Prof Marina Kapitonova

HEAD AND NECK. DEVELOPMENT, DEFECTS and

MALFORMATIONS. Lecture for the Year 2 Dental Students

• OBJECTIVES• 1.Describe development of the skull• - neurocranium• -viscerocranium• 2.Describe development of pharyngeal arches and their

derivatives• 3.Describe development of the tongue• 4.Describe development of the face• 5.Describe congenital malformations of the head and

neck region

Primodia for the Head and Neck region:

-mesoderm (paraxial and lateral plate mesoderm)

-ectoderm (neural tube, neural crest, ectodermal placodes)

-endoderm (pharyngeal pouches originating from the pharyngeal gut – the cephalic part of the foregut)

Endoderm

Ectoderm

Angiogeniccell cluster

Prechordal

plate

Amniotic cavity

Connectingstalk

Allantois

Cloacalmembrane

Early development of the Embryo.Folding of the embryonic disc.

Early development of the Embryo.Folding of the embryonic disc.

Middle of the 3rd week – presomite stage, pan-cake appearance of embryonic disc, intraembryonic endoderm constitutes the roof of the spherical yolk sac.

Development of theDevelopment of the MesodermDevelopment of theDevelopment of the MesodermNotochord

Amnioticcavity

Mesoderm

Ectoderm

Dorsalaorta

Paraxialmesoderm

Intermediatemesoderm

Intercellularcavitiesin lateral

plate

A. day 17, initially cells of the mesodermal germ layer form a thin sheet of loosely woven tissue on each side of the midline, by 17th day cells close to the midline proliferate and form a thickened plate of tissue - paraxial mesoderm (future somites).

AA

B. day 19, more laterally, the mesoderm layer remains thin (lateral plate). Intermediate mesoderm connects paraxial and lateral plate mesoderm. Intercellular cavities in the lateral plate then appear.

BB

Amnion

Parietalmesoderm

layer

Endoderm

Neural groove

Visceralmesoderm

layerIntra-

embryoniccoelomic

cavity

Somite

Intermediatemesoderm

Endoderm

C. day 20 - intercellular cavities in the lateral plate coalesce and it is divided into two layers: the one continuous with mesoderm covering amnion (somatic or parietal mesodermal layer); and the other continuous with mesoderm covering the yolk sac (splanchnic or visceral layer).

CC

D. day 21 - space bordered by these two layers forms a newly formed cavity, the intraembryonic coelomic cavity or body cavity, which, on each side of the embryo, is continuous with the extraembryonic coelom.

DD

Development of theDevelopment of the MesodermDevelopment of theDevelopment of the Mesoderm

A :Formation and migration of neural crest cells in the spinal cord.

B: crest cells form at the tip of neural fold

                            

    

Stage 9 Appearance of Somites 1.5 - 2.5 mm19 - 21 days post-ovulationBy stage 9 the embryo from a top view resembles the sole of a shoe with the head end wider than the tail end, and a slightly narrowed middle.The first pair of somites appear at the tail and progress to the middle. One to three pairs of somites are present by Stage 9.

Human embryo, 3 weeks oldHuman embryo, 3 weeks oldHuman embryo, 3 weeks oldHuman embryo, 3 weeks old

FOLDING OF THE EMBRYOFOLDING OF THE EMBRYO FOLDING OF THE EMBRYOFOLDING OF THE EMBRYO

Pericardialcavity

Hearttube

Foregut

Hindgut

B.B. 21-22 day – cephalocaudal folding, from essentially flat pan-cake disc 21-22 day – cephalocaudal folding, from essentially flat pan-cake disc to a cylindrical configuration. to a cylindrical configuration. Tremendous growth of the future brain Tremendous growth of the future brain region results in formation of the head fold and tail fold along the region results in formation of the head fold and tail fold along the saggital plane of the embryo. saggital plane of the embryo.

BB

Development of the Body CavitiesDevelopment of the Body CavitiesDevelopment of the Body CavitiesDevelopment of the Body Cavities

Amniotic cavity

Yolk sac

Connection betweengut and yolk sac

Intraembryoniccoelomic cavity

Surface ectoderm

A.A. day 21-22, as a result of rapid growth of somites, the initial flat day 21-22, as a result of rapid growth of somites, the initial flat embryonic disk also folds laterally.embryonic disk also folds laterally.

