Pharyngeal Apparatus, Face, and Neck





T he pharyngeal apparatus consists of pharyngeal arches, pouches, grooves, and membranes ( Fig. 9.1 ). These early embryonic structures contribute to the formation of the face and neck.




Fig. 9.1


Pharyngeal apparatus. A , Dorsal view of the upper part of a 23-day embryo. B to D , Lateral views show later development of the pharyngeal arches. E to G , Ventral or facial views show the relationship of the first arch to the stomodeum. H , Horizontal section through the cranial region of an embryo. I , Similar section shows the arch components and floor of the primordial pharynx. J , Sagittal section of the cranial region of an embryo shows the openings of the pouches in the lateral wall of the primordial pharynx.


Pharyngeal Arches


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The pharyngeal arches begin to develop early in the fourth week as neural crest cells migrate into the future head and neck regions (see Chapter 5 , Fig. 5.5 ). The first pair of arches, the primordial jaws, appears as surface elevations lateral to the developing pharynx (see Fig. 9.1 A and B ). Other arches soon appear as ridges on each side of the future head and neck regions (see Fig. 9.1 C and D ). By the end of the fourth week, four pairs of arches are visible externally (see Fig. 9.1 D ). The fifth and sixth arches are rudimentary and are not visible on the surface of the embryo. Sonic hedgehog (Shh) and homeobox gene Dlx2 signaling play an important role in the formation and patterning (anterior-posterior and dorsoventral) of the pharyngeal arches.


The pharyngeal arches are separated by pharyngeal grooves (clefts). Like the arches, the grooves are numbered in a craniocaudal sequence (see Fig. 9.1 D ). The first arch separates into the maxillary and mandibular prominences ( Fig. 9.2 ; see Fig. 9.1 E ). The maxillary prominence forms the maxilla, zygomatic bone, and a portion of the vomer bone. The mandibular prominence forms the mandible and squamous temporal bone. Along with the third arch, the second arch (hyoid arch) contributes to the formation of the hyoid bone.




Fig. 9.2


Photograph of a stage 13, 4.5-week human embryo.

(Courtesy the late Professor Emeritus Dr. K. V. Hinrichsen, Medizinische Fakultät, Institut für Anatomie, Ruhr-Universität Bochum, Bochum, Germany.)


The arches support the lateral walls of the primordial pharynx , which is derived from the cranial part of the foregut. The stomodeum (primordial mouth) initially appears as a slight depression of the surface ectoderm (see Fig. 9.1 D and G ). It is separated from the cavity of the primordial pharynx by a bilaminar membrane, the oropharyngeal membrane , which is composed of ectoderm externally and endoderm internally (see Fig. 9.1 E and F ). This membrane ruptures at approximately 26 days, bringing the pharynx and foregut in communication with the amniotic cavity. Persistence of the oropharyngeal membrane may result in orofacial defects. The ectodermal lining of the first arch forms the oral epithelium.


Pharyngeal Arch Components


Each arch consists of a core of mesenchyme (embryonic connective tissue) and is covered externally by ectoderm and internally by endoderm (see Fig. 9.1 H and I ). Originally, the mesenchyme is derived during the third week from mesoderm. During the fourth week, most of the mesenchyme is derived from neural crest cells that migrate into the arches. Migration of the multipotent neural crest stem cells into the arches and their differentiation into mesenchyme produce the maxillary and mandibular prominences (see Fig. 9.2 ) in addition to all connective tissue, including the dermis (layer of skin) and smooth muscle.


Coincident with the immigration of neural crest cells, myogenic mesoderm from paraxial regions moves into each arch, forming a central core of muscle primordium . Endothelial cells in the arches are derived from the lateral mesoderm and invasive angioblasts (cells that differentiate into blood vessel endothelium) that move into the arches. The endothelium of the pharyngeal arches 3 to 6 is derived from endothelial progenitors of the second heart field. The pharyngeal endoderm plays an essential role in regulating the development of the arches.


