Development Anomalies of Face PDF

DEVELOPMENT OF THE FACE Fevziye Figen Kaymaz M.D., Ph.D. Prof. of Histology & Embryology [email protected] 1  Objectives To learn the development of face To explain the development of palate...

DEVELOPMENT OF THE FACE Fevziye Figen Kaymaz M.D., Ph.D. Prof. of Histology & Embryology [email protected] 1  Objectives To learn the development of face To explain the development of palate 2  The facial primordia appear early in the fourth week around the stomodeum (primordium of the mouth) Facial development depends on the inductive influence of the forebrain (through sonic hedgehog morphogenic gradients), frontonasal ectodermal zone, and developing eye. 3  Five facial primordia appear as prominences around the stomodeum 1. frontonasal prominence (single) 2. maxillary prominences (paired) 3. mandibular prominences (paired) 4 The maxillary and mandibular prominences are derivatives of the first pair of pharyngeal arches. The prominences are produced mainly by the expansion of neural crest populations that originate from the mesencephalic and rostral rhombencephalic neural folds during the fourth week. These cells are the major source of connective tissue components, including cartilage, bone, and ligaments in the facial and oral regions. 5 The frontonasal prominence surrounds the ventrolateral part of the forebrain, which gives rise to the optic vesicles that form the eyes. The frontal part of the frontonasal prominence forms the forehead; the nasal part forms the rostral boundary of the stomodeum and nose. The maxillary prominences form the lateral boundaries of the stomodeum, and mandibular prominences constitute the caudal boundary of the stomodeum. The facial prominences are active centers of growth in the underlying mesenchyme. This embryonic connective tissue is continuous from one prominence to the other. 6 7  Facial development occurs mainly between the fourth and eighth weeks. By the end of the embryonic period, the face has human appearance. Facial proportions develop during the fetal period. The lower jaw and lower lip are the first parts of the face to form. They result from merging of the medial ends of the mandibular prominences in the median plane. The common chin dimple results from incomplete fusion of the prominences. 8  By the end of the fourth week, bilateral oval thickenings of the surface ectoderm (nasal placodes, the primordia of the nasal epithelium) have developed on the inferolateral parts of the frontonasal prominence. 9  These placodes are initially convex, but they are later stretched to produce a flat depression in each placode. Mesenchyme in the margins of the placodes proliferates, producing horseshoe-shaped elevations, the medial and lateral nasal prominences. As a result, the nasal placodes lie in depressions, the nasal pits. These pits are the primordia of the anterior nares (nostrils) and nasal cavities and the lateral nasal prominences form the alae (sides) of the nose. 10 11  Proliferation of mesenchyme in the maxillary prominences makes them enlarge and grow medially toward each other and the nasal prominences. This proliferation-driven expansion results in movement of the medial nasal prominences toward the median plane and each other; a process regulated by platelet-derived growth factor receptor α-polypeptide (PDGFRA) signaling. Each lateral nasal prominence is separated from the maxillary prominence by a cleft, the nasolacrimal groove 12  By the end of the fifth week, the primordia of the auricles (external part of ears) have begun to develop. Six auricular hillocks (three mesenchymal swellings on each side) form around the first pharyngeal groove, the primordia of the auricle, and the external acoustic meatus, respectively. Initially, the external ears are located in the neck region; however, as the mandible develops, they become located on the side of the head at the level of the eyes. 13 By the end of the fifth week, six auricular hillocks (mesenchymal swellings) form around the first pharyngeal groove (three on each side), the primordia of the auricle, and the external acoustic meatus (canal). 14  By the end of the sixth week, each maxillary prominence has begun to merge with the lateral nasal prominence along the line of the nasolacrimal Groove. This establishes continuity between the side of the nose, which is formed by the lateral nasal prominence, and the cheek region formed by the maxillary prominence. 