📚 Question Bank

The given scenario is suggestive of Treacher Collins syndrome that results from abnormal development of the 1st pharyngeal arch (mandibular arch).

First arch syndromes are congenital defects caused due to the failure of the neural crest cells to migrate into the 1st pharyngeal arch. They are:

• Treacher-Collins syndrome (mandibulofacial dysostosis) - Autosomal dominant genetic disorder characterized by:
• Craniofacial bone defects - Involves mandible (causing micrognathia), maxilla, and zygomatic arches
• Ear defects - Involves the external ear, atresia of auditory canals, and abnormalities of the middle ear ossicles leading to bilateral conductive hearing loss
• Eye defects - Down-slanting palpebral fissures and lower eyelid colobomas
• Pierre Robin sequence (or Robin sequence) - Caused due to genetic defects or due to environmental factors. It can also be seen in oligohydramnios when the chin gets compressed against the chest in utero.
• It is characterized by a triad of micrognathia, glossoptosis (posteriorly placed tongue), and
• cleft palate
• The primary defect is poor growth of the mandible (micrognathia)
• As a consequence of this, the tongue is posteriorly placed (glossoptosis)
• Additionally, the tongue remains in between the palatal shelves and they fail to fuse (cleft
• palate)

Greater cornu (greater horn) is derived from the 3rd pharyngeal arch.

The lower part of the body of the hyoid bone is also formed from 3rd pharyngeal arch.

In the above scenario, the cricothyroid muscle is affected since it is responsible for high pitch phonation. It is derived from the 4th pharyngeal arch.

All the other intrinsic muscles of the larynx arise from the 6th pharyngeal arch.

Pharyngeal A rch

I

II

III IV

VI

Muscle derivatives

Muscles of mastication, mylo hyoid, anterior belly of digast ric, tensor tympani, and tens or veli palatini

Muscles of facial expression, stapedius, stylohyoid, platys ma, and posterior belly of dig astric

Stylopharyngeus

Larynx - cricothyroid; soft pa late - levator veli palatini; ph aryngeal constrictors

Larynx - All intrinsic muscles

(except cricothyroid)

The given clinical scenario of congenital hypoparathyroidism and thyroid hypoplasia, absent thymus on CT scan is suggestive of DiGeorge syndrome. The defect is most likely to be present in the development of third and fourth pharyngeal pouches.

Structures derived from various pharyngeal pouches (I-IV) are:

Calcitonin produced by parafollicular C-cells of the thyroid which is derived from the ultimobranchial body (4th pharyngeal pouch derivative).

The 4th pharyngeal pouch develops a small diverticulum medial to the main pouch called the ultimobranchial body. The ultimobranchial body is later incorporated into the thyroid gland and its cells give rise to the parafollicular or C-cells of the thyroid gland. These cells secrete a hormone called calcitonin that is involved in the regulation of the calcium level in the blood.

Clinical consideration: Both chromaffin cells of the adrenal medulla and parafollicular cells

(C-cells) of the thyroid originate from the neural crest cells. A common, germ-line mutation in neural crest cells can cause tumors in both the adrenal medulla and the thyroid, as seen in MEN types 2A and 2B.

The diagnosis according to the given clinical vignette is acute tonsillitis affecting palatine tonsils. They are derived from the 2nd pharyngeal pouch.

The epithelium of the 2nd pharyngeal pouch proliferates to form solid cords known as tonsillar buds. The tonsillar buds penetrate into the surrounding mesoderm. These buds are then invaded by the mesodermal tissue to form the palatine tonsil. The capsule of the tonsil is formed by the condensed mesoderm. During the 3rd and 5th months, the tonsil is infiltrated by lymphatic tissue.

The intratonsillar cleft (tonsillar fossa) is the remnant of the 2nd pharyngeal pouch found in the adult.

The foramen cecum indicates the site of development of thyroid.

The thyroid gland develops as a midline derivative of the pharynx between the 1st and

2nd pharyngeal pouches. Around the 5th week, a midline diverticulum is formed just caudal to the median tongue bud, at the site where foramen cecum is found later. This midline diverticulum passes caudally as the thyroglossal duct in front of the hyoid bone. The tip of this thyroglossal duct divides into two and their tissue mass proliferates to form the thyroid.