A typical pharyngeal arch contains several structures:




  • An artery arises from the truncus arteriosus of the primordial heart ( Fig. 9.3 B ) and passes around the primordial pharynx to enter the dorsal aorta.




    Fig. 9.3


    A , Drawing of the head, neck, and thoracic regions of an embryo at approximately 28 days’ gestation shows the pharyngeal apparatus. Inset, Photograph of an embryo of approximately the same age as shown in A . B , Schematic drawing shows the pouches and arch arteries. C , Horizontal section through the embryo shows the floor of the primordial pharynx and the germ layer of origin of the arch components.

    ( Inset , Courtesy Dr. Bradley R. Smith, University of Michigan, Ann Arbor, MI.)



  • A cartilaginous rod forms the skeleton of the arch.



  • A muscular component differentiates into muscles in the head and neck.



  • Sensory and motor nerves supply the mucosa (tissue lining) and muscles derived from each arch. The nerves that grow into the arches are derived from neuroectoderm of the primordial brain.



Fate of Pharyngeal Arches


The arches contribute extensively to the formation of the face, nasal cavities, mouth, larynx, pharynx, and neck (see Figs. 9.3 and 9.25 ). During the fifth week, the second arch enlarges and overgrows the third and fourth arches, forming an ectodermal depression, the cervical sinus (see Figs. 9.2 and 9.7 ). By the end of the seventh week, the second to fourth grooves and cervical sinus have disappeared, giving the neck a smooth contour.


Derivatives of Pharyngeal Arch Cartilages


The dorsal end of the first arch cartilage (Meckel cartilage) is closely related to the developing ear. Early in development, small nodules break away from the proximal part of the cartilage and form two of the middle ear bones, the malleus and incus ( Fig. 9.4 and Table 9.1 ). The middle part of the cartilage regresses, but its perichondrium (connective tissue membrane around cartilage) forms the anterior ligament of malleus and sphenomandibular ligament .




Fig. 9.4


A , Schematic lateral view of the head, neck, and thoracic regions of a 4-week embryo shows the location of the cartilages in the pharyngeal arches. B , Similar view of a 24-week fetus shows the derivatives of the arch cartilages. The mandible is formed by intramembranous ossification of mesenchymal tissue surrounding the first arch cartilage. The cartilage acts as a template for development of the mandible but does not contribute directly to its formation. Occasionally, ossification of the second arch cartilage may extend from the styloid process along the stylohyoid ligament. When this occurs, it may cause pain in the region of the palatine tonsil.


Table 9.1

Structures Derived From Pharyngeal Arch Components


































Arches * Cranial Nerves Muscles Skeletal Structures Ligaments
First (mandibular) Trigeminal (CN V) Muscles of mastication
Mylohyoid and anterior belly of digastric
Tensor tympani
Tensor veli palatini
Malleus
Incus
Anterior ligament of malleus
Sphenomandibular ligament
Second (hyoid) Facial (CN VII) Muscles of facial expression §
Stapedius
Stylohyoid
Posterior belly of digastric
Stapes
Styloid process
Upper part of body and lesser cornu of hyoid bone
Stylohyoid ligament
Third Glossopharyngeal (CN IX) Stylopharyngeus Lower part of body and greater cornu of hyoid bone
Superior cornu of the thyroid cartilage
Fourth and sixth Superior laryngeal branch of vagus (CN X)
Recurrent laryngeal branch of vagus (CN X)
Cricothyroid
Levator veli palatini
Constrictors of pharynx
Intrinsic muscles of larynx
Striated muscles of esophagus
Thyroid cartilage
Cricoid cartilage
Arytenoid cartilage
Corniculate cartilage
Cuneiform cartilage
Body of Hyoid Bone

* The derivatives of the pharyngeal arch arteries are described in Fig. 13.38 in Chapter 13 .