15 16  The nasolacrimal duct develops from a rod-like thickening of ectoderm in the floor of the nasolacrimal groove. This thickening forms a solid epithelial cord that separates from the ectoderm and sinks into the mesenchyme. Later, as a result of apoptosis (programmed cell death), the epithelial cord canalizes to form a duct. The superior end of the duct expands to form the lacrimal sac. By the late fetal period, the nasolacrimal duct drains into the inferior meatus in the lateral wall of the nasal cavity. The duct becomes completely patent after birth. 17  Between the 7th and 10th weeks, the medial nasal prominences merge with the maxillary and lateral nasal prominences. Merging the medial nasal and maxillary prominences results in continuity of the upper jaw and lip and separation of the nasal pits from the stomodeum. As the medial nasal prominences merge, they form an intermaxillary segment. This segment forms the middle part (philtrum) of the upper lip, the premaxillary part of the maxilla and its associated gingiva (gum), and the primary palate. 18  Intermaxillary segment It is composed of (1) a labial component, which forms the philtrum ofthe upper lip; (2) an upper jaw component, which carries the four incisor teeth; (3) a palatal component, which forms the triangular primary palate The intermaxillary segment is continuous with the rostral portion of the nasal septum, which is formed by the frontal prominence. 19  Upper lip is formed from the maxillary prominences. The lower parts of the medial nasal prominences appear to have become deeply positioned and covered by medial extensions of the maxillary prominences to form the philtrum. In addition to connective tissue and muscular derivatives, various bones are derived from mesenchyme in the facial prominences. 20  Until the end of the sixth week, the primordial jaws are composed of masses of mesenchymal tissue. The lips and gingivae begin to develop when a linear thickening of the ectoderm, the labiogingival lamina, grows into the underlying mesenchyme. Gradually, most of the lamina degenerates, leaving a labiogingival groove between the lips and gingivae. A small area of the labiogingival lamina persists in the median plane to form the frenulum of the upper lip, which attaches the lip to the gum. 21  Further development of the face occurs slowly during the fetal period and results mainly from changes in the proportion and relative positions of the facial components. During the early fetal period, the nose is flat, and the mandible is underdeveloped. At 14 weeks, the nose and mandible have their characteristic form as facial development is completed. 22  Facial development requires all of the following components: The frontal nasal prominence forms the forehead and dorsum and apex of the nose The lateral nasal prominences form the alae (sides) of the nose. The medial nasal prominences form the nasal septum, ethmoid bone, and cribriform plate (openings for passage of olfactory nerves). The maxillary prominences form the upper cheek regions and lip. The mandibular prominences form the chin, lower lip, and cheek regions. 23 DEVELOPMENT OF NASAL CAVITIES As the face develops, the nasal placodes become depressed, forming nasal pits. Proliferation of the surrounding mesenchyme forms the medial and lateral nasal prominences, which results in deepening of the nasal pits and formation of primordial nasal sacs. 24  Each sac grows dorsally and ventral to the developing forebrain. At first, the sacs are separated from the oral cavity by the oronasal membrane. This membrane ruptures by the end of the sixth week, bringing the nasal and oral cavities into communication. Temporary epithelial plugs are formed in the nasal cavities from proliferation of the cells lining them. By the middle of the 16th week, the nasal plugs disappear. 25  The regions of continuity between the nasal and oral cavities are the primordial choanae (openings from the nasal cavity into the nasal pharynx). After the secondary palate develops, the choanae are located at the junction of the nasal cavity and pharynx. While these changes are occurring, the superior, middle, and inferior nasal conchae develop as elevations of the lateral walls of the nasal cavities. Concurrently, the ectodermal epithelium in the roof of each nasal cavity becomes specialized to form the olfactory epithelium. Some epithelial cells differentiate into olfactory receptor cells (neurons). The neuronal axons constitute the olfactory nerves, which grow into the olfactory bulbs of brain 26  Most of the upper lip, maxilla, and secondary palate forms from the maxillary prominences. These prominences merge laterally with the mandibular prominences. The primordial lips and cheeks are invaded by mesenchyme from the second pair of pharyngeal arches, which differentiates into the facial muscles. The muscles of facial expression are supplied by the facial nerve (CN VII), the nerve of the second arch. The mesenchyme in the first pair of arches differentiates into the muscles of mastication (chewing) and a few others, all of which are innervated by the trigeminal nerves (CN V), which supply the first pair of arches. 