Residency · Residency · Oral Maxillofacial Surgery

Embryology and Classification of Cleft Lip and Palate

Introduction

Cleft lip and palate represents the most common congenital craniofacial anomaly, affecting approximately 1 in 700 live births worldwide. Understanding the embryologic basis of cleft formation is essential for the OMFS surgeon who plays a central role in the multidisciplinary cleft team. Accurate classification guides surgical planning and prognostication.

Embryology of the Face and Palate

Facial Development (Weeks 4-8)

The face develops from five pharyngeal prominences: one frontonasal, two maxillary, and two mandibular processes. By week 4, the stomodeum (primitive mouth) is bordered by these prominences. At week 5, nasal placodes invaginate to form nasal pits, and lateral and medial nasal processes develop. During weeks 6 and 7, the medial nasal processes merge at the midline to form the intermaxillary segment, which gives rise to the primary palate, philtrum, and four incisors. At week 7, the maxillary processes fuse with the medial nasal processes; failure of this fusion results in cleft lip. The mandibular processes fuse early at the midline during week 4.

Primary Palate Formation

The primary palate is derived from the intermaxillary segment of the merged medial nasal processes. It includes the premaxilla, which contains the four upper incisors, and extends posteriorly to the incisive foramen. The incisive foramen marks the boundary between the primary and secondary palate. Clefts anterior to the incisive foramen involve the primary palate (lip and alveolus).

Secondary Palate Formation (Weeks 7-12)

Palatal shelves extend medially from the maxillary processes, initially oriented vertically and flanking the tongue. During weeks 7 and 8, the palatal shelves elevate to a horizontal position as the tongue descends. The shelves fuse in an anterior-to-posterior direction, meeting at the incisive foramen. Fusion with the nasal septum superiorly creates the separation of the oral and nasal cavities. Failure of shelf elevation, contact, or fusion results in cleft palate.

Molecular Regulation

Key signaling pathways involved include Shh (Sonic hedgehog), BMP, FGF, Wnt, and TGF-beta. Important transcription factors include MSX1, IRF6, TBX22, and PAX9, with mutations in these genes associated with clefting. Both genetic and environmental factors contribute to cleft formation through a multifactorial threshold model.

Epidemiology and Etiology

Incidence

Cleft lip with or without cleft palate (CL/P) occurs in approximately 1 in 700 births, with the highest incidence in Native American and Asian populations and lowest in those of African descent. Isolated cleft palate (CP) occurs in approximately 1 in 2,000 births and is equal across ethnic groups. CL/P is more common in males (2:1), while isolated CP is more common in females. Left-sided cleft lip is more common than right-sided (2:1).

Risk Factors

Genetic factors include family history, which increases risk 20 to 40 fold, and syndromic associations present in approximately 30% of cases. Environmental teratogens include maternal smoking, alcohol, anticonvulsants (phenytoin, valproic acid), retinoids, and folate deficiency. Folic acid supplementation (400 mcg per day) reduces the risk of neural tube defects and may reduce clefting.

Syndromic Associations

Van der Woude syndrome is the most common syndromic cause of CL/P, caused by an IRF6 mutation and characterized by lip pits. Pierre Robin sequence features micrognathia, glossoptosis, and cleft palate with potential airway compromise. Velocardiofacial (DiGeorge) syndrome involves a 22q11 deletion and presents with cleft palate, cardiac anomalies, and immune deficiency. Treacher Collins syndrome (mandibulofacial dysostosis) features cleft palate and malar hypoplasia. Stickler syndrome presents with cleft palate, myopia, and joint hypermobility due to a COL2A1 mutation.

Classification Systems

Veau Classification (1931)

Class I involves a soft palate cleft only. Class II involves a hard and soft palate cleft extending to the incisive foramen. Class III is a complete unilateral cleft lip and palate. Class IV is a complete bilateral cleft lip and palate.

Kernahan Striped-Y Classification (1971)

This is a diagrammatic representation using a Y-shaped symbol. The right and left arms represent the lip and alveolus (primary palate), while the stem represents the hard and soft palate (secondary palate). Affected segments are shaded, providing a visual shorthand for documentation.

LAHSHAL Classification

This system describes affected structures in order: Lip, Alveolus, Hard palate, Soft palate, from left to right. Capital letters indicate a complete cleft while lowercase indicates an incomplete cleft. For example, LAHshal indicates a complete left cleft of the lip, alveolus, and hard palate with an incomplete soft palate cleft.

Multidisciplinary Cleft Team

The OMFS surgeon provides alveolar bone grafting, orthognathic surgery, and distraction osteogenesis. The plastic surgeon performs primary cleft lip and palate repair. The orthodontist manages presurgical orthopedics (NAM), orthodontic alignment, and pre-surgical preparation. The speech-language pathologist assesses velopharyngeal function and provides speech therapy. The otolaryngologist manages middle ear disease and places ventilation tubes. The pediatric dentist and prosthodontist provide dental care and prosthetic rehabilitation. The geneticist performs syndrome identification and family counseling. The psychologist and social worker provide psychosocial support.

Surgical Timeline

At birth, presurgical nasoalveolar molding (NAM) is initiated if indicated. At 3 months, primary cleft lip repair is performed, following the rule of 10s (10 weeks old, 10 pounds, 10 g/dL hemoglobin). At 9 to 12 months, primary cleft palate repair is performed. At 4 to 6 years, speech assessment is conducted, with pharyngeal surgery if velopharyngeal insufficiency persists. At 7 to 9 years, alveolar bone grafting is performed during mixed dentition before canine eruption. During adolescence, definitive orthodontics and orthognathic surgery are completed if needed. In adulthood, rhinoplasty, revision surgery, and implant rehabilitation may be performed.

Clinical Pearls

The incisive foramen is the anatomic landmark dividing primary palate (lip/alveolus) from secondary palate clefts. Left-sided cleft lip is twice as common as right-sided, reflecting the slightly later fusion of the left maxillary and medial nasal processes. Approximately 30% of cleft cases are syndromic, so associated anomalies should always be evaluated. Pierre Robin sequence requires early airway assessment and management before palatal repair. Folic acid supplementation should be recommended for all women of childbearing age.

References

1. Sperber GH, Sperber SM, Guttmann GD. Craniofacial Embryogenetics and Development. 3rd ed. People's Medical Publishing House; 2018.
2. Dixon MJ, et al. "Cleft Lip and Palate: Understanding Genetic and Environmental Influences." Nature Reviews Genetics. 2011;12(3):167-178.
3. Kernahan DA. "The Striped Y -- A Symbolic Classification for Cleft Lip and Palate." Plastic and Reconstructive Surgery. 1971;47(5):469-470.
4. American Cleft Palate-Craniofacial Association. Parameters for Evaluation and Treatment of Patients with Cleft Lip/Palate or Other Craniofacial Differences. 2018.

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