Download HIGH YIELD EMBRYOLOGY 2012

HIGH YIELD EMBRYOLOGY
EARLY EMBRYOLOGY
Teratogen
Capacitation
Dizygotic (fraternal) twins
Monozygotic (identical) twins
Human chorionic gonadotrophin (hCG)
Progesterone
Gastrulation
Notochord
Alpha-fetoprotein
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– substance affecting migration, proliferation or interaction of cells; an environmental
cause of congenital anomalies
– pruning of the sperm glycocalyx; permits the sperm-oocyte interaction
– arises from multiple ovulations (high levels of FSH)
– arise from splitting of a single zygote
– secreted by syncytiotrophoblast
– secreted by corpus luteum for five months, then by placenta; contraceptive “pill” and
RU-486 are anti-progesterones
– process where the epiblast gives rise to mesoderm, endoderm and ectoderm
– derives from both endoderm and mesoderm; forms the nucleus pulposus
– liver glycoprotein; leaks into amniotic fluid with neural tube or ventral wall defects
Most organ systems are susceptible to the effects of teratogens during the embryonic period; during the
fetal period the brain, eyes, ears, teeth, palate and external genitalia are susceptible.
Ectopic pregnancy – involves ~2% of all pregnancies and 95% occur in the uterine tubes
Placenta previa – implantation of the placenta over or near the internal os of the cervix
Placental abruption – placenta becomes disconnected from the uterine wall
Placenta accreta – the placenta adheres to the myometrium
Placenta percreta – penetrates the full thickness of the myometrium and fails to separate from the uterine
wall
Erythroblastosis Fetalis (Hemolytic disease of the newborn): occurs when there is a Rh incompatibility
between mother and fetus – mom has to be exposed to fetal blood (tramua, birth); mom makes antibodies
(IgG) against the fetal antigen and these antibodies can cross the placenta; if there is a future pregnancy
with a Rh incompatibility, these antibodies can cross the placenta and attack fetal red blood cells, causing
anemia and edema (fetal hydrops)
Hydatidiform mole - Occasionally the developing embryo dies and the chorionic villi fail to vascularize,
resulting in the formation of a cystic swelling of the uterus (hydatidiform mole). Hydatidiform moles can
reach various stages of development and typically produce excessive amounts of hCG. Complete moles
(90% are 46, XX) are essentially a placenta without an embryo and have only paternal chromosomes, have
high hCG, hypertension and bleeding. Complete hydatidiform moles present with vaginal bleeding,
hyperemesis, “uterine enlargement greater than expected for gestational age”, pre-eclampsia and theca
lutein cysts. Partial moles result from a poorly developed embryo and are always triploid (XXX, XXY or
XYY), usually develop by fertilization of an oocyte by two sperm and involve at least some fetal tissue.
Patients with partial moles will also have high hCG.
Holoprosencephaly
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results from the death of midline cells (alcohol)
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causes a deficiency of midline head structures
Situs inversus
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Complete – all organs are a mirror image of normal
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Incomplete – only a single organ is involved (e.g. heart)
Sirenomelia
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caudal dysgenesis resulting from inadequate mesoderm in caudal regions
limb defects, urogenital defects
Sacrococcygeal teratoma
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results from the persistence of the primitive streak and pluripotent cells
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1 in 37,000
Important chromosomal abnormalities:
 Trisomy 21, 18 and 23
 Klinefelters Syndrome
 Turner Syndrome
 Triple X
 Angelman Syndrome
 Prader-Willi Syndrome
Alpha-feto protein:
 Elevated in fetal body wall defects
 Decreased in maternal serum in trisomy 21 and 18
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MUSCULOSKELETAL
1. Congenital malformations of the vertebral column
 Scoliosis – abnormal curvature because of improper fusion or formation
 Variations in the number of vertabrae – there can be additions or subtractions in the number of
vertabrae
 Sternum – pes excavatum; cleft sternum
 Hemivertabrae – abnormal fusion resulting in misformed vertabrae
 Accessory ribs/Fused ribs  Spina bifida occulta – incomplete neural arc; usually asymptomatic and accompanied by a patch of hair
over the lesion
 Klippel-Feil syndrome – short neck from reduced number of cervical vertebrae
 Chordoma – remnants of the notochord may give rise to malignant tumors that invade bone; they
develop at the base of the skull and in the lumbar region
2. Congenital malformations of muscle
 Muscular dystrophies – conditions that result in weakness and muscle atrophy
 Accessory muscles – abnormal splitting of myotomes
 Poland anomaly – congenital absence of the pectoralis major
 Congenital torticollis – contracture or shortening of the sternocleidomastoid
3. Congenital malformations of bone
 Achondroplasia - the cause of dwarfism (1 in 15,000); limbs are bowed and short; results from a
disturbance of endochondral ossification at epiphyseal plates.