The ophthalmic division of the fifth cranial nerve (CN V) does not supply any pharyngeal arch components.


Temporalis, masseter, medial, and lateral pterygoids.


§ Buccinator, auricularis, frontalis, platysma, orbicularis oris, and orbicularis oculi.


The fifth pharyngeal arch is often absent. When present, it is rudimentary and usually has no recognizable cartilage bar. The cartilaginous components of the fourth and sixth arches fuse to form the cartilages of the larynx.



Ventral parts of the first arch cartilages form the horseshoe-shaped primordium of the mandible , and by keeping pace with its growth, they guide its early morphogenesis. Each half of the mandible forms lateral to and in close association with its cartilage. The first arch cartilage disappears as the mandible develops around it by intramembranous ossification (see Fig. 9.4 B ). Multiple signaling pathways involving the expression of homeobox genes ( BMP, PRRX1, and PRRX2 ), and fibroblast growth factors regulate the morphogenesis of the mandible.


An independent cartilage, the anlage (primordium) near the dorsal end of the second arch cartilage (Reichert cartilage), participates in ear development. It contributes to the formation of the stapes of the middle ear and the styloid process of the temporal bone (see Fig. 9.4 B ). The cartilage between the styloid process and hyoid bone regresses; its perichondrium forms the stylohyoid ligament . The ventral end of the second arch cartilage ossifies to form the hyoid lesser cornu (lesser horn; see Fig. 9.4 B ).


The third arch cartilage , located in the ventral part of the arch, ossifies to form the greater cornu of the hyoid bone and the superior cornu of the thyroid cartilage. The body of the hyoid bone is formed by the hypobranchial eminence (see Fig. 9.23 ).


The fourth and sixth arch cartilages fuse to form the laryngeal cartilages (see Fig. 9.4 B and Table 9.1 ), except for the epiglottis. The cartilage of the epiglottis develops from mesenchyme in the hypopharyngeal eminence (see Fig. 9.23 A ), a prominence in the floor of the embryonic pharynx that is derived from the third and fourth arches. The fifth arch , if present, is rudimentary and has no derivatives.


Derivatives of Pharyngeal Arch Muscles


The muscular components of the arches derived from unsegmented paraxial mesoderm and prechordal plate form various muscles in the head and neck. The musculature of the first arch forms the muscles of mastication and other muscles ( Fig. 9.5 ; see Table 9.1 ). The musculature of the second arch forms the stapedius , stylohyoid, posterior belly of digastric, auricular, and muscles of facial expression . The musculature of the third arch forms the stylopharyngeus . The musculature of the fourth arch forms the cricothyroid , levator veli palatini , and constrictors of pharynx . The musculature of the sixth arch forms the intrinsic muscles of the larynx.




Fig. 9.5


A , Lateral view of the head, neck, and thoracic regions of a 4-week embryo shows the muscles derived from the pharyngeal arches. The arrow shows the pathway taken by myoblasts from the occipital myotomes to form the tongue musculature. B , Sketch of the dissected head and neck regions of a 20-week fetus shows the muscles derived from the arches. Parts of the platysma and sternocleidomastoid muscles have been removed to show the deeper muscles. The myoblasts from the second arch migrate from the neck to the head, where they give rise to the muscles of facial expression. These muscles are supplied by the facial nerve (cranial nerve VII), which is the nerve of the second arch.


Derivatives of Pharyngeal Arch Nerves


Each arch is supplied by its own cranial nerve (CN). The special visceral efferent (branchial) components of these nerves supply muscles derived from the arches ( Fig. 9.6 , see Table 9.1 ). Because mesenchyme from the arches contributes to the dermis and mucous membranes of the head and neck, these areas are supplied with special visceral afferent nerves.