27  Paranasal Sinuses Some paranasal sinuses, such as maxillary sinuses, begin to develop during late fetal life; the remaining sinuses develop after birth. They form from diverticula (outgrowths) of the walls of the nasal cavities and become pneumatic (air-filled) extensions of the nasal cavities in the adjacent bones, such as the maxillary sinuses in the maxillae, and the frontal sinuses in the frontal bones. The original openings of the diverticula persist as the orifices of the adult sinuses. 28 POSTNATAL DEVELOPMENT OF PARANASAL SINUSES Most of paranasal sinuses are rudimentary or absent in neonates. The maxillary sinuses are small at birth. They grow slowly until puberty and are not fully developed until all the permanent teeth have erupted in early adulthood. No frontal or sphenoidal sinuses are present at birth. The ethmoidal cells (sinuses) are small before the age of 2 years, and they do not begin to grow rapidly until 6 to 8 years of age. 29  At approximately 2 years of age, the two most anterior ethmoidal cells grow into the frontal bone, forming a frontal sinus on each side. Usually, the frontal sinuses are visible in radiographs by the seventh year. The two most posterior ethmoidal cells grow into the sphenoid bone at approximately 2 years of age, forming two sphenoidal sinuses. Growth of the paranasal sinuses is important in altering the size and shape of the face during infancy and childhood and in adding resonance to the voice during adolescence. 30 DEVELOPMENT OF THE PALATE The palate develops from two primordia: the primary palate the secondary palate. Palatogenesis begins in the sixth week, but it is not completed until the 12th week. Molecular pathways, including WNT and PRICKLE1, are involved in this process. The critical period of palatogenesis is from the end of the sixth week until the beginning of the ninth week. 31 Primary Palate Early in the sixth week, the primary palate (median process) begins to develop. Formed by merging the medial nasal prominences, this segment is initially a wedge-shaped mass of mesenchyme between the internal surfaces of the maxillary prominences of the developing maxillae. The primary palate forms the anterior and midline aspect of the maxilla, the premaxillary part of the maxilla. It represents only a small part of the adult hard palate (anterior to the incisive fossa). 32 Secondary Palate The secondary palate is the primordium of the hard and soft parts of the palate The palate begins to develop early in the sixth week from two mesenchymal projections that extend from the internal aspects of the maxillary prominences. These lateral palatine processes (palatal shelves) initially project inferomedially on each side of the tongue. As the jaws elongate, they pull the tongue away from its root, and it is brought lower in the mouth. 33  During the seventh and eighth weeks, the lateral palatine processes assume a horizontal position above the tongue. Bone gradually develops in the primary palate, forming the premaxillary part of maxilla, which lodges the incisor teeth bone extends from the maxillae and palatine bones into the lateral palatine processes to form the hard palate. The posterior parts of these processes do not ossify. They extend posteriorly beyond the nasal septum and fuse to form the soft palate, including its soft conical projection, the uvula. The palatine raphe indicates the line of fusion of the palatine processes 34  A small nasopalatine canal persists in the median plane of the palate between the anterior part of the maxilla and the palatine processes of the maxillae. This canal is represented in the adult hard palate by the incisive fossa, which is the common opening for the small right and left incisive canals. An irregular suture runs on each side from the fossa to the alveolar process of the maxilla between the lateral incisor and canine teeth on each side. It