 Thanatophoric Dysplasia - a lethal skeletal dysplasia (1 in 20,000); infants die soon after death because
of respiratory failure; attributed to a fibroblast growth factor receptor deficiency
4. Congenital malformations of the limbs - limb defects are classified as either: amelia (absence of an entire
limb or meromelia (absence of part of a limb)
 Cleft Hand or Foot
· Lobster claw deformity – fusion of digital rays
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· Absence of central digits – fusion of digital rays
· Failure of digital rays to form – absence of digits
Floating Thumb: absence of the metacarpal bone in the thumb; phalanges are intact
Congenital Absence of Radius: the radius fails to form; hand deviates laterally
Finger Anomalies:
· Brachydactyly: the digits are relatively short; this is often associated with short stature.
· Polydactyly: supernumery digits – extra division of digital rays, the extra digit is usually useless
· Syndactyly: this defect occurs 1 in 2200 and is characterized by the fusion of the digital rays; can be
cutaneous (webbing of the digits) or osseous – fusion of bones.
· Macrodactyly: finger of adult size at birth; usually diminish with age
Congenital Clubfoot (Talipes): any defect involving the talus (1 in 1000), results from abnormal
orientation of the foot that prevents normal weight bearing.
Congenital Dislocation of Hip: results from laxity of the joint capsule or underdevelopment of the
acetabulum
Genu Recurvatum: congenital hyperextension of the knee; returns to normal alignment without
intervention
CENTRAL NERVOUS SYSTEM
A. Neural tube defects - improper closing of the neural tube, can be detected with amniocentesis (elevated
alpha fetoprotein); prevented by folate
1. Issues related to the caudal neuropore:
· Spina bifida occulta – involves only the vertebral arch, usually the only evidence is a small tuft of
hair over the lesion
· Spina bifida cystica – vertebral arch defect + a cyst like mass
 Meningocele – only meninges
 Meningomyelocele – involves some neural tissue (rootlets), meninges and CSF
 Spina bifida with myeloschisis - the neural folds fail to fuse posteriorly and the spinal cord is
open to the exterior
2. Issues related to the rostral neuropore:
· Meroanencephaly/Anencephaly - results from a failure of the anterior neuropore to close, the
brain tissue in this region undergoes degeneration; incompatible with life outside the uterus,
accompanied by elevated alpha-fetoprotein and polyhydramnios (the fetus lacks the control for
swallowing)
B. Spinal dural sinus – indicated by a dimple in the lumbar region; indicates the region of closure of the
caudal neuropore; can be connected through a fibrous cord to the dura mater
C. Tethered Cord Syndrome – defect in secondary neurulation; the conus medullaris and filum terminale are
abnormally fixed to vertebral column; associated with lower limb and bladder control problems
D. Hirschsprung’s Disease - occurs in 1 in 5000 live births, delayed passage of meconium; results in
constipation, vomiting, abdominal distension and rupture of the cecum; caused by the failure of the gut to
become invaded by neural crest cells; as a result this part of the gut is non-peristaltic
E. Craniopharyngiomas – arise from remnants of Rathke’s pouch; associated with diabetes insipidus and
visual deficits
F.
G.
H.
I.
J.
K.
L.
M.
N.
Schizencephaly – large clefts in cerebral hemispheres continuous with ventricles
Lissencephaly – decreased number of gyri, smooth surfaced cortex
Neuronal heterotopia - neurons in the wrong location, usually associated with ependyma
Arnold-Chiari malformation – herniation of cerebellum through an enlarged foramen magnum; associated
with spina bifida cystica
Dandy-Walker – enlarged posterior fossa, absent cerebellar vermis replaced by midline cyst
Agensis of the corpus callosum – associated with misshapen (bat-wing) lateral ventricles
Cranium bifidum - refers to a cranial defect in one of the thin bones of the skull, allows structures to
herniate out of the skull; levels of severity:
1. Meningocele – only meninges
2. Meningoencephalocele – meninges and brain tissue
3. Meningohydroencephalocele – meninges, brain and ventricle
Microcephaly - results from a defect in the growth and development of the CNS – the brain fails to grow;
the growth of the calvaria results from increased pressure caused by growth of the brain – so a small brain
ceases to stimulate growth of the skull beyond some base level, as a result these individuals experience
severe mental handicaps.