Fig. 9.6


A , Lateral view of the head, neck, and thoracic regions of a 4-week embryo shows the cranial nerves supplying the pharyngeal arches. B , Sketch of the head and neck regions of a 20-week fetus shows the superficial distribution of the two caudal branches of the first arch nerve (cranial nerve V). C , Sagittal section of the fetal head and neck shows the deep distribution of sensory fibers of the nerves to the teeth and mucosa of the tongue, pharynx, nasal cavity, palate, and larynx.


The facial skin is supplied by the trigeminal nerve (CN V); however, only its caudal two branches (maxillary and mandibular) supply derivatives of the first arch (see Fig. 9.6 B ). CN V is the principal sensory nerve of the head and neck and is the motor nerve for the muscles of mastication (see Table 9.1 ). Its sensory branches innervate the face, teeth, and mucous membranes of nasal cavities, palate, mouth, and tongue (see Fig. 9.6 C ).


The facial nerve (CN VII), glossopharyngeal nerve (CN IX), and vagus nerve (CN X) supply the second, third, and fourth to sixth (caudal) arches, respectively. The fourth arch is supplied by the superior laryngeal branch of CN X and by its recurrent laryngeal branch. The nerves of the second to sixth arches have little cutaneous distribution (see Fig. 9.6 C ), but they innervate the mucous membranes of the tongue, pharynx, and larynx.




Pharyngeal Pouches


The primordial pharynx , which is derived from the foregut, widens cranially as it joins the stomodeum (see Figs. 9.3 A and B and 9.4 B ) and narrows as it joins the esophagus. The endoderm of the pharynx lines the internal aspects of the arches and the pharyngeal pouches (see Figs. 9.1 H to J and 9.3 B and C ). The pouches develop as outpocketing of the endoderm in a craniocaudal sequence between the arches. The first pair of pouches, for example, lies between the first and second arches. Four pairs of pouches are well defined; the fifth pair (if present) is rudimentary. The endoderm of the pouches contacts the ectoderm of the pharyngeal grooves, and they form the double-layered pharyngeal membranes that separate the pouches from the grooves (see Figs. 9.1 H and 9.3 C ). Retinoic acid, Wnt, and fibroblast growth factor (Fgf) signaling play an essential role in the formation and differentiation of the pharyngeal pouches.


Derivatives of Pharyngeal Pouches


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The endodermal epithelial lining of the pouches forms important organs in the head and neck.


First Pharyngeal Pouch


The first pouch expands into an elongated tubotympanic recess ( Fig. 9.7 B ). The expanded distal part of this recess contacts the first groove, where it later contributes to the formation of the tympanic membrane (eardrum). The cavity of the tubotympanic recess becomes the tympanic cavity and mastoid antrum . The connection of the tubotympanic recess with the pharynx gradually elongates to form the pharyngotympanic tube (auditory tube).




Fig. 9.7


Schematic horizontal sections at the level shown in Fig. 9.5 A illustrate the adult derivatives of the pharyngeal pouches. A , At 5 weeks, the second arch grows over the third and fourth arches, burying the second to fourth grooves in the cervical sinus. B , Development at 6 weeks. C , At 7 weeks, the developing thymus, parathyroid, and thyroid glands migrate into the neck (arrows) .


Second Pharyngeal Pouch


Although the second pouch is largely obliterated as the palatine tonsil develops, part of the cavity of this pouch remains as the tonsillar sinus (fossa), the depression between the palatoglossal and palatopharyngeal arches ( Fig. 9.8 ; see Fig. 9.7 C ). The endoderm of the second pouch proliferates and grows into the underlying mesenchyme. The central parts of these buds break down, forming tonsillar crypts (pit-like depressions). The pouch endoderm forms the surface epithelium and lining of the tonsillar crypts. At approximately 20 weeks, the mesenchyme around the crypts differentiates into lymphoid tissue , which soon organizes into the lymphatic nodules of the palatine tonsil (see Fig. 9.7 C ). Initial lymphoid cell infiltration occurs at approximately the seventh month, with germinal centers forming in the neonatal period and active germinal centers within the first year of life.