is visible in the anterior region of the palates of young persons. This suture indicates where the embryonic primary and secondary palates fused.35  The nasal septum develops as a down growth from internal parts of the merged medial nasal prominences. The fusion between the nasal septum and palatine processes begins anteriorly during the ninth week, and it is completed posteriorly by the 12th week superior to the primordium of the hard palate 36  TEETH The shape of the face is determined not only by expansion of the paranasal sinuses but also by growth of the mandible and maxilla to accommodate the teeth. Teeth themselves arise from an epithelial— mesenchymal interaction between overlying oral epithelium and underlying mesenchyme derived from neural crest cells. By the sixth week of development, the basal layer of the epithelial lining of the oral cavity forms a C-shaped structure, the dental lamina, along the length of the upper and lower jaws. This lamina subsequently gives rise to a number of dental buds 37  10 in each jaw, which form the primordia of the ectodermal components of the teeth. Soon, the deep surface of the buds invaginates, resulting in the cap stage of tooth development Such a cap consists of an outer layer, the outer dental epithelium; an inner layer, the inner dental epithelium; and a central core of loosely woven tissue, the stellate reticulum. The mesenchyme, which originates in the neural crest in the indentation, forms the dental papilla 38  As the dental cap grows and the indentation deepens, the tooth takes on the appearance of a bell (bell stage). Mesenchyme cells of the papilla adjacent to the inner dental layer differentiate into odontoblasts, which later produce dentin. With thickening of the dentin layer, odontoblasts retreat into the dental papilla, leaving a thin cytoplasmic process (dental process) behind in the dentin The odontoblast layer persists throughout the life of the tooth and continuously provides predentin. The remaining cells of the dental papilla form the pulp of the tooth 39  In the meantime, epithelial cells of the inner dental epithelium differentiate into ameloblasts (enamel formers). These cells produce long enamel prisms that are deposited over the dentin. Furthermore, a cluster of these cells in the inner dental epithelium forms the enamel knot that regulates early tooth development. 40  Enamel is first laid down at the apex of the tooth and from here spreads toward the neck. When the enamel thickens, the ameloblasts retreat into the stellate reticulum. Here they regress, temporarily leaving a thin membrane (dental cuticle) on the surface of the enamel. After eruption of the tooth, this membrane gradually sloughs off 41  Formation of the root of the tooth begins when the dental epithelial layers penetrate into the underlying mesenchyme and form the epithelial root sheath. 42  Cells of the dental papilla lay down a layer of dentin continuous with that of the crown. As more and more dentin is deposited, the pulp chamber narrows and finally forms a canal containing blood vessels and nerves of the tooth. 43  Mesenchymal cells on the outside of the tooth and in contact with dentin of the root differentiate into cementoblasts. These cells produce a thin layer of specialized bone, the cementum. Outside of the cement layer, mesenchyme gives rise to the periodontal ligament, which holds the tooth firmly in position and functions as a shock absorber. 44  With further lengthening of the root, the crown is gradually pushed through the overlying tissue layers into the oral cavity. The eruption of deciduous or milk teeth occurs 6 to 24 months after birth. 45  Buds for the permanent teeth, which lie on the lingual aspect of the milk teeth, are formed during the third month of development. These buds remain dormant until approximately the sixth year of postnatal life. Then they begin to grow, pushing against the underside of the milk teeth and aiding in the shedding of them. As a permanent tooth grows, the root of the overlying deciduous tooth is resorbed by osteoclasts. 