Tissues of the thyroid and their origin:

• The epithelial tissue of the thyroid gland is derived from endoderm.
• The connective tissue of capsule and interlobular septa are derived from the neural crest mesenchyme.
• The parafollicular or C cells are derived from the ultimobranchial body, a small diverticulum of the 4th pharyngeal pouch.

Remnants of the thyroglossal duct can result in the formation of the thyroglossal cyst or fistula.

The given scenario is suggestive of a branchial cyst that develops due to the persistence of the cervical sinus.

The cervical sinus is formed when the 2nd arch mesoderm overgrows the succeeding arches and overhangs them as shown in the image. The space between the overhanging 2nd pharyngeal

arch and the 3rd, 4th, and 6th arches is called the cervical sinus. The cavity of the cervical sinus is lined by ectoderm and normally gets obliterated.

In some individuals, a part of the cervical sinus may persist and give rise to swellings known as branchial cysts. It is present in the neck along the anterior border of the sternocleidomastoid muscle. These cysts are most commonly located just below the angle of the mandible. If the branchial cyst opens onto the surface, it becomes a branchial sinus.

The structure marked “1” is the outer annulus fibrosus and "2" is the inner nucleus pulposus of the intervertebral disc. They develop from the sclerotome and notochord, respectively.

The vertebral bodies and the annulus fibrosus (peripheral part of the intervertebral disc) are derived from the mesenchymal cells of the sclerotome.

The nucleus pulposus is a remnant of the notochord. The notochord regresses entirely in the region of vertebral bodies, but it persists in the central part of the intervertebral discs as

the nucleus pulposus.

The correct order of heart tube structures from cranial to caudal is bulbus cordis, primitive ventricle, primitive atrium, and the sinus venosus.

The 2 heart tubes formed in the cardiogenic area fuse, except in their caudal most end, to become an inverted Y-shaped structure. During this fusion, the central part of the heart tube expands to form the future outflow tract and ventricular regions. The caudal pole of the tube receives the venous drainage, while the cranial end pumps out blood into the arterial system.

The post-renal segment of the inferior vena cava (IVC) mainly develops from the right supracardinal vein.

In embryonic life, the supracardinal veins get a large amount of venous drainage from the growing body wall. The right supracardinal vein persists and forms the greater part of the postrenal segment of the inferior vena cava.

The inferior vena cava is a composite vessel that develops from the remodeling of successive venous complexes. The veins contributing to the formation of IVC from upwards to below are as follows:

• Cardiac termination of the right vitelline vein, also known as the right hepatocardiac channel
• Anastomosis between right vitelline and right subcardinal veins (Hepatic segment of IVC)
• Right subcardinal vein (Subcardinal or Pre-renal segment of IVC)
• Anastomosis between right supracardinal and right subcardinal veins (Renal segment of IVC)
• Part of the right supracardinal vein (Supracardinal or Post-renal segment of IVC)
• Anastomosis between right supracardinal and right postcardinal veins
• Part of the right posterior cardinal vein
• Common iliac veins

The superior vena cava is not derived from the vitelline vein.

Vitelline veins are developmental vessels passing between the yolk sac and the sinus venosus of the heart. Vitelline veins contribute to the development of the following structures:

• Hepatic vein: Before entering the sinus venosus, the vitelline veins form a plexus around the duodenum and pass through the septum transversum. The liver cords grow into the septum breaking the course of this vein into an extensive vascular network known as hepatic sinusoids.
• The sinusoids form the hepatic vein and drain into the inferior vena cava.
• Portal vein: The anastomotic plexus formed by the vitelline veins around the duodenum develops into a single vessel called the portal vein.
• Inferior vena cava: The hepatocardiac portion of IVC develops from the right hepatocardiac channel, which is derived from the right vitelline vein.
• Superior mesenteric vein: This vein is derived from the right vitelline vein and drains the primary intestinal loop.

The ductus arteriosus gets functionally closed through contraction of its muscular wall almost immediately after birth. However, anatomical closure occurs only 2-3 weeks after birth.

In fetal life, prostaglandins relax the vascular smooth muscle and keep the ductus arteriosus open.

After birth, there is high oxygen content in the blood due to ventilation in the lung. This inhibits the production of prostaglandins. The ductus closes due to vascular smooth muscle contraction leaving a ligamentous remnant known as ligamentum arteriosum.

Note: Premature infants can be treated with prostaglandin synthesis inhibitors (such as indomethacin) to promote closure of the ductus arteriosus.

