deletion and velopharyngeal insufficiency.
Pierre Robin sequence. A sequence is a cascade from one primary defect. Micrognathia displaces the tongue backward (glossoptosis); the tongue obstructs the airway and wedges between the palatine shelves, leaving a wide U-shaped cleft palate. Airway obstruction is worse supine and eased by prone positioning; Stickler syndrome, a collagen disorder most often due to COL2A1 mutations, is a frequent underlying cause.
Choanal atresia
Mechanism. Persistence of the oronasal membrane leaves the posterior nasal openings (choanae) closed. Newborns are obligate nasal breathers, so bilateral atresia causes cyanosis that worsens with feeding and resolves with crying, when the infant breathes through the mouth. Unilateral atresia is more common and may surface later as one-sided nasal discharge.
Diagnosis and care. A catheter cannot be passed through the nose; CT confirms the obstruction. Bilateral atresia needs an oral airway until surgical repair.
Choanal atresia is the "A" of CHARGE syndrome (CHD7): coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear anomalies with deafness.
Clinical consequences of cleft palate
- Feeding. An open palate prevents the negative pressure needed to suck, causing slow feeding, nasal regurgitation, and aspiration risk; special bottles and nipples help.
- Middle ear. Tensor veli palatini (CN V3) and levator veli palatini normally open the eustachian tube; their abnormal insertion leaves it closed, so otitis media with effusion and conductive hearing loss are nearly universal, often requiring tympanostomy tubes.
- Speech. Velopharyngeal insufficiency lets air escape through the nose, producing hypernasal speech.
- Teeth. Alveolar clefts often disturb the lateral incisor at the cleft site.
Tensor veli palatini is the only palatal muscle not supplied by the vagus nerve — it is a first-arch muscle innervated by V3.