46 Anomalies of Face Development Fevziye Figen Kaymaz M.D., Ph.D. Prof. of Histology & Embryology [email protected] 47 OBJECTIVES To learn the developmental anomalies of face To identify the types of cleft lip and palate 48  ATRESIA OF THE NASOLACRIMAL DUCT Part of the nasolacrimal duct occasionally fails to canalize, resulting in congenital atresia (lack of an opening) of the nasolacrimal duct. Obstruction of this duct with clinical symptoms occurs in approximately 6% of neonates. CONGENITAL AURICULAR SINUSES AND CYSTS Small auricular sinuses and cysts are usually located in a triangular area of skin anterior to the auricle of the external ear however, they may occur in other sites around the auricle or in the lobule (earlobe). Although some sinuses and cysts are remnants of the first pharyngeal groove, others represent ectodermal folds sequestered during formation of the auricle from six auricular hillocks (nodular masses of mesenchyme from the first and second arches that coalesce to form the auricle). The sinuses and cysts are classified as minor defects that have no serious medical consequences. 50 Auricular Sinus & Cysts Remnants of 1st branchial cleft Located at triangular skin region anterior to auricle Little anomalies that not causes clinical importance CLEFT LIP AND CLEFT PALATE Clefts of the upper lip and palate are common craniofacial birth defects. they result in an abnormal facial appearance and defective speech. There are two major groups of cleft lip and cleft palate: -Anterior cleft defects -Posterior cleft defects  Anterior cleft defects include cleft lip with or without a cleft of the alveolar part of the maxilla. In a complete anterior cleft defect, the cleft extends through the upper lip and alveolar part of the maxilla to the incisive fossa, separating the anterior and posterior parts of the palate Anterior cleft defects result from a deficiency of mesenchyme in the maxillary prominences and the median palatine process.  Posterior cleft defects include clefts of the secondary palate that extend through the soft and hard regions of the palate to the incisive fossa, separating the anterior and posterior parts of the palate Posterior cleft defects result from defective development of the secondary palate and growth distortions of the lateral palatine processes that prevent their fusion. Other factors such as the width of the stomodeum, mobility of the lateral palatine processes (palatal shelves), and altered focal degeneration sites of the palatal epithelium may contribute to these birth defects.  A cleft lip with or without a cleft palate occurs approximately once in 1000 births, Between 60% and 80% of affected neonates are male. The clefts vary from incomplete cleft lip to those that extend into the nose and through the alveolar part of the maxilla Cleft lip may be unilateral or bilateral.  A unilateral cleft lip results from failure of the maxillary prominence on the affected side to unite with the merged medial nasal prominences. Failure of the mesenchymal masses to merge and mesenchyme to proliferate and smooth the overlying epithelium results in a persistent labia Groove. The epithelium in the labial groove becomes stretched, and the tissue in the floor of the groove breaks down, resulting in a lip that is divided into medial and lateral parts. A bridge of tissue, called the Simonart band, sometimes joins the parts of the incomplete unilateral cleft lip.  A bilateral cleft lip results from failure of the mesenchymal masses in both maxillary prominences to meet and unite with the merged medial nasal prominences. The epithelium in both labial grooves becomes stretched and breaks. In bilateral cases, the defects may be dissimilar, with various degrees of defect on each side. When there is a complete bilateral cleft of lip and alveolar part of the maxilla, the median palatal process hangs free and projects anteriorly. These defects are especially deforming because of the loss of continuity of the orbicularis oris muscle, which closes the mouth and purses the lips.  A median cleft lip is a rare defect that results from a mesenchymal deficiency. This defect causes partial or complete failure of the medial nasal prominences to merge and form the median palatal process. A median cleft of the lower lip is also rare and results from failure of the mesenchymal masses in the mandibular prominences to merge completely and smooth the embryonic cleft between them.  