AAAA

B.B. day 24-25, lateral foldingday 24-25, lateral folding of the embryo produces right and left lateral of the embryo produces right and left lateral folds and the embryo obtains a round appearance. Yolk stalk folds and the embryo obtains a round appearance. Yolk stalk becomes long and narrow. Embryo obtains lateral and ventral becomes long and narrow. Embryo obtains lateral and ventral abdominal walls. A narrow communication between intraembryonic abdominal walls. A narrow communication between intraembryonic coelom and extraembryonic coelom persists until the 10coelom and extraembryonic coelom persists until the 10 th th week. week.

BBBB

Folding of the EmbryoFolding of the EmbryoFolding of the EmbryoFolding of the Embryo

Buccopharyngealmembrane

Cloacalmembrane

Hearttube

Lung bud

Remnantof the

buccopharyngealmembrane

Vitelline duct

Yolk sac

Allantois

Midgut

Liverbud

C.C. 23-24 day, d23-24 day, during the head folding a part of the yolk sac is incorporated into uring the head folding a part of the yolk sac is incorporated into the embryo as a foregut which ends blindly at the oropharyngeal membrane. the embryo as a foregut which ends blindly at the oropharyngeal membrane. This membrane separates the foregut from the stomodeum (primitive mouth This membrane separates the foregut from the stomodeum (primitive mouth cavity). cavity). At the end of the At the end of the 1st month1st month this membrane ruptures thus establishing this membrane ruptures thus establishing an open connection between the amniotic cavity and the primitive gut.an open connection between the amniotic cavity and the primitive gut.

CCCC

D.D. 25 days. M25 days. More and more of the yolk sac iore and more of the yolk sac is s incorporated and the foregut incorporated and the foregut with with the hindgut lengthen at the expenthe hindgut lengthen at the expencce of the midgut.e of the midgut.

DDDD

                            

    

Embryonic DevelopmentEmbryonic Developmentof the Heart, Days 21-of the Heart, Days 21-2323. .

Embryonic DevelopmentEmbryonic Developmentof the Heart, Days 21-of the Heart, Days 21-2323. . Stage 10 reflects rapid growth and change as the embryo becomes longer and the yolk sac expands. On each side of the neural tube, between four and twelve pairs of somites can exist by the end of Stage 10.

Formation of somites (segmented blocks) at beginning of the 3rd week from paraxial mesoderm

Differentiation of somites into ventromedial sclerotome and dorsolateral dermatomyotome with subsequent ventral extension of the myotome.

Dorsal aorta

sclerotome

dermomyotome

Neural tubesclerotome

dermatome

myotome

Neural groove

ventral somitewall

notochord

coelom

sclerotome

Neural tube

Dorsal aorta

A. 14-somite embryo. Formation of pericardial bulge and pharyngeal arches

B. 25-somite embryo. Closure of neuropores. The 1st three pharyngeal arches and lens and otic placode are visible.

Segmented blocks of paraxial mesoderm

3 pairs develop per day in craniocaudal sequence

42 –44 pairs at end of 5th week

4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 8-10 coccygeal pairs of somites

1st occipital & last 5-7 coccygeal pairs disappear

Age of embryo correlated to number of somites

Formation of somitesFormation of somites (3rd –5th week)(3rd –5th week)Formation of somitesFormation of somites (3rd –5th week)(3rd –5th week)

Mesenchyme of the Head and Neck regions originates from the: 1) paraxial mesoderm (somites) – forming- the floor of the brain case- small portion of the occipital region- all the voluntary muscles of the craniofacial region,-dermis and the connective tissue of the dorsal region of the head,-meninges caudal to the prosencephalon.

Skeletal structures of the Head and Face. Blue – mesenchyme derived from the neural crest; yellow – from the lateral plate, red – paraxial mesoderm (somites)

Mesenchyme of the head region is derived from the paraxial and lateral plate mesoderm, neural crest and thickened regions of ectoderm known as ectodermal placodes. Paraxial mesoderm (somites) form the floor of the brain case and a small portion of the occipital region, all voluntary muscles of the craniofacial region and dermis and the connective tissue in the dorsal region of the head and the meninges caudal to the prosencephalon. Lateral plate forms the laryngeal cartilages (arytenoids and crycoid) and connective tissue of the region.

Mesenchyme of the Head and Neck regions originates from the: 2) lateral plate forming the laryngeal cartilages (arytenoids and crycoid) and connective tissue of the region;3) neural crest (forming midfacial and pharyngeal arch skeletal structures and all the tissue in the region – cartilage, bone, dentin, tendon, dermis, pia, arachnoid, sensory neurons, glandular stroma)4) Cells from the ectodermal placodes together with the neural crest from the neurons of the 5th, 7th, 9th, 10th cranial sensory ganglia.

