DR.ADHITA DWI ARYANTI,.M.KES
• 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 the
prolabium (both globular processes of the medial nasolateral
• can occur unilaterally or bilaterally
• 1=Eye anlage
• 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
• 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
• can occur unilaterally or bilaterally.
CHEILOGNATHOPALATOSCHISIS (CLEFT LIP, JAW
• fusion disorder of the left and right portions of the secondary
• 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 maxillary
and globular processes of the
medial nasal lamina
2=Fusion locations between the
primary 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.
• 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.
no epithelial bridges
have been formed.
• 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
• 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).
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
• This group of abnormalities derived from persisting pharyngeal
pouchesor longitudinal cervical grooves.
Cysts closed cavities with an epithelial lining.
Sinuses cavities that remain open towards the outside or towards
the pharynx and
fistulas connections between the pharynx and outer surface of the
• 1=Sternocleidomastoid muscle
• Frequent locations for lateral
cervical cysts, sinuses and fistulas.
Roman numbers corresponding
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
• 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.
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
• hypoplasia of the parathyroid with hypocalcaemia and tetanic
• 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
• 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
• 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.
Entire population: CATCH 22 syndrome: 1/20000
Entire population: Partial monosomy 22q11: 1/5000
MISSING DESCENT OF THE PHARYNGEAL POUCH
• 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
• Most frequent Fistulas or atresias of esophagus ≈ abnormalities developing respiratory
• A=Atresia of the esophagus with a
B=Atresia of the esophagus
C=Atresia of the esophagus with
fistula of the lower esophagus a section to the trachea
D=Atresia of the esophagus with
fistula of the upper esophagusa section to the trachea
• 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.
• = hyperplasia of the pyloric sphincter muscle leads to
sudden and convulsive vomiting, can be rectified by
a longitudinal incision of the pyloric sphincter
• relatively frequent, mainly in male newborns.
• 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
• 2-4% of the population
• a sac with a dead end that
lies ca. 50 cm cranial to
the iliocecal valve and
represents the remnant of
• usually it is discovered
accidentally but can become
infected or exhibit ectopic
• omphalocele intestinal loops remain in the umbilical coelom and are
not repositioned into the abdominal cavity, coated with amnion
• In an omphalocele intestinal
loops are visible outside the
body and skin and musculature
• DD/ with umbilical hernia = a weak abdominal musculature that is
not able to hold back the intraperitoneal contents of the abdominal
• umbilical hernia is always covered with skin.
MALROTATION AND COECAL
• Sometimes, when the intestinal loops return back into
the abdominal cavity, no or an incomplete
• can remain asymptomatic or lead to a volvulus or other
form of strangulation.
• incomplete recanalization of the intestinal lumen can
also occur in the other regions of the intestines after the
first trimester of the pregnancy.
• 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
• 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
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 cloacal
membrane) 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
ATRESIAS OF THE BILE PASSAGES
• Many shape variations of the liver and the discharging
bile passages exist but most of them have no functional
• 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 can affect only its form but also
its function. Form variations are relatively frequent
without there being any influence on function
• very seldom, frequently associated with the Down
• 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.
and Oral Clefts:
DISCUSSION FROM ARTICLE : A METABONOMIC
APPROACH TO ANALYZE THE DEXAMETHASONEINDUCED 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
• Some studies incidence of cleft palate may be
closely related to high maternal concentration of
plasma homocysteine OR lower activity of the
glucocorticoids prereceptor metabolizing enzyme
11β-hydroxysteroid dehydrogenase type 2
(11β2HSD2) in placental trophoblastic cells.
• 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