Fig. 9.8


Schematic sagittal section of the head, neck, and upper thoracic regions of a 20-week fetus shows the adult derivatives of the pharyngeal pouches and the descent of the thyroid gland into the neck (broken line) .


Third Pharyngeal Pouch


The third pouch expands and forms a solid, dorsal, bulbar part and a hollow, elongated, ventral part (see Fig. 9.7 B ). Its connection with the pharynx is reduced to a narrow duct that soon degenerates. By the sixth week, the epithelium of each dorsal bulbar part of the pouch begins to differentiate into an inferior parathyroid gland . The epithelium of the elongated ventral parts of the pouch proliferates, obliterating their cavities. These parts come together in the median plane to form the thymus , which is a primary lymphoid organ (see Fig. 9.7 C ). The bilobed structure of this lymphatic organ remains throughout life, discretely encapsulated.


Each lobe has its own blood supply, lymphatic drainage, and nerve supply. The developing thymus and inferior parathyroid glands lose their connections with the pharynx when the brain and associated structures expand rostrally, and the pharynx and cardiac structures expand caudally. The derivatives of pouches two to four become displaced caudally. Later, the parathyroid glands separate from the thymus and lie on the dorsal surface of the thyroid gland (see Figs. 9.7 C and 9.8 ). The fibroblast growth factor–signaling pathways, acting through fibroblast growth factor–receptor substrate 2 (FRS2), are involved in the development of the thymus and parathyroid glands.


Histogenesis of Thymus


The thymus is a primary lymphoid organ that develops from epithelial cells derived from endoderm of the third pair of pouches and from mesenchyme into which epithelial tubes grow. The tubes soon become solid cords that proliferate and form side branches. Each side branch becomes the core of a lobule of the thymus. Some cells of the epithelial cords become arranged around a central point, forming small groups of cells called thymic corpuscles (Hassall corpuscles). Other cells of the epithelial cords spread apart, but they retain connections with each other to form an epithelial reticulum. The mesenchyme between the epithelial cords forms thin, incomplete septa between the lobules.


Lymphocytes soon appear and fill the interstices between the epithelial cells. The lymphocytes are derived from hematopoietic stem cells . The thymic primordium is surrounded by a thin layer of mesenchyme that is essential for its development. Neural crest cells also contribute to thymic organogenesis.


Growth and development of the thymus are not complete at birth. It is a relatively large organ during the perinatal period and may extend through the superior thoracic aperture at the root of the neck. As puberty is reached, the thymus begins to diminish in relative size as it undergoes involution. By adulthood, it is often scarcely recognizable because of fat infiltrating the cortex of the gland; however, it is still functional and important for the maintenance of health. In addition to secreting thymic hormones, the thymus primes thymocytes (T-cell precursors) before releasing them to the periphery.


Fourth Pharyngeal Pouch


The fourth pouch expands into dorsal bulbar and elongated ventral parts (see Figs. 9.7 and 9.8 ). Its connection with the pharynx is reduced to a narrow duct that soon degenerates. By the sixth week, each dorsal part develops into a superior parathyroid gland , which lies on the dorsal surface of the thyroid gland. Because the parathyroid glands derived from the third pouches accompany the thymus, they are in a more inferior position than the parathyroid glands derived from the fourth pouches (see Fig. 9.8 ).


Histogenesis of Parathyroid and Thyroid Glands


The epithelium of the dorsal parts of the third and fourth pouches proliferates during the fifth week and forms small nodules on the dorsal aspect of each pouch. Vascular mesenchyme soon grows into these nodules, forming a capillary network. The chief or principal cells differentiate during the embryonic period and are thought to become functionally active in regulating fetal calcium metabolism. The oxyphil cells of the parathyroid gland differentiate 5 to 7 years after birth.