Migration pathways of the neural crest cells from the fore, mid-, hindbrain into the final location (shaded) in the face and pharyngeal arches. Ectodermal placodes assist the crest cells to form the 5th, 7th, 9th and 10th cranial sensory ganglia.

A. 14-somite embryo. Formation of pericardial bulge and pharyngeal arches

B. 25-somite embryo. Closure of neuropores. The 1st three pharyngeal arches and lens and otic placode are visible.

Pharyngeal

Pharyngeal (branchial) arches appear in the 4th-5th weeks and contribute to the characteristics appearance of the embryo. Initially they consist of bars of mesenchymal tissue separated by the pharyngeal clefts.

Similtaneously with development of the arches and clefts a number of outpocketings, the pharyngeal pouches, appear along the lateral walls of the pharyngeal gut, the most cranial part of the foregut (each arch contains a cartilaginous component, a cranial nerve, and artery and a muscular component). The pouches penetrate the surrounding mesenchyme but do not establish an open communication with the external clefts Hence, though development of the arches, pouches and clefts resembles formation of gills in fishes. In human embryo real gills (brachia) are never formed. Therefore the term pharyngeal (arches, clefts, pouches) has been adopted for the human embryo.

Pharyngeal Arches

a. Frontal view of the embryo 24 days old. The stomodeum is closed by the buccopharyngeal membrane and is surrounded by the 5 mesenchymal prominences.b. Embryo at 1 month. Rupture of the buccopharyngeal membrane and formatin of he nasal placodes on the fromtonasal prominence.

Pharyngeal arches are important for neck and face development. At the end of the 4th week the center of the face is formed by stomodeum surrounded by the 1st pair of the pharyngeal arches. In 4-week old embryo 5 mesenchymal prominences can be recognized: the mandibular prominences (1st arch), caudal to stomodeum; the maxillary prominences (dorsal portion of the 1st pharyngeal arch), lateral to stomodeum; and the frontonasal prominence, a slightly rounded elevation cranial to the stomodeum.

Each pharyngeal arch consists of a core of mesenchymal tissue covered on the outside by surface ectoderm and on the inside by endodermal epithelium. In addition to mesenchyme derived from paraxial and lateral mesoderm, the core of each arch receives substantial numbers of neural crest cells, which migrate into the arches to contribute to the skeletal components of the face. The original mesoderm of the arches gives rise to the musculature of the face and neck. Thus each pharyngeal arch is characterized by its own muscular component.

PHARYNGEAL ARCHES

The muscular components of each arch have their own cranial nerve, and wherever the muscle cells migrate, they carry their nerve component with them.

Nerve supply of the pharyngeal arches

In addition each arch has its own arterial component .

Pharyngeal pouches as outpocketings of the foregut and the primodium of the thyroid gland and aortic arches).

pharyngeal arch

nerve muscles skeleton

1.Mandibular (maxillary and mandibular processes)

V.Trigeminal (maxillary and mandibular divisions

Mastification (temporal; masseter; medial, lateral pterygoids); mylohyoid; anterior belly of digastrics; tensor palatine, tensor tympani

Premaxilla, maxilla, zygomatic bone, part of the temporal bone, Meckel’s cartilage, mandible malleus, incus, anterior ligament of malleus, sphenomandibular ligament

2.Hyoid VII.Facial Facial expression (buccinator, auricularis, frontalis, platisma, orbicularis oris, orbicularis oculi); posterior belly of digastrics; stylohyoid; stapedius

Stapes; styloid process; stylohyoid ligament; lesser horn and upper portion of body of hyoid bone

3. IX.Glossopharyngeal Stylopharyngeus Greater horn and lower portion of the body of the hyoid bone

4-6 X.Vagus – superior laryngeal branch (nerve to 4th arch. Recurrent laryngeal branch (nerve to 6th arch)

Cricothyroid; levator palatine; constrictors of pharynxIntrinsic muscles of larynx

Laryngeal cartilages (thyroid, cricoids, arytenoids, corniculate, cuneiform)

Derivatives of the Pharyngeal arches

1st arch consists of a dorsal portion, the maxillary process, which extends forward beneath the region of the eye, and a ventral portion, the mandibular process, which contains Merckel’s cartilage. Maxillary process and Merckel’s cartilage are replaced by the maxilla and mandible respectively which develop by membranous ossification. …

Lateral view of the head and neck in 4-week embryo: cartilages of the arches forming the bones of face and neck

Merckel’s cartilage will later disappear except for 2 small portions at its dorsal end that persists and form incus and malleus . Mesenchyme of the maxillary process gives rise to premaxilla, maxilla, zygomatic bone and part of temporal bone through membranous ossification . The mandible is also formed by membranous ossification of the mesenchyme around the Merckel’s cartilage.

