D R . A D H I T A D W I A R Y A N T I , . M . K E S

TERATOLOGY OF DIGESTIVE SYSTEM

FACIAL ABNORMALITIES

• most frequent congenital anomalies (1:1000 newborns),

often occurring with other anomalies.

• play a role : environmental & genetic factors

CHEILOSCHISIS (CLEFT LIP)

• disorder during the fusioning of the maxillary process with theprolabium (both globular processes of the medial nasolateralprocess).

• can occur unilaterally or bilaterally

• 1=Eye anlage2=Ear anlage3=Nasal sac

• The arrows point to the locations of the missing epithelial bridges between the globular and maxillary processes that lead to a unilateral or bilateral cleft lip.

CHEILOGNATHOSCHISIS (CLEFT LIP AND JAW)

• besides the soft tissue fusion disorder of the upper lip,

the fusing of the lateral edges of the primary palate with

the two anterior edges of the secondary palate is also

disturbed.

• can occur unilaterally or bilaterally.

CHEILOGNATHOPALATOSCHISIS (CLEFT LIP, JAW AND PALATE)

• fusion disorder of the left and right portions of the secondary palatine lamina.

• it is not possible for an infant to suck and thereby take in nourishment, a surgical separation between the nasal and oral cavities must be undertaken as quickly as possible.

• 1=Fusion locations between maxillaryand globular processes of themedial nasal lamina

2=Fusion locations between theprimary and secondary palates

3=Fusion locations between the

two palatal processes

• In all cleft face and lip abnormalities fusion disorders occur, i.e., no epithelial bridges are formed.

FACIAL CLEFT

• disorders that affect the whole face seldom.

• oblique facial cleft deficient fusion of the epithelium of the lacrimonasal duct a fissure runs from the lower lid edge to the lower edge of the nasal opening.

• unilaterally or bilaterally or combined with a cleft lip-jaw-palate.

• 1=Eye2=Ear anlage3=Nasal sac

no epithelial bridges

have been formed.

FACIAL CLEFT

• middle cleft face disorder of the bringing to the front of

the nose and eyes, no flattening of the medial facial

furrows occurs, e.g., between the two globular processes

• comes from an inhibition of tissue proliferation in this

region

• 1=Eye

2=Ear anlage

3=Nasal sac

FACIAL CLEFT

• transversal cleft face disorder of cheek formation and

a survival of the early, primitive oral fissure (macrostomia)

that extends into the anlage region of the ears (between

the 1st and 2nd pharyngeal arches).

• 1=Eye

2=Ear anlage

3=Nasal sac

PATHOLOGY OF THE HEADGUT

• In the region headgut abnormalities pharyngeal arches,

clefts and pouches

• Connected with the pharyngeal arches are hypoplasias in the

region of the first mandibular arch. Cysts and fistulas result

from persisting pharyngeal pouches (among others). Ectopic

glandular tissue of the thyroid, of the thymus or the

parathyroids can be explained by remaining tissue residuals

along their descent.

• Abnormalities can also result from disorders of the migration

or development of neural crest tissue in this region.

CERVICAL FISTULAS, CYSTS AND SINUS

• This group of abnormalities derived from persisting pharyngeal pouchesor longitudinal cervical grooves.

Cysts closed cavities with an epithelial lining.Sinusescavities that remain open towards the outside or towards the pharynx and

fistulas connections between the pharynx and outer surface of the neck.

• 1=Sternocleidomastoid muscle

• Frequent locations for lateral

cervical cysts, sinuses and fistulas.

Roman numbers corresponding

pharyngeal groove.

PIERRE ROBIN SYNDROME (PRS)

• combines extreme micrognathia, cleft palate and

abnormalities of the ears

• relative macroglossia (in relation to a very small lower

jaw) is present the tongue fall backwards into the

throat air passage constrictions

PERSISTING THYREOGLOSSAL DUCT

• Ectopic thyroid tissue can be found along descent of the thyroid gland from the foramen cecum to the isthmus of the normal thyroid below the larynx.

• 1=Tongue2=Foramen cecum3=Epiglottis4=Hyoid cartilage5=Thyroid cartilage6=Thyroid gland7=Thyreoglossal duct

CATCH 22 SYNDROME

• The CATCH 22 syndrome = a developmental defect of the 3rd and 4th pharyngeal pouches.