The elongated ventral endodermal part of each fourth pouch develops into an ultimopharyngeal body , which fuses with the thyroid gland (see Fig. 9.8 ). Its cells disseminate within the thyroid and form parafollicular cells . These cells are also called C cells, indicating that they produce calcitonin , a hormone that lowers blood calcium levels. C cells differentiate from cephalic neural crest cells that migrate from the arches into the fourth pair of pouches. The basic helix-loop-helix (bHLH) transcription factor MASH1 regulates C-cell differentiation.




Pharyngeal Grooves


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The head and neck regions of the embryo exhibit four grooves (branchial clefts) on each side during the fourth and fifth weeks (see Figs. 9.1 B to D and 9.2 ). These grooves separate the arches externally. Only one pair of grooves contributes to postnatal structures; the first pair persists as the external acoustic meatus (ear canals; see Fig. 9.7 C ). The other grooves lie in a slit-like depression (cervical sinus) and are normally obliterated along with the sinus as the neck develops (see Fig. 9.4 A , D , and F ). Birth defects of the second groove are relatively common.




Pharyngeal Membranes


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The pharyngeal membranes appear in the floors of the pharyngeal grooves (see Figs. 9.1 H and 9.3 C ). These membranes form where the epithelia of the grooves and pouches approach each other. The endoderm of the pouches and ectoderm of the grooves are soon infiltrated and separated by both neural crest cells and mesenchyme. Only one pair of membranes contributes to the formation of adult structures; the first membrane becomes the tympanic membrane (see Fig. 9.7 C ).



Cervical (Branchial) Sinuses


External cervical sinuses are uncommon, and most result from failure of the second groove and cervical sinus to obliterate ( Figs. 9.9 D and 9.10 A and B ). The sinus typically opens along the anterior border of the sternocleidomastoid muscle in the inferior third of the neck. Anomalies of the other pharyngeal grooves occur in approximately 5% of neonates. External sinuses are commonly detected during infancy because of the discharge of mucus from them (see Fig. 9.10 A ). The external cervical sinuses are bilateral in approximately 10% of affected neonates and are commonly associated with auricular sinuses.




Fig. 9.9


A , Lateral view of the head, neck, and thoracic regions of a 5-week embryo shows the cervical sinus that is normally present at this stage. B , Horizontal section of the embryo at the level shown in A illustrates the relationship between the cervical sinus and the pharyngeal arches and pouches. C , Diagrammatic sketch of the adult pharyngeal and neck regions shows the former sites of openings of the cervical sinus and pharyngeal pouches. The broken lines indicate possible tracts of cervical fistulas. D , Similar sketch shows the embryologic basis of various cervical sinus types. E , Drawing shows a cervical fistula that resulted from persistence of parts of the second groove and second pouch. F , Sketch shows possible sites of cervical cysts, the openings of cervical sinuses and fistulas, and a branchial vestige (see Fig. 9.13 ).



Fig. 9.10


A , A catheter is inserted into the external opening of a cervical sinus in a child’s neck. The catheter allows definition of the length of the tract, which facilitates surgical excision. B , After injection of contrast material, the fistulogram shows the course of a complete cervical fistula through the neck.

(Courtesy Dr. Pierre Soucy, Division of Paediatric Surgery, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada.)


Internal cervical sinuses open into the tonsillar sinus or near the palatopharyngeal arch (see Fig. 9.9 D and F ). These sinuses are rare. Most result from persistence of the proximal part of the second pouch. This pouch usually disappears as the palatine tonsil develops; its normal remnant is the tonsillar sinus.



Cervical (Branchial) Fistula


A cervical fistula is an abnormal canal that typically opens internally into the tonsillar sinus and externally in the side of the neck. The canal results from persistence of parts of the second groove and second pouch (see Figs. 9.9 E and F and 9.10 B ). The fistula ascends from its opening in the neck through the subcutaneous tissue and platysma muscle to reach the carotid sheath . The fistula then passes between the internal and external carotid arteries and opens into the tonsillar sinus.