Various components of the pharyngeal arches later in development. Some of the components ossify, others disappear and become ligamentous.

Definite structures formed by the cartilaginous components of the arches.

In addition the 1st arch contributes to formation of the bones of the middle ear.

Masculature of the 1st arch includes: muscles of mastication (temporalis, masseter, pterygoids), anterior belly of the digastrics, mylohyoid, tensor tympani, tensor palatini supplied by the mandibular branch of the CN5. Since mesenchyme from the 1st arch also contributes to the dermis of the face, sensory supply to the skin of the face is provided by the ophthalmic, maxillary and mandibular branches of the trigeminal nerve. Muscles of the arches do not always attach to the bony or cartilagenous components of their own arch but sometimes migrate into surrounding regions. Nevertheless, the origin of these muscles can always be traced, since the nerve supply is derived from the arch of the origin.

2nd arch. The cartilage of the 2nd arch (hyoid) (Reicher’s cartilage) gives rise to the stapes, styloid process of the temporal bone, stylohyoid ligament and ventrally to lesser horn and upper part of the body of the hyoid bone. Muscles of the 2nd arch: stapedius, stylohyoid, posterior belly of the digastrics, auricular, muscles of the facial expression, they are all supplied by the facial nerve. 3rd arch’s cartilage produces lower part of the body and greater horn of the hyoid

The musculature is limited to the stylopharyngeus muscles innervated by the glossopharyngeal nerve.

4th and 6th arches’ cartilaginous components fuse to form thyroid, cricoids, arytenoids, corniculate and cuneiform cartilages of the larynx . Muscles of the 4th arch (crycothyroid, levator palatine, constrictors of the pharynx) are innervated by the superior laryngeal branch of the vagus. Intrinsic muscles of the larynx are supplied by the recurrent laryngeal branch of the vagus, the nerve of the 6th arch.

Pharyngeal pouches.The human embryo has 5 pairs of pouches. The last one of these is atypical and often considered as part of the 4th. Epithelial endodermal lining of the pouches gives rise to a number of organs.1st pouch. The 1st pouch form a stalk-like diverticulum, the tubotympanic recess, which comes in contact with the epithelial lining of the 1st cleft, the future external auditory meatus. The distal portion of the diverticulum widens into a saclike structure, the primitive tympanic or middle ear cavity, and the proximal part remains narrow, forming the auditory (Eustachian) tube. The lining of the tympanic cavity later aids in formation of the tympanic membrane or eardrum.

Pharyngeal Pouches

2nd pouch. The epithelial lining of the 2nd pouch proliferates and forms buds that penetrate into the surrounding mesenchyme. The buds are secondarily invaded by mesenchymal tissue, forming the primodium of the palatine tonsil. During the 3rd and the 5th month the tonsil in infiltrated by the lymphoid tissue. Part of the pouch remains and is found in the adult as the tonsillar fossa.3rd pouch. The 3rd and the 4th pouches are characterized as their distal extremity by a dorsal and ventral wing.In the 5th week epithelium of the dorsal of the 3rd pouch differentiates into the inferior parathyroid glands while the ventral wing forms the thymus.

2nd and 3rd pouches

Migration of the thymus, parathyroid glands and ultimobranchual body.

ultimibranchial bodies

thymus

thyroid

superior parathyroid

(from 4th pouchinferior

parathyroid (from 3rd pouch

foregut

Foramen cecum

palatine tonsil

auditory tube

primitive tympanic cavity

6 weeks

Both gland primodia loose their connection with a pharyngeal wall and the thymus then migrates to caudal and medial direction, pulling the inferior parathyroid with itAlthough the main portion of the thymus moves rapidly to its final position in the anterior part of the thorax, where it fuses with its counterpart from the opposite side, its tail portion sometime persists either embedded in the thyroid gland or as isolated thymic nests.

Growth and development of the thymus continue until puberty. In the young child the thymus occupies considerable space in the thorax and lies behind the sternum and anterior to the pericardium and great vessels. In older persons it is difficult to recognize, since it is atrophied and replaced by fatty tissue.

DEVELOPMENT OF THYMUS

The parathyroid tissue of the 3rd pouch finally continues to rest on the dorsal surface of the thyroid gland and forms the inferior parathyroid gland4th pouch. Epithelium of the dorsal wing of the 4th pouch forms the superior parathyroid gland. When it loses contact with the wall of the pharynx, it attaches itself to the dorsal surface of the caudally migrating thyroid as the superior parathyroid gland.