Hydrocephalus - results from impaired circulation or absorption of CSF, a congenital constriction of the
ventricular system can cause accumulation of CSF, dilation of the ventricles and compression of the
cerebral cortex; congenitally this occurs at the cerebral aqueduct.
RESPIRATORY SYSTEM
A. Atresia and Fistulas - esophageal atresia results from abnormal partitioning of the esophagus and trachea
and involves a narrowing or closure of the esophagus; can occur with or without a fistula; most
tracheoesophageal fistulas involve a proximal esophageal pouch and a distal esophagus that
communicates with the airway; associated with polyhydraminos.
B. Laryngotrachesophageal cleft: the larynx/trachea fail to completely separate from the esophagus;
distinguished from fistulas by aphonia
C. Tracheal diverticulum: a blind pouch projecting from the trachea
D. Lobe of the azygous vein: in 1% of people the azygos vein creates a deep groove along the apex of the
right superior lobe of the lung
E. Congenital lung cysts: formed from dilation of terminal bronchi, usually at the periphery of the lung; if
multiple cysts form the lungs will have a honeycomb appearance
F. Respiratory Distress Syndrome - results from insufficient surfactant, causing alveoli to collapse during
expiration. This is a common cause of death to premature infants. Tissue damage results in cellular and
serum proteins accumulating in the partially collapsed alveoli; further damage will result in detachment of
the alveolar lining  this is called HYALINE MEMBRANE DISEASE (the desquamated cells look like hyaline
cartilage). This can be addressed with surfactant replacement therapy and glucocorticoids to stimulate
surfactant production.
G. Ectopic Lung Tissue - results from lobes of lung tissue arising from the trachea or esophagus.
H. Hypoplasia – associated with congenital diaphragmatic hernias; characterized by reduced lung volume and
hypertrophy of the smooth muscle in pulmonary arteries; pulmonary hypertension leads to decreased
blood flow through the lung [blood is shunted through a PDA]
I. Accessory Lung: extra lung tissue, found usually along the base of the left lung but does not receive
pulmonary vessels (instead gets systemic circulation)
J. VACTERL association
Esophageal atresia and Tracheoesophageal fistulas are commonly associated with other birth defects.
Often cranial malformations are associated with caudal malformations:
V – vertebral defects
A – anal atresia
C – cardiovascular anomalies
T E – tracheoesophageal fistula
R – renal defects, radial forearm anomalies
L – limb defects
CARDIOVASCULAR
1.
2.
3.
4.
Dextrocardia: right-sided heart; situs inversus involves all organs in the body cavity
Ectopia cordis: ventral wall defect where the heart is on the outside of the thorax
Sudden infant death syndrome: possibly caused by abnormalities in the cardiac conducting system?