Piriform Sinus Fistula


The piriform sinus fistula is thought to result from persistence of remnants of the ultimopharyngeal body along its path to the thyroid gland (see Figs. 9.7 C and 9.8 ).



Cervical (Branchial) Cysts


Remnants of parts of the cervical sinus and/or the second groove may persist and form a spherical or elongated cyst (see Fig. 9.9 F ). Although they may be associated with cervical sinuses and drain through them, the cysts often lie free in the neck just inferior to the angle of the mandible. However, they can develop anywhere along the anterior border of the sternocleidomastoid muscle or periauricular region. Cervical cysts do not usually become apparent until late childhood or early adulthood, when they produce a slowly enlarging, painless swelling in the neck ( Fig. 9.11 ). The cyst enlarges because of the accumulation of fluid and cellular debris derived from desquamation of their epithelial linings ( Fig. 9.12 ).




Fig. 9.11


The swelling in a boy’s neck was produced by a cervical cyst. These large cysts often lie free in the neck just inferior to the angle of the mandible, but they may develop anywhere along the anterior border of the sternocleidomastoid muscle, as in this case.

(Courtesy Dr. Pierre Soucy, Division of Paediatric Surgery, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada.)



Fig. 9.12


Computed tomography of the neck region of a 24-year-old woman with a 2-month history of a lump in the neck shows a low-density cervical cyst (C) that is anterior to the sternocleidomastoid muscle (S). Notice the external carotid artery (solid arrow) and external jugular vein (dotted arrow) .

(Courtesy Dr Gerald S. Smyser, Altru Health System, Grand Forks, ND.)



Cervical (Branchial) Vestiges


The pharyngeal cartilages normally disappear, except for parts that form ligaments or bones. However, in unusual cases, cartilaginous or bony remnants of pharyngeal arch cartilages appear under the skin in the side of the neck ( Fig. 9.13 ). They are usually found anterior to the inferior third of the sternocleidomastoid muscle (see Fig. 9.9 F ).




Fig. 9.13


A cartilaginous branchial vestige (arrow) in a child’s neck (see Fig. 9.9F ).

(From Raffensperger JG: Swenson’s pediatric surgery, ed 5, New York, 1990, Appleton-Century-Crofts.)



First Pharyngeal Arch Syndrome


Abnormal development of the components of the first arch results in various birth defects of the eyes, ears, mandible, and palate, which together constitute the first arch syndrome ( Fig. 9.14 ). This birth defect is thought to result from insufficient migration of neural crest cells into the first arch during the fourth week. There are two main manifestations of the first arch syndrome: Treacher Collins syndrome and Pierre Robin sequence.




Fig. 9.14


This infant has first arch syndrome, a pattern of birth defects that results from insufficient migration of neural crest cells into the first pharyngeal arch. Notice the deformed auricle of the external ear, preauricular appendage, defect in the cheek between the auricle and mouth, hypoplasia (underdevelopment) of the mandible, and macrostomia (large mouth).


Treacher Collins syndrome (mandibulofacial dysostosis) is an autosomal dominant disorder characterized by malar hypoplasia (underdevelopment of zygomatic bones of the face) with down-slanting palpebral fissures , defects of the lower eyelids, deformed external ears, and sometimes defects of the middle and internal ears.


The Treacher Collins–Franceschetti syndrome 1 gene (TCOF1) is responsible for the production of a protein called treacle. Treacle is involved in the biogenesis of ribosomal RNA that contributes to the development of bones and cartilage of the face. Mutation in the TCOF1 gene is associated with Treacher Collins syndrome.


Pierre Robin sequence typically occurs de novo in most patients and is associated with hypoplasia (underdevelopment) of the mandible, cleft palate, and defects of the eyes and ears. Rarely, it is inherited in an autosomal dominant pattern. In the Robin morphogenetic complex, the initiating defect is a small mandible (micrognathia) , which results in posterior displacement of the tongue and obstruction to full closure of the palatal processes, resulting in a bilateral cleft palate (see Figs. 9.40 and 9.41 ).