3rd and 4th Pouches

..

DevelopmenDevelopment of thymust of thymus

Maxillary process

Mandibular process

Pharyngealclefts

External auditory meatus

Palatine tonsil

Parathyroid glandinferior

Thymus

Parathyroid gland superior

Pharyngeal pouches

5th pouch. It is usually considered as a part of the 4th pouch, it is the last to develop. It gives rise to the ultimobranchial body which is later incorporated into the thyroid gland. Cells of the ultimobranchial body give rise to the C-cells of the thyroid gland secreting calcitonin.

The 5-week embryo is characterized by the presence of the 4 clefts of which only one contributes to the definite structure of the embryo. The dorsal part of the 1st cleft penetrates the underlying mesenchyme and gives rise to the external auditory meatus. The epithelial lining at the bottom of the meatus participates in the formation of the eardrum. Active proliferation of the mesenchyme in the 2nd arch causes it to overlap the 3rd and the 4th arches. Finally it merges with the epicardial ridge in the lower part of the neck, and the 2nd, 3rd, 4th clefts lose contact with the outside. The clefts form a cavity lined with ectodermal epithelium, the cervical sinus, but with further development this sinus disappears.

Pharyngeal clefts.

DEVELOPMENT OF THE TONGUEDEVELOPMENT OF THE TONGUE Stage 12. Stage 12. Day 26-27Day 26-27

floor offloor of pharynxpharynx

foramen caecum

copula=hypobrachial

eminence

laryngotracheal groove

copola

The tongue appears in 3 weeks as the two lateral lingual swelling and one medial swelling, the tuberculum impar, all originate from the 1st pharyngeal arch. A 2nd median swelling – the copola or hypobranchial eminence, is formed by the mesoderm of the 2,3, and part of the 4th arch.

lingual swelling

tuberculum impar

foramen caecum

hypobranchial eminence

epiglottalswelling

arytenoid swellings

laryngotracheal groove

The 3rd median swelling formed by the posterior part of the 4th arch marks development of the epiglottis. Behind this swelling is the laryngeal orifice which is flanked by the arytenoids swelling.

DEVELOPMENT OF THE TONGUE DEVELOPMENT OF THE TONGUE

Development of the tongue.As the lateral lingual swellings increase in size they overgrow the tuberculum impar and merge, forming the anterior two-thirds of the tongue. Since mucosa of the body of the tongue originates from the 1st arch, sensory innervations is by the mandibular branch of the trigeminal nerve. The posterior part of the tongue separated by sulcus terminalis originates from the 2nd.3rd and part of the 4th arch. Tissue of the 3rd arch overgrows that of the 2nd, as a result sensory innervations is supplied by the glossopharyngeal nerve.

Foramencecum

Body of tongue

Epiglottis

Arytenoid swellings

Lingual swelling

Epiglottalswelling Laryngeal

orifice

Development of the tongue.

Foramencecum

Body of tongue

Epiglottis

Arytenoid swellings

Lingual swelling

Epiglottalswelling

Laryngealorifice

The epiglottis and the extreme posterior part of the tongue are innervated by the superior laryngeal nerve reflecting its development from the 4th arch. Most of the tongue muscles derive from the myoblasts of the occipital somites. Thus tongue muscles are innervated by the hypoglossal nerve. So, the sensory innervations: the body is supplied by the trigeminal nerve, the nerve of the 1st arch; the root – by the glossopharyngeal and vagal nerves, the nerves of the 3rd and 4th arches respectively. Special sensory innervations (taste) to the anterior 2/3s is provided by chorda tympani branch of the facial nerve while the posterior third is supplied by the glossopharyngeal nerve.Tongue-tie (ankyloglossia) is a result of the failure of cells to degenerate at the floor of the mouth. That is why frenulum extends to the tip of the tongue and the tongue is not freed from the floor of the mouth.

5th Pouch

DEVELOPMENT OF LARYNXDEVELOPMENT OF LARYNX

The epiglottis is a derivative of the caudal part of the midline hypobranchial eminence which is produced by the proliferation of the 3rd and 4th branchial arch mesenchyme. As the mesenchyme proliferates, the epiglottal swelling and the two arytenoid swellings convert aditus from a linear to a T-shaped entrance.