Atrial septal defects (ASD) - can involve a persistent ostium secundum; common atrium; defect in the
endocardial cushions and sinus venosum, probe patencies have an incidence of ~10%
5. Ventricular septal defect - typically involves the membranous portion of the septum; the clinical
consequences depend on the size of the defect: a large defect can cause left to right shunting of blood
while a small defect may close spontaneously
6. Cor triloculare biventriculare – absence of a atrial septum resulting in a three chambered heart
7. Premature closure of the oval foramen – leads to hypertrophy of the right atrium and ventricle and
hypotrophy of the left chambers; patient typically dies shortly after birth
8. Transposition of the great vessels - the septum that normally divides the aorta and pulmonary trunk does
not form properly
9. Pulmonary valve stenosis/Atresia:
10. Tricuspid valve stenosis/Atresia:
11. Ebstein anomaly: improper formation of the tricuspid valve where the valves are partially fused to the
ventricular wall; part of the right ventricle becomes “atrialized”; accompanied by tricuspid regurgitation;
indicated by cyanosis and heart failure; usually accompanied by a ASD
12. Hypoplastic left heart syndrome: poorly developed left ventricle; as blood returns from the lungs it must
pass through an ASD to the right atrium, into the right ventricle and then through a patent ductus
arterious into the systemic circulation; without surgical correction this condition is fatal
13. Tetralogy of Fallot – a group of four cardiac defects:
1. pulmonary stenosis
2. ventricular septal defect
3. right ventricular hypertrophy
4. dextroposition of the aorta – aorta gets blood from the right ventricle
14. Persistent truncus arteriosus
 conotruncal ridges do not fuse
 accompanied by IV septal defect
 the truncus gets blood from both ventricles
15. Aortic Valvular atresia / stenosis
16. Patent ductus arteriosus – 2x more common in males; associated with rubella infection/birth at high
altitude; continuous machine-like murmur in the upper left sternal border
17. Coarctation of the aorta – characterized by a constriction of the aorta, most are directly opposite the
ductus arteriosus
a. post-ductal – adult; constriction is distal to DA
b. pre-ductal – infantile; constriction is proximal to DA
c. with PDA – cyanosis in lower extremities; usually require surgical intervention
d. without PDA – weak pulses in lower extremity, rib-notching; may be asymptomatic
18. Abnormal origin of the right subclavian artery
19. Double inferior vena cava – persistence of left supracardinal vein, may be mistaken for enlarged lumbar
lymph nodes; pulmonary embolism after insertion of an IVC filter
GASTROINTESTINAL
1. Congenital Diaphragmatic Hernia (Hernia of Bochdalek) - a common malformation of the newborn
(1/2000), results from failure of the pleuroperitoneal membrane to close the pericardioperitoneal canal,
most common (85-90%) on the left – left canal is larger and closes later, has a high rate of mortality
because of pulmonary dysfunction.
2. Esophageal Hernia (Hiatal) - common; due to a defect in the right crus and/or short esophagus, the
stomach is constricted at the level of the diaphragm or may herniate into thorax
3. Parasternal Hernia - uncommon; results from a deficit between the sternal and costal heads of the
diaphragm, may go undetected until the child is several years old
4. Esophageal atresia - Atresia – results from deviation of the tracheoesophageal septum so there is
incomplete separation of the esophagus and trachea; associated with polyhydraminos
a. achalasia – lack of ganglion cells  tonically contracted = dysphagia
5. Congenital hypertrophic pyloric stenosis – thickening of the pylorus, results in obstruction and the
stomach becomes distended; associated with projectile vomiting
6. Duodenal stenosis – usually results in bile containing vomit
7. Duodendal atresia – vomiting begins a few hours after birth, contains bile with distention of the
epigastrium (double bubble sign)
8. Accessory hepatic ducts – variations in the hepatic ducts are common
9. Extrahepatic biliary atresia – most common form is atresia of the bile ducts; jaundice occurs shortly after
birth and stool is “clay-colored” and urine is dark
10. Pancreas
a. Accessory pancreatic tissue – located in the wall of the stomach or Meckel’s diverticulum (see below)
b. Annular pancreas - ventral pancreatic bud encircles and constricts the duodenum; males more
commonly affected than females
11. Omphalocele - failure of the midgut to return to the abdominal cavity after physiological herniation;
covered by the amnion
12. Umbilical hernia – the protruding mass is covered by subcutaneous tissue and skin
13. Gastroschisis (Congenital Umbilical Hernia) - intestines herniate into umbilical cord after returning to the
abdominal cavity, involves a rupture of the amnion
14. Meckel’s Diverticulum (~1/100) - results from a persistence of the vitelline duct; produces acid 
ulceration and bleeding!