DiGeorge Syndrome


Infants with DiGeorge syndrome (also known as 22q11.2 deletion syndrome) are born without a thymus and parathyroid glands and have defects in the cardiac outflow tracts. In some cases, ectopic glandular tissue has been found ( Fig. 9.15 ). The disease is characterized by congenital hypoparathyroidism , increased susceptibility to infections (from immune deficiency, specifically defective T-cell function), birth defects of the mouth (shortened philtrum of upper lip), low-set and notched ears, nasal clefts, thyroid hypoplasia, and cardiac abnormalities (defects of the aortic arch and heart). Features of this syndrome vary widely, but most infants have some of the classic characteristics previously described. Only 1.5% of infants have the complete form of T-cell deficiency, and approximately 30% have only a partial deficiency.




Fig. 9.15


Anterior view of the thyroid gland, thymus, and parathyroid glands illustrates various birth defects that may occur.


DiGeorge syndrome occurs because the third and fourth pharyngeal pouches fail to differentiate into the thymus and parathyroid glands. This is the result of a breakdown in signaling between pharyngeal endoderm and adjacent neural crest cells. The facial abnormalities result primarily from abnormal development of the first arch components because neural crest cells are disrupted, and the cardiac anomalies arise in the sites normally occupied by neural crest cells. The microdeletion in the q11.2 region of chromosome 22 inactivates the TBX1 , HIRA , and UFDIL genes. Disruption of CXCR4 signaling also affects neural crest cells and leads to similar anomalies.



Accessory Thymic Tissue


An isolated mass of thymic tissue may persist in the neck and often lies close to an inferior parathyroid gland (see Fig. 9.15 ). This tissue breaks free from the developing thymus as it shifts caudally in the neck.



Ectopic Parathyroid Glands


Ectopic parathyroid glands may be found anywhere near or within the thyroid gland or thymus. The superior glands are more constant in position than the inferior ones. Occasionally, an inferior parathyroid gland remains near the bifurcation of the common carotid artery. In other cases, it may be in the thorax.



Abnormal Number of Parathyroid Glands


Uncommonly, there are more than four parathyroid glands. Supernumerary parathyroid glands probably result from the division of the primordia of the original glands. The absence of a gland results from failure of one of the primordia to differentiate or from atrophy of a gland early in development.





Development of Thyroid Gland


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The thyroid gland is the first endocrine gland to develop in the embryo. Under the influence of Notch and Hedgehog signaling pathways, it begins to form approximately 24 days after fertilization from a median endodermal thickening in the floor of the primordial pharynx. This thickening soon forms a small outpouching, the thyroid primordium ( Fig. 9.16 A ).




Fig. 9.16


Development of the thyroid gland. A and B , Schematic sagittal sections of the head and neck regions of embryos at 5 and 6 weeks, respectively, illustrate successive stages in the development of the gland. C , Similar section of an adult head and neck shows the path taken by the gland during its embryonic descent (indicated by the former tract of the thyroglossal duct).


Two lateral primordia form from the fourth pouch (ultimopharyngeal body) and fuse with the midline primordium. The lateral components primarily provide the parafollicular cell population while the midline component provides the majority of the follicular cells.


As the embryo and tongue grow, the developing thyroid gland descends in the neck, passing ventral to the developing hyoid bone and laryngeal cartilages. For a short time, the gland is connected to the tongue by a narrow tube, the thyroglossal duct (see Fig. 9.16 A and B ). At first, the thyroid primordium is hollow, but it soon becomes a solid mass of cells. It divides into right and left lobes that are connected by the isthmus of the thyroid gland ( Fig. 9.17 ), which lies anterior to the developing second and third tracheal rings.


Mar 31, 2020 | Posted by in GENERAL | Comments Off on Pharyngeal Apparatus, Face, and Neck
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