• The symptoms :

• hypo- or aplasia of the thymus with defective T-cells and weak immunity

• hypoplasia of the parathyroid with hypocalcaemia and tetaniccramps

• cardiac defects (predominately conotruncal defects)

• facial dysmorphisms (hypertelorism; short lid axes; epicanthus; wide, short nose with everted nasal base levels; short philtrum; small, pointed mouth; microretrogenia; low-placed, dysmorphic ears with enlarged anteroposterior diameter).

CATCH 22 SYNDROME

• Genetics:• Most represent sporadic but there are also families, corresponding to

a dominant inheritance pattern with variable expressivity.

• The main cause microdeletion 22q11 (partial monosomy 22q11) that can be detected in around 95% of the affected children.

• Other chromosomal disorders or a teratogenic genesis (maternal diabetes mellitus, alcohol abuse, retinoids) have also been described.

• 15 - 20% of the affected have inherited the microdeletion 22q11 from a healthy parent. This healthy deletion carrier frequently has facial microsymptoms associated with the monosomy 22q11.

• Frequency:Entire population: CATCH 22 syndrome: 1/20000Entire population: Partial monosomy 22q11: 1/5000

MISSING DESCENT OF THE PHARYNGEAL POUCH DERIVATES

• migration parathyroid and thymus during their

development tissue remnants can also remain and

survive at ectopic locations

• do not give rise to functional disorders

PATHOLOGY OF THE FOREGUT

• in the lower foregut

region fistulas, stenosis and ectopic tissue also

form the main class of the abnormalities.

ABNORMALITIES IN THE ESOPHAGUS REGION

• Most frequent Fistulas or atresias of esophagus ≈ abnormalities developing respiratory tract.

• A=Atresia of the esophagus with abeginning fistulaB=Atresia of the esophagusC=Atresia of the esophagus withfistula of the lower esophagus -a section to the tracheaD=Atresia of the esophagus withfistula of the upper esophagus-a section to the trachea1=Trachea2=Esophagus

• Seldom stenosis of the esophagus result

from a missing recanalization during development.

• Atresias or stenosis of the esophagus fetus cannot swallow and reabsorb amniotic fluid, leading to a polyhydramnion.

PYLORIC STENOSIS

• = hyperplasia of the pyloric sphincter muscle leads to

sudden and convulsive vomiting, can be rectified by

a longitudinal incision of the pyloric sphincter

muscle.

• relatively frequent, mainly in male newborns.

DUODENAL STENOSIS

• based on an absent recanalization of the lumen.

• very seldom.

PATHOLOGY OF THE MIDGUT

• Disorders due to the large changes in shape during

the embryonic period in this region

MECKEL'S DIVERTICULUM

• 2-4% of the population exhibits Meckel'sdiverticulum.

• a sac with a dead end that lies ca. 50 cm cranial to the iliocecal valve and represents the remnant of the omphalomesentericduct

• usually it is discovered accidentally but can become infected or exhibit ectopic tissue.

OMPHALOCELE

• omphalocele intestinal loops remain in the umbilical coelom and are not repositioned into the abdominal cavity, coated with amnionand peritoneum.

• In an omphalocele intestinal

loops are visible outside the

body and skin and musculature

are absent

• DD/ with umbilical hernia = a weak abdominal musculature that is not able to hold back the intraperitoneal contents of the abdominal cavity

• umbilical hernia is always covered with skin.

MALROTATION AND COECAL ELEVATION

• Sometimes, when the intestinal loops return back into

the abdominal cavity, no or an incomplete

rotation occurs

• can remain asymptomatic or lead to a volvulus or other

form of strangulation.

ATRESIAS

• incomplete recanalization of the intestinal lumen can

also occur in the other regions of the intestines after the

first trimester of the pregnancy.

AGANGLIONIC MEGACOLON (HIRSCHSPRUNG'S DISEASE)

• frequency = 1:5000, boys >>

• Hirschsprung's disease ( congenital megacolon) = a congenital defect of ganglion cells in the large intestine.

• In a certain portion of the large intestine (thinner in this region and cannot expand very far) nerve cells are absent that normally stimulate the muscles to contract and transport the intestinal content. Both Auerbach's and Meissner's plexus are affected.

