Development of the Face fundamental aspects of normal facial development common developmental deformities Photographs of human embryos from the Kyoto Collection at Carnegie stages 16 (ca. 39 days), 17 (ca. 41 days), and 18 (ca. 44 days), illustrating three stages of early facial development.

Development of the Face (Facial Prominences—Middle of 4th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—End of 4th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—Middle of 5th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—Middle of 5th Week) ~ 33 days (SEM in Anterolateral View) From Moore & Persaud (2003)

Development of the Face (Facial Prominences—Middle of 5th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—End of 5th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—Middle of 6th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—End of 6th Week) ~ 41 days (SEM in Oblique Right Anterolateral View) From Moore & Persaud (2003)

Development of the Face (Facial Prominences—Process of Fusion) epithelium ectomesenchyme Modified from Jugessur et al. (2009)

Development of the Face (Facial Prominences—End of 7th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—End of 7th Week) plane of section in following slides (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Adapted from Moore & Persaud (2003) Development of the Face (Formation of the Intermaxillary Segment—Weeks 6–10) (Schematic Horizontal Sections) Adapted from Moore & Persaud (2003)

Adapted from Moore & Persaud (2003) Development of the Face (Formation of the Intermaxillary Segment—Weeks 6–10) (Schematic Horizontal Sections) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—10th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—14th Week) (Anterior View) (Lateral View) Adapted from Moore & Persaud (2003)

Development of the Face (Facial Prominences—Contributions to External Soft Tissues of the Face) Lateral Nasal Prominences lateral part of nose (alae) Frontonasal Prominence forehead bridge of nose Maxillary Prominences lateral portions of upper lip upper portions of cheeks Medial Nasal Prominences central portion of upper lip (philtrum) crest and tip of nose Mandibular Prominences lower lip lower portions of cheeks Modified from Standring (2008)

Modified from Moore & Persaud (2003) Development of the Nasal Apparatus (Formation of the Nasal Cavities and Choanae) ≈ 5 weeks ≈ 6 weeks (Schematic Median Sagittal Sections) [nasal septum omitted] Modified from Moore & Persaud (2003)

(Schematic Median Sagittal Sections) [nasal septum omitted] Development of the Nasal Apparatus (Formation of the Nasal Cavities and Choanae) ≈ 7 weeks ≈ 12 weeks (Schematic Median Sagittal Sections) [nasal septum omitted] Modified from Moore & Persaud (2003)

Modified from Sadler (2006) Development of the Palate (Primary [Anterior] Palate—Intermaxillary Segment) (Schematic Horizontal Section) [embryo] (Schematic Palatal View) [child] Modified from Sadler (2006)

Adapted from Moore & Persaud (2003) Development of the Palate (Secondary [Posterior] Palate—Lateral Palatine Processes) ≈ early 8th week (Schematic Coronal Section) (Schematic Palatal View) Adapted from Moore & Persaud (2003)

Adapted from Moore & Persaud (2003) Development of the Palate (Secondary [Posterior] Palate—Lateral Palatine Processes) ≈ late 8th week (Schematic Coronal Section) (Schematic Palatal View) Adapted from Moore & Persaud (2003)

Adapted from Moore & Persaud (2003) Development of the Palate (Secondary [Posterior] Palate—Lateral Palatine Processes) ≈ 12th week (Schematic Coronal Section) (Schematic Palatal View) Adapted from Moore & Persaud (2003)

Development of the Face, Palate, and Nose (Facial Prominences—Summary of Key Soft and Hard Tissue Derivatives) Lateral Nasal Prominences lateral part of nose (alae) Frontonasal Prominence forehead bridge of nose cartilaginous nasal septum (part) frontals, nasals, lacrimals Maxillary Prominences lateral portions of upper lip upper portions of cheeks secondary palate maxillae (except premaxillary parts) palatines, vomers, intramembranous portions of sphenoid, zygomatic bones, squamous portions of temporal bones Medial Nasal Prominences central portion of upper lip (philtrum) crest and tip of nose premaxillary portion of maxillary alveolar process primary palate cartilaginous nasal septum (part) Mandibular Prominences lower lip lower portions of cheeks mandible incudes and mallei (ear ossicles) Modified from Standring (2008)

Orofacial Clefts (General Categories of Cleft Deformities) From Tessier (1976)

Normal (No Cleft Deformities) Orofacial Clefts (General Categories of Cleft Deformities—Anterior vs. Posterior Clefts) Normal (No Cleft Deformities) nostril upper lip alveolar process of maxilla primary palate incisive fossa secondary palate (Schematic Palatal Views) uvula Anterior + Posterior Cleft Deformities (=“cleft lip-cleft palate” [CLP]) Anterior Cleft Deformity (≈ “cleft lip” [CL]) Posterior Cleft Deformity (≈ “cleft palate” [CP]) Adapted from Sadler (2006)

Orofacial Clefts (General Categories of Cleft Deformities—Typical vs Orofacial Clefts (General Categories of Cleft Deformities—Typical vs. Atypical Clefts) Cleft lip (CL), cleft palate (CP), and cleft lip-cleft palate (CLP) collectively account for approximately 80% or more of all orofacial cleft deformities, and are therefore referred to as “typical” cleft deformities. Other orofacial cleft deformities (e.g., median clefts of the upper and lower lips, oblique facial clefts, transverse facial clefts) are far less common, and are therefore referred to as “atypical” cleft deformities.