The egg-on-a-string appearance on chest X-ray is characteristically seen in the transposition of great arteries (TGA). It is considered to arise due to abnormal spiraling of the aortopulmonary septum (conotruncal septum).

In this condition, the aortopulmonary septum fails to follow the normal spiral course and instead runs straight. This results in aorta arising from the right ventricle and the pulmonary trunk from the left ventricle. This condition is seen in 4.8/10,000 births.

Patent ductus arteriosus is commonly seen along with this condition. Sometimes, there is an associated defect in the membranous part of the interventricular septum.

The correct order of phases of lung maturation is as follows: embryonic, pseudoglandular, canalicular, saccular phase.

The development and maturation of the lungs occur mainly in the following phases:

Phase

Embryonicphase (0–7 weeks)

Pseudoglandularphase (7–17 weeks)

Canalicularphase (17–27 wee ks)

Saccularphase/Alveolarphase

(28–32 weeks to after birth)

Developmental events

Appearance of lung buds and the main pulmonary arteries

Development of airways and blood vessels to the level of t he acinus

Formation of respiratory air ways and the development of the blood-air barrier

Development and secondary septation of alveoliAdjacent c apillary networks fuse to for m an extensive double capilla ry network

The mouth is bidermal and derived partly from the stomatodeum (ectoderm) and partly from the cranial part of the foregut (endoderm).

The buccopharyngeal membrane, which is the demarcation between ectoderm and endoderm disappears by 4th week of development. The ectodermal and endodermal layers then become continuous with each other.

The primitive gut is endodermal in origin.

When the cephalocaudal and lateral folding of the embryo occurs, a section of the endodermal germ layer gets enclosed within the embryo to form a tube-like structure called the primitive gut. The cephalic and caudal parts of the primitive gut end blindly are now known as the foregut and hindgut, respectively. The middle part is known as the midgut and is connected to the yolk sac through the vitelline duct.

The duodenum develops from both the caudal part of the foregut and the cranial part of the midgut.

Structures originating from different sections of the primitive gut are as follows:

• Foregut: pharynx, esophagus, stomach, duodenum (proximal), liver, gall bladder, pancreas
• Midgut: duodenum (distal), small intestine (jejunum, ileum), appendix, cecum, ascending colon, proximal 2/3rd of transverse colon
• Hindgut: distal 1/3rd of transverse colon, descending colon, proximal part of the rectum. From the cloaca (caudal part of hindgut) arise the distal part of the rectum and upper part of the anal canal.

Failure of the intestinal loops to return to the abdominal cavity during the 6th to 10th weeks results in omphalocele or exomphalos.

Omphalocele is a congenital malformation in which the abdominal viscera protrudes through a wide umbilical defect. The bowel loops are covered by amnion.

A small omphalocele contains only the intestines. A large omphalocele may contain other viscera such as the stomach, liver, spleen, and large intestine, along with the small intestine. Omphalocele is commonly associated with other congenital anomalies (e.g., trisomy 13, trisomy 18, or

Beckwith-Wiedemann syndrome) and causes increased levels of α-fetoprotein.

The images given below shows the omphalocele.

Note: Gastroschisis is the major disorder to consider in the differential diagnosis of an omphalocele. It can be differentiated from omphalocele by its absence of a membranous sac and paraumbilical location (commonly to the right of the umbilicus).

Septum transversum develops from the mesoderm.

Septum transversum is a thick mass of mesodermal tissue that occupies the space between the developing thoracic cavity and yolk stalk in the early embryo. It works as a partition to separate thoracic and abdominal cavities.

The septum transversum gives rise to:

• The central tendon of the diaphragm
• The ventral mesentery of the foregut
• The connective tissue of the liver

Failure of fusion of the dorsal and ventral pancreatic buds leads to a condition called pancreas divisum.

The developing pancreatic ducts usually fuse in such a way that most of the dorsal duct drains into the proximal part of the ventral duct. The proximal portion of the dorsal duct usually persists as an accessory duct. In about 10 of the population, the two ducts do not fuse, resulting in pancreatic divisum (pancreas divisum) where separate drainage into the duodenum is maintained.

The image given below shows the development of the pancreas.

The annular pancreas occurs when the right portion of the ventral bud migrates along its normal route, but the left migrates in the opposite direction. In this case, the duodenum is surrounded by pancreatic tissue.