• Stools remains at this location congenital megacolon.

• frequent accompaniment : absent relaxation of the anal sphincter muscle

• Characteristic : the abdomens are bloated and hard – they suffer from vomiting and constipation

• Therapy = a surgical removal

PATHOLOGY OF THE HINDGUT

• embryonic hindgut begins already in the transition from

the middle to the last third of the transverse colon, blood

supply by the superior mesenteric artery ceases and

blood supply of the inferior mesenteric artery begins.

• only the abnormalities of the anus will be mentioned

here.

MISSING PERFORATION OF THE ANUS, ANAL ATRESIA, FISTULAS

• The development of the anus can be disturbed in a large number of ways. The disorder ranges from a simple membrane at the anal exit (persisting cloacalmembrane) to atresias of various lengths. Every newborn, therefore, must be examined to see whether the anus is open. Sometimes the anal atresia is combined with a fistula, which connects the intestine with another structure of the original urogenital sinus. Frequently fistulas form that extend as far as the vagina, theurethra, the bladder or into the perianal region on the outside.

LIVER ABNORMALITIESATRESIAS OF THE BILE PASSAGES

• Many shape variations of the liver and the discharging bile passages exist but most of them have no functional importance.

• One serious abnormality is an atresia of the bile passages. This disorder can occur at any place along the bile passage, from the tiny canaliculi to the discharging bile duct. Newborns with an atresia of the bile passages develop an icterus shortly after birth. When the cause cannot be corrected, a liver transplantation is necessary.

PANCREAS ABNORMALITIES

• Pancreas abnormalities can affect only its form but also

its function. Form variations are relatively frequent

without there being any influence on function

ANNULAR PANCREAS

• very seldom, frequently associated with the Down

syndrome

• pancreas forms a ring around the whole duodenum..

CYSTIC FIBROSIS (CF)

• Cystic fibrosis(mucoviscidosis) is the second most

frequent hereditary disease.

• The outflow passages of the exocrine portion of the

pancreas become stopped up due to the viscous mucus

buildup of secretion fibrous tissue throughout the

organ pancreas insufficiency.

CYSTIC FIBROSIS (CF)

• CF = a congenital, autosomal recessive, inherited, multi-organ syndrome caused by a deficiency

of CFTR (cystic fibrosis transmembrane regulator), a regulatory protein of chloride transport

through the cellular membrane with consecutive elevation of the viscosity of bodily secretions.

• The defective enzyme on chromosome 7 influencing of the active chloride transport, primarily

from epithelial cells.

• The most severe sequelae : pulmonary (chronic bronchitis) and intestinal.

• Gastrointestinal manifestations meconiumileus, pancreas

insufficiency, maldigestion, prolapse of the rectum, cholestasis, prolonged

icterus,cholestatic hepatic cirrhosis.

• Death before the 1st year of life is almost exclusively due to intestinal complications, later as

the result of pulmonary affection together with heart failure due to the overload of lung

circulation. Life expectancy amounts to 25 - 35 years.

• Diagnosis : Elevated osmolality and elevated NaCl content in sweat.

• only symptomatic treatment available retaining the longest possible organ functions.

At various clinics a sweat test is now performed routinely as a part of newborn screening.

Maternal

Consumption of

Coffee and

Caffeine-containing

Beverages

and Oral Clefts:

A Population-based

Case-Control Study

in Norway

DISCUSSION FROM ARTICLE : A METABONOMICAPPROACH TO ANALYZE THE DEXAMETHASONE-

INDUCED CLEFT PALATE IN MICE

• In the normal mouse embryo, palate shelves grow and elevate into a horizontal position by embryonic day 14 (E14)

• By the day of E17, the process of fusion has completely finished.

• Some studies incidence of cleft palate may be closely related to high maternal concentration ofplasma homocysteine OR lower activity of the glucocorticoids prereceptor metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β2HSD2) in placental trophoblastic cells.

DAFTAR PUSTAKA

• Embyology.ch

• Article : A Metabonomic Approach to Analyze the

Dexamethasone-Induced Cleft Palate in Mice

• Jornal : Maternal Consumption of Coffee and

Caffeine-containing Beverages and Oral Clefts: A

Population-based Case-Control Study in Norway