Orofacial Clefts (Typical Cleft Deformities—Underlying Causes and Functional Effects) Most cases result from multiple factors, both genetic and nongenetic Among genetic factors, CL, CLP, and CP are collectively known to be associated with an ever-growing list of 500+ Mendelian syndromes; consequently, cases are generally categorized as being either syndromic or nonsyndromic (isolated) ≈70% of all cases of CL ± P and ≈50% of all cases of CP are isolated Among nongenetic factors, maternal smoking, alcohol consumption, use of corticosteroids and some anticonvulsants, folic acid deficiency, and high altitude are all known to increase the risk of CL, CLP, and CP CL, CLP, and CP can impair feeding (including suckling), drinking, speech, respiration, and ear function—not to mention socialization

Orofacial Clefts (Typical Cleft Deformities—Prevalence) Among typical cleft deformities, CLP accounts for ≈50% of all cases, CP accounts for ≈30% of all cases, and CL accounts for ≈20% of all cases Prevalences of CL, CLP, and CP vary among populations; in general, Asian-derived populations > European-derived populations > African- derived populations Overall prevalence of CL ± P: ≈1/1000 births (♂:♀ ≈ 2:1) Overall prevalence of CP: ≈1/2500 births (♂:♀ ≈ 1:2) In cases of unilateral CL ± P, L:R ≈ 2:1 Bilateral clefts of the lip are more frequently associated with clefts of the palate (≈86%) than are unilateral clefts of the lip (≈68%)

Orofacial Clefts (Typical Cleft Deformities—Cleft Palate [CP]) nostril upper lip alveolar process of maxilla primary palate incisive fossa (Schematic Palatal View) secondary palate uvula failure (complete or incomplete) of lateral palatine processes to merge together at the midline Adapted from Sadler (2006)

Orofacial Clefts (Typical Cleft Deformities—Cleft Palate [CP]) Cleft Uvula (Incomplete) Cleft Soft Palate (Complete) Cleft Soft + Hard Palate (Incomplete) Cleft Soft + Hard Palate (Complete) Modified from Silva Filho et al. (2007)

Orofacial Clefts (Typical Cleft Deformities—Cleft Palate [CP]) Unilateral Bilateral Modified from Moore & Persaud (2003) and Silva Filho et al. (2007)

Orofacial Clefts (Typical Cleft Deformities—Unilateral Cleft Lip [CL]) failure (complete or incomplete) of ipsilateral maxillary and medial nasal prominences to merge together Modified from Standring (2008) Modified from Dixon (2011)

Orofacial Clefts (Typical Cleft Deformities—Unilateral Cleft Lip [CL]) Incomplete Complete Modified from Koh et al. (2008) Modified from Cho (2006)

Orofacial Clefts (Typical Cleft Deformities—Bilateral Cleft Lip [CL]) failure (complete or incomplete) of maxillary and medial nasal prominences to merge together on both sides Incomplete Modified from Standring (2008) Modified from Dixon (2011) and Eppley et al. (2005)

Orofacial Clefts (Typical Cleft Deformities—Bilateral Cleft Lip [CL]) failure (complete or incomplete) of maxillary and medial nasal prominences to merge together on both sides Complete Modified from Standring (2008) Modified from Dixon (2011)

Adapted from Dixon (2011) and Sliva Filho et al. (2006) Orofacial Clefts (Typical Cleft Deformities—Cleft Lip-Cleft Palate [CLP]) Unilateral Bilateral Simonart’s Band Adapted from Dixon (2011) and Sliva Filho et al. (2006)

Orofacial Clefts (Atypical Cleft Deformities) From Tessier (1976)

Adapted from Tessier (1976) Orofacial Clefts (Atypical Cleft Deformities—Oblique Facial Clefts [Unilateral]) failure (complete or incomplete) of maxillary prominence to merge together with ipsilateral medial and lateral nasal prominences Modified from Standring (2008) Adapted from Tessier (1976)

Orofacial Clefts (Atypical Cleft Deformities—Oblique Facial Clefts [Bilateral]) failure (complete or incomplete) of maxillary prominence to merge together with ipsilateral medial and lateral nasal prominences on both left and right sides Modified from Standring (2008) Adapted from Tessier (1976)

Orofacial Clefts (Atypical Cleft Deformities—Transverse Facial Clefts) Bilateral Macrostomia From Gleizal et al. (2007)

Orofacial Clefts (Atypical Cleft Deformities—Median Cleft Lip) failure (complete or incomplete) of medial nasal prominences to merge together at the midline Modified from Standring (2008) Modified from Eppley et al. (2005) and Muenke (2002)

Orofacial Clefts (Atypical Cleft Deformities—Median Cleft Lower Lip) failure (complete or incomplete) of mandibular prominences to merge together at the midline Modified from Standring (2008) Modified from Eppley et al. (2005) and Ishii et al. (2002)