 RULE OF 2’s:
 affects 2% of population
 found 2 feet from iliocecal valve
 typically about 2 inches long
 contains 2 types of ectopic tissue (stomach and pancreas)
 age of presentation is typically 2 years of age
 males are 2X more likely to be affected
15. Malrotation – the gut rotates the wrong way; the cecum ends up on the left side
16. Mobile cecum – cecum has a mesentery and is mobile, can form volvulus
17. Hirschsprung’s Disease - failure of neural crest cells to migrate to the caudal 1/3 of the large intestine,
results in the absence of parasympathetic ganglia
18. Fistulas – involves improper formation of urorectal septum; rectovaginal; rectourethral
19. Hindgut
c. Imperforate anus – persistence of anal membrane
d. Anal stenosis
20. Atresia
 interruption of the gut tube
 symptoms include vomiting:
-esophagus - milk not curdled
-gastric - milk curdled
-duodenum - bile
URINARY
1. Wilm’s tumor – congenital tumor of the kidney
2. WAGR syndrome
 W – Wilm’s tumor
 A – aniridia
 G – genitourinary/gonadoblastoma
 R – mental retardation
3. Accessory renal arteries – common; resulting from the ascent of the kidney; can obstruct a ureter and
cause hydronephrosis
4. Polycystic Kidney - numerous cysts form on the kidney, genetic in origin; the kidney become very large and
renal failure occurs, requires kidney transplant for survival
5. Renal Agenesis - occurs when the ureteric bud fails to reach the metanephric mesoderm; associated with
oligohydramnios; bilateral = incompatible with life
6. Pelvic Kidney - As the kidney ascends towards the abdomen, they pass between the two umbilical arteries.
Occasionally, one gets blocked and remains in the pelvic cavity. This is a rare disorder (1/3,000).
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Fused kidney:
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Pancake kidney:
7. Horseshoe Kidney - during development the metanephric mesoderm fuses while in the pelvis, normal
ascent is stopped by the inferior mesenteric artery.
8. Bifid Ureter: occurs when the ureteric bud divides prematurely. This is a fairly common disorder and the
severity varies considerably.
9. Ectopic ureter - an ectopic ureter opens anywhere except into the urinary bladder (commonly into more
inferior parts of the urinary tract – urethra).
10. Megaloureter: enlarged ureter with no motility; prone to infection
11. Postcaval ureter: right ureter passes behind the IVC; can be obstructed
12. Obstructive genitourinary defect: stenosis or atresia of the urinary tract at any level
13. Exstrophy of the Bladder - a ventral body wall defect where the mucosa of the bladder is exposed to the
exterior, may be caused by the lack of mesodermal migration into the region between the genital tubercle
and the umbilicus
14. Urachal Fistula - the lumen of the allantois does not close; there is an abnormal communication of the
bladder to the outside via the anterior abdominal wall
15. Urachal Cyst - only a portion of the allantois remains; no communication from the bladder to the outside
16. Urachal sinus – the urachus remains open through the umbilicus, but looses its connection to the bladder
REPRODUCTIVE
Derivatives of the genital ducts:
· male – high level of testosterone stimulates development of the mesonephric duct; Mullerian inhibiting factor prevents
development of paramesonephric ducts
· female – low level of testosterone prevents development of mesonephric ducts and no Mullerian inhibiting factor permits
development of the paramesonephric ducts
· The mesonephric ducts form:
- male: epididymis, ductus deferens, seminal vesicle and ejaculatory duct
- female: epoophoron, paroophoron, Gartner’s duct [Gartner’s cyst]
· The paramesonephric ducts form:
- male: appendix of testes and prostatic utricle
- female: uterine tube, uterus and superior part of vagina
External Genitalia:
– after week 9 the genitalia can be distinguished as male or female!
MALE
FEMALE
UG folds
floor of urethra
labia minora
Genital swellings scrotum
labia majora
Genital tubercle penis
clitoris
UG sinus
urethra/prostate urethra/vagina
1. Turner’s Syndrome - Chromosomal anomaly (45, XO); Germ cells degenerate after reaching gonadal ridge;
ovaries do not form, but rather ovarian “streaks”; Genitalia are female but infantile
2. Hermaphrodites - a discrepancy between the morphology of the gonads and the appearance of the
external genitalia.
True hermaphrodite - true hermaphrodites are extremely rare and 70% of them have a 46, XX
chromosomal make-up. Most are raised as females and have both testicular and ovarian tissue or
an ovotestis. The phenotype may be male or female but the external genitalia are ambiguous.
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Male hermaphrodite - these individuals have a 46, XY genetic make-up. The internal and external
morphology varies and depends on the development of the paramesonephric ducts. The defects
are caused by inadequate production of testosterone and Mullerian Inhibiting Hormone (MIF).
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Female hermaphrodite - these individuals have a 46, XX genetic make-up and results from the
exposure of a female fetus to excessive levels of androgens. The most common effects are
masculinization of the external genitalia (enlargement of the clitoris and fusion of the labia). The
most common cause is congenital adrenal hyperplasia.