STAGE 1637th day, 11-14 mm

STAGE 2356th day, 23-32 mm

WEEK 10

epiglottalswelling

primitiveglottis

arytenoid swelligs

epiglottis

cuneiformtubercle

interarytenoid notch

TONGUE TONGUE

CONGENITAL MALFORMATION OF THE PHARYNGEAL REGION1.Ectopic thymic and parathyroid gland ( a result of migration of the glandular tissue derived from the pouches. (thymus may remain in the neck, parathyroid glands, especially inferior ones may remain at the bifurcation of the common carotid artery).

2.Branchial fistulas – provide drainage for a lateral cervical cysts which are the remnants of the cervical sinus, located on the lateral aspect of the neck anterior to the sternocleidomastoid muscle below the angle of the jaw. Often invisible at birth but later may grow and become prominent. They occur when the 2nd arch fails to grow caudally over the 3rd and 4th arches thus leaving the remnants of the 2nd, 3rd and 4th clefts in contact with the surface.

Thyroglossal duct may persist giving rise to the thyroglossal cysts. They may lie at any point along the migratory pathway of the thyroid gland but are always near or in the midline of the neck. Although approximately 50% of these cysts are close to or just inferior to the body of the hyoid bone, they may also be found at the base of the tongue or close to the thyroid cartilage.

Sometimes a thyroglossal cyst is connected to the outside by a fistulous canal, a thyroglossal fistula. Such a fistula usually arises secondarily after rupture of a cyst but may be present at birth.

Development of the Thyroid Gland – Clinical Correlations

Thyroglossal CystThyroglossal Cyst Thyroglossal cysts are the cystic remnants of the thyroglossal duct. They are commonly found behind the arch of the hyoid bone. An important diagnostic characteristic is their midline location. Thyroglossal cyst is a painless progressively enlarging movable mass. The cyst may contain some thyroid tissue.

Thymic anomalies.1. Cervical thymus. A cord of thymic or fibrous

tissue may persist in the neck along the pathway of descent. Rarely the thymus, or at least its left-sided primodium, may remain in the neck.

2. Accessory thymus. A portion of the thymus may become separated from the main mass during descent. Alternatively, accessory thymic tissue may arise from pharyngeal pouch 4 and become anchored to the superior parathyroid or become embedded in the thyroid gland.

3. Myasthenia gravis. This autoimmune disease caused by disfunction of acetylcholine receptors, is benefited by thymectomy.

Disturbances in the embryologic development of the Disturbances in the embryologic development of the thymus may give rise to a series of congenital anomalies thymus may give rise to a series of congenital anomalies and malformation. One of the most frequently and malformation. One of the most frequently encountered is the presence of parathyroid gland tissue encountered is the presence of parathyroid gland tissue within the thymus.within the thymus.

Ectopic parathyroid tissue adjacent to normal thymic glandEctopic parathyroid tissue adjacent to normal thymic gland

Thymic anomalies.

Di George Sequence (3rd and 4th pharyngeal pouch syndrome) – neural crest cells defect – includes hypoplasia or absence of thymus (crest cells contribute to the connective tissue of the gland), and/or parathyroid gland with or without CVS defects (persistent truncus arteriosus, interrupted aortic arch), abnormal external ears, micrognatia and hypotelorism (widely spaced eyes). Patients with complete DiGeorge sequence have immunological problems, hypocalciemia and poor prognosis. DiGeorge sequence occurs sporadically and may involve teratogens, such as the retinoids.

DiGeorge Syndrome

Note Note hypotelorism hypotelorism and small jaw.and small jaw.

DiGeorge SyndromeDiGeorge Syndrome

Note abnormal Note abnormal ear. This child ear. This child has an has an interrupted interrupted aortic arch.aortic arch.

Development of NoseDevelopment of Nose

C – C – during 5th week they invaginate to form nasal pits.

B – B – on both sides of frontonasal prominence nasal (olfactory) placodes originate under inductive influence of the forebrain,

frontonasal prominence maxillary prominence mandibular prominence

stomodeum

heart prominence

lens placode

nasal placode

stomodeum

hyoid arch

nasal piteye

nasolacrimalgroove

24 +/- 1 day

28 +/- 1 day

31 +/- 1 day

B

C

A A1

B1

C1

branchialarches:

1 st2 nd

Frontal view of a 4 ½-week old embryo. Nasal placodes are visible on either side of the frontonasal prominence.

Development of Face in Human Embryo, SEM Development of Face in Human Embryo, SEM

nasal pit

mediallateral

nasal prominences

nasolacrimal groove

first branchial groove

medial nasal prominence

lateral nasal prominence

external ear

DD

EE

DD11

EE11

33 +/- 1 day

35 +/- 1 day

DEVELOPMENT OF NOSEDEVELOPMENT OF NOSE

E – E – nasal pits are still two separate plates, but they rotate to face ventrally as head widens.