A cleft palate with or without a cleft lip occurs approximately once in 2500 births, and it is more common in girls than in boys. The cleft may involve only the uvula or the cleft may extend through the soft and hard regions of the palate. In severe cases associated with a cleft lip, the cleft in the palate extends through the alveolar part of the maxilla and lips on both sides A complete cleft palate is the maximum degree of clefting of any particular type. For example, a complete cleft of the posterior palate is a defect in which the cleft extends through the soft palate and anteriorly to the incisive fossa The landmark for distinguishing anterior from posterior cleft defects is the incisive fossa. Unilateral and bilateral clefts of the palate are classified in three groups:  Clefts of the anterior palate (clefts anterior to the incisive fossa) result from failure of mesenchymal masses in the lateral palatal processes to meet and fuse with the mesenchyme in the primary palate.  Clefts of the posterior palate (clefts posterior to the incisive fossa) result from failure of mesenchymal masses in the lateral palatine processes to meet and fuse with each other and the nasal septum.  Clefts of the secondary parts of the palate (clefts of the anterior and posterior palates) result from failure of the mesenchymal masses in the lateral palatine processes to meet and fuse with mesenchyme in the primary palate, with each other, and the nasal septum. Cleft Lip and Cleft Palate Infant with unilateral cleft lip and cleft palate. Clefts of the lip, with or without a cleft palate, occur in approximately 1 in 1000 births; most affected individuals are boys. (Courtesy of A.E. Chudley, MD, Professor of Pediatrics and Child Health, Children's Hospital and University of Manitoba, Winnipeg, Manitoba, Canada.)  Most clefts of the upper lip and palate result from multiple genetic and nongenetic factors (multifactorial inheritance; with each causing a minor developmental disturbance. Several studies show that the interferon regulatory factor 6 gene (IRF6) is involved in the formation of isolated clefts.  Some clefts of the lip and/or palate appear as part of syndromes determined by single mutant genes. Other clefts are parts of chromosomal syndromes, especially trisomy 13. A few cases of cleft lip and/or palate appear to have been caused by teratogenic agents (e.g., anticonvulsant drugs). Studies of twins indicate that genetic factors are more important in cases of cleft lip with or without a cleft palate than in cleft palate alone.  A sibling of a child with a cleft palate has an elevated risk of cleft palate but has no increased risk of cleft lip. A cleft of the lip and alveolar process of the maxilla that continues through the palate is usually transmitted through a male sex-linked gene. When neither parent is affected, the recurrence risk in subsequent siblings is approximately 4%. OTHER FACIAL DEFECTS Congenital microstomia (small mouth) results from excessive merging of the mesenchymal masses in the maxillary and mandibular prominences of the first pharyngeal arch. In severe cases, the defect may be associated with underdevelopment (hypoplasia) of the mandible. A single nostril results when only one nasal placode forms. A bifid nose results when the medial nasal prominences do not merge completely; the nostrils are widely separated and the nasal bridge is bifid. In mild forms, there is a groove in the tip of the nose. At the beginning of the second trimester, features of the fetal face can be identified sonographically. Using this imaging technique, facial defects such as a cleft lip are readily recognizable.  Various types of facial clefts occur, but all FACIAL CLEFTS are rare. Severe clefts are usually associated with gross defects of the head. Oblique facial clefts are often bilateral and extend from the upper lip to the medial margin of the orbita. When this occurs, the nasolacrimal ducts are open grooves (persistent nasolacrimal grooves). Oblique facial clefts associated with cleft lip result from failure of the mesenchymal masses in the maxillary prominences to merge with the lateral and medial nasal prominences. Lateral or transverse facial clefts run from the mouth toward the ear. Bilateral clefts result in a very large mouth (macrostomia). In severe cases, the clefts in the cheeks extend almost to ears Tooth Abnormalities Natal teeth have erupted by the time of birth. Usually, they involve the mandibular incisors, which may be abnormally formed and have little enamel. Teeth may be abnormal in number, shape, and size. They may be discolored by foreign substances, such as tetracyclines, or be deficient in enamel, a condition often caused by vitamin D deficiency [rickets]. Many factors affect tooth development, including genetic and environmental influences.  References 1. Sadler TW, Langman's Medical Embryology 13E 2. Moore KL, Persaud TVN, Torchia MG Developing Human 9e 3. Carlson BM Human Embryology & Developmental Biology, 5E 71