D – D – a ridge of tissue around each nasal pit forms nasal prominences:medial and lateral. Lateral nasal and maxillary prominences are separated by nasolacrimal groove. After detachment of the cord forming naso-lacrimal duct, from the floor of the groove, the maxillary and lateral nasal prominences merge.

Development of Face in Human Embryo, SEM Development of Face in Human Embryo, SEM

Frontal view of a 6-week old embryo. Nasal prominences are separated from the maxillary prominence by deep furrows.

eyelid

nostril

lowerjaw

eyelid

medial nasalprominences mergingwith each other and

maxillary prominences

40 +/- 1day

48 +/- 1day

FF FF11

GGGG11

In weeks 5-8 the maxillary prominences increase in size, and the medial nasal prominences move medially and merge to form the intermaxillary segment which includes nasal septum. As a result of medial growth of maxillary prominences the two medial nasal prominences merge not only at a surface but also at deeper level.

Development of Nose Development of Nose

Development of Face in Human Embryo, SEMDevelopment of Face in Human Embryo, SEM

Frontal view of a 7-week old embryo. Maxillary prominences have fused with the medial nasal prominence.

Nose is formed from the 5 facial prominences: the frontal prominence gives rise to the bridge, the merged medial nasal prominences provide crest and tip, the lateral nasal prominences form the sides (alae).

DEVELOPMENT OF NOSEDEVELOPMENT OF NOSE

nasolacrimalgroove

intermaxillarysegment

philtrum of lip

HH

II

HH11

II11

10 weeks

14 weeks

Development of Nasal CavitiesDevelopment of Nasal Cavities

B – B – During 7th week oro-nasal membrane ruptures bringing nasal and oral cavities into communication.

Wall of brain

Nasalpit

Medialnasal

prominence

Oronasalmembrane

Oral cavity

Tongue

Breakdown oforonasal membrane

Oralcavity

Tongue

AA BB

A - A - During 6th week the nasal pits deepen considerably because of growth of nasal prominences and partly because of their penetration into underlying mesenchyme. It results in the formation of the primitive nasal sacs. Initially they are separated from the oral cavity by oro-nasal membrane.

Nasalchamber

Primitivechoana

Primary palate

Maxilla

Upper lip

Lower lip

Mandible

Conchae

Secondarypalate

Definitivechoana

C – C – in 7- week embryo the regions of continuity between nasal and oral cavities are primary choanae (openings between nasal cavity and nasopharynx). Primitive choanae are located on each side of midline behind the primitive palate formed by intermaxillary segment.

CC

D D – in 9- week embryo with formation of the secondary palate, separating oral and nasal cavities, and further development of nasal chambers, definite choanae are located at the junction of nasal cavity and nasopharynx. Ectodermal epithelium in the roof of each nasal cavity becomes specialized to form olfactory epithelium.

DD

Development of Nasal CavitiesDevelopment of Nasal Cavities

It originates from the three primodiums – the median palatine process (primary palate) and the two lateral palatine processes.

DEVELOPMENT OF PALATEDEVELOPMENT OF PALATE

Formation of the palate is one of the last major morphogenetic events to occur (Week 5-12) in embryo and fetus..

Secondary palate develops after the lateral palatine processes (shelves) fuse with each other and nasal septum.

Development of Secondary PalateDevelopment of Secondary Palate

Nasalseptum

Tongue

Nasalchamber

Palatine shelf

Primary palate

Nasalseptum

AA – in 6-week embryo the two lateral outgrowths appear at the – in 6-week embryo the two lateral outgrowths appear at the maxillary prominence. They are directed obliquely downward on each maxillary prominence. They are directed obliquely downward on each side of the tongue.side of the tongue.

AA

B – cleft between the primary palate and the palatine shelves. B – cleft between the primary palate and the palatine shelves.

BB

Development of Secondary PalateDevelopment of Secondary Palate

Nasalseptum

Oralcavity

Tongue

Palatine shelf

Primarypalate

Eve

Nasal chamber

AA – in the 7 ½ week embryo the palatine shelves ascend to attain a – in the 7 ½ week embryo the palatine shelves ascend to attain a horisontal position above the tongue and fuse with each other horisontal position above the tongue and fuse with each other forming the secondary palate.forming the secondary palate.

AA

BB – the wedge-shaped median palatine process fuses with lateral – the wedge-shaped median palatine process fuses with lateral palatine processes and the nasal septum. palatine processes and the nasal septum.

BB

Development of Secondary PalateDevelopment of Secondary Palate

Bone gradually develops in the primary palate, formimg the premaxillary part Bone gradually develops in the primary palate, formimg the premaxillary part of the maxilla. Bone formation in the anterior portion of the fused lateral of the maxilla. Bone formation in the anterior portion of the fused lateral palatine processes creates the hard palate.palatine processes creates the hard palate.The palate posterior to the hard palate forms the soft palate and uvula. The palate posterior to the hard palate forms the soft palate and uvula.

Nasalconchae

Tongue

Nasal chamber

Nasal septum

Fusedpalatal shelves

Oral cavity

Incisiveforamen

Uvula

AA – in 10 week embryo the two palatine shelves fuse with each other and with – in 10 week embryo the two palatine shelves fuse with each other and with the nasal septum. The superior, middle and inferior conchae develop as the nasal septum. The superior, middle and inferior conchae develop as elevations on the lateral walls of the nasal cavities.elevations on the lateral walls of the nasal cavities.

AA

BB - the incisive foramen forms the midline between the primary and - the incisive foramen forms the midline between the primary and secondary palate.secondary palate.

BB

7. Cleft lip occurs when mesenchyme of the intermaxillary segment fails to merge with the maxillary prominence (may be uni- or bilateral, associated with cleft palate or not).

CLINICAL CORRELATESCLINICAL CORRELATES

1. Congenital anomalies of face and palate are common due to the complicated course of development of the region.

2. They result from maldevelopment of neural crest tissue that gives rise to the skeletal and CT- primodia of face.

3. They result from arrest of development and/or a failure of fusion of the prominences and processes involved.

4. Cleft lip and cleft palate occuring together or separately are the most common defects of the face.

5. They may occur as a result of either genetic inheritance or environmental factors.

6.6. Cleft lip refers to the failure of fusion of the hard and/or soft lateral palatine processes with each other and/or nasal septum and/or the median palatine process.

lipIncisivepapilla

hardpalatesoft

palate

uvula cleft uvula

nasalcavity

nasalseptum

CLEFT PALATECLEFT PALATE

A. normal lip and palate,

AA

B. cleft uvula (fish tail appearance),

BB

C. unilateral cleft of the secondary palate: results from failure of mesenchimal masses in the lateral palatine processes to meet with each other and nasal septum,

CC

D. bilateral cleft of the secondary palate.

DD

CLEFT LIP AND CLEFT PALATECLEFT LIP AND CLEFT PALATE

primary palate

site ofIncisiveforamen

secondarypalate

E. complete unilateral cleft of the lip and alveolar process of the maxilla with unilateral cleft of the anterior palate – results from failure of mesenchymal masses in the palatine shelves to meet and fuse with the mesenchyme in the primary palate,

EE

F. complete bilateral cleft of the lip and alveolar process of the maxilla with bilateral cleft of the anterior palate.

FF

CLEFT PALATECLEFT PALATE

G. Complete bilateral cleft of the lip and alveolar process of the maxilla with bilateral cleft of the anterior palate and unilateral cleft of the posterior palate – results from failure of mesenchymal masses in the palatine shelves to meet and fuse with the mesenchyme in the primary palate, with each other, and with the nasal septum,

GG

H. Complete bilateral cleft of the lip and alveolar process of the maxilla with complete bilateral cleft of the anterior and posterior palate.

HH

CAUSES OF CLEFT LIP AND PALATE

-Most cases of facial clefts are the result of the multiple factors, genetic and non-genetic, each causing a minor developmental disturbances.

-This is called multifactorial inheritance.

-Some clefts appear as a part of syndromes determined by single mutant genes, other clefts are parts of chromosomal syndromes, such as trisomy 13.

-A few cases appear to have been caused by teratogenic agents (e.g., anticonvulsant drugs).

-Vitamin B given to pregnant women who are at risk for cleft palate, might decrease the occurance of facial clefting in the offspring.

Photographs illustrating various types of cleft lip. A and B, Unilateral cleft lip. The cleft in B is Incomplete; the arrow indicators a band of tissue (Simonart’s band) connecting the cleft of the lip. C and D, Bilateral cleft lip. (Courtesy of Dr. D.A.Kernahan, The Children’s Memorial, Chicago.)

Photographs illustrating congenital anomalies of the lip and palate. A, Complete unilateral cleft of the lip and alveolar process. B, Complete bilateral cleft of the lip and alveolar process with bilateral cleft of the anterior palate. C and D, Bilateral cleft of the posterior or secondary palate; the lip is normal.