3. Klinefelter Syndrome - 47, XXY and therefore male, but have small testes, tall stature with long lower
limbs and gynecomastia; intelligence will often be effected.
4. Androgen Insensitivity Syndrome (also called Testicular Feminization Syndrome) - an extremely rare
condition (1 in 20,000 live births), patients are 46, XY but appear as normal females, the vagina ends in a
blind pouch and the uterine tubes are absent or rudimentary, the testes are usually located in the
abdomen or lodged in the inguinal canal; results from a resistance to the action of testosterone because of
a defect in the androgen receptor.
5. Hydrocele – processus vaginalis doesn’t close and accumulates fluid, usually spontaneously closes in a few
days
6. Cryptorchidism – undescended testes
7. Congenital INDIRECT inguinal hernia – intestinal loops protrude through a persistent processus vaginalis
(through the inguinal canal)
8. Uterine / Vaginal Abnormalities:
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Double uterus (uterus didelphys):
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Bicornate uterus
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Unicornate uterus
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Vaginal atresia:
9. Hypospadias – external urethral opening is on the ventral aspect of the penis
10. Epispadias – external urethral opening is on the dorsal aspect of the penis
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HEAD AND NECK
Pharyngeal Apparatus
Clefts (Grooves) – four pairs; ectoderm that forms only epithelium
The first cleft gives rise to the external auditory meatus.
The second through fourth clefts typically regress, but may persist and give rise to a cervical sinus.
Pouches – four pairs; endoderm that forms only epithelium
The first pouch gives rise to the auditory tube, mastoid antrum and tympanic cavity.
The second pouch forms the palatine tonsil.
The third pouch gives rise to the thymus and inferior parathyroid gland.
The fourth pouch gives rise to the superior parathyroid
Pharyngeal Arches – There are five pharyngeal arches; mesoderm forms skeletal muscle; neural crest grows into each arch and
forms all connective tissue (cartilage, bone and blood vessels)
Derivatives of the Pharyngeal Arches
First
Second
Third
Fourth
Sixth
Nerve
CN V3
muscles of mastication,
anterior belly of
digastric, mylohyoid,
tensor tympani and
Muscles
tensor veli palatini
maxillary
Artery
malleus and incus
Cartilage
CN VII
facial
muscles,
stapedius,
posterior
belly of
digastric and
stylohyoid
hyoid and
stapedial
CN IX
CN X
CN X
stylopharyngeus muscles of palate, muscles of larynx,
pharynx and
inferior
cricothyroid
constrictor,
cricopharyngeus
and superior
portion of
esophagus
common and
internal carotid
left: portion of
arch; right: part
one of subclavian
Pulmonary trunk
(left - ductus
arteriosus)
stapes, styloid greater horn and laryngeal cartilage laryngeal cartilage
process,
inferior portion of
lesser horn
body of hyoid
and superior
portion of
body of hyoid
1. Branchial Cysts/Fistula – results from persistence of the pharyngeal grooves; branchial fistulas occur when
the second arch fails to grow over the third and fourth arches. Such a defect results in the formation of a
lateral cervical cyst; fistulas have an external opening on the lateral aspect of the neck
2. Branchial Vestiges – normally pharyngeal cartilages disappear; remnants of cartilage or bony elements
under the skin anterior to the inferior 1/3 of the sternocleidomastoid persist
3. Ectopic Thyroid Tissue - The thyroid gland undergoes a migration from the oral cavity to the neck region.
It is common for remnants of thyroid tissue to remain along the course of migration. The parathyroids also
undergo a migration and are highly variable in their location.
4. Thyroglossal Cysts and Sinuses - thyroglossal cysts lie in the midline of the neck and are a tubular remnant
of the thyroglossal duct.
5. Ectopic parathyroids:
6. Neural Crest - Neural crest cells are important for the development of the pharyngeal arches. Facial
defects, resulting from deficient neural crest cells, are also accompanied by what other defects?
a. Treacher Collins Syndrome
 genetic defect involving the first arch
 variable; may have any of the following: hypoplasia of the mandible, face; malformation of ears,
eyelid defects, and faulty dentition
b. Pierre Robin Sequence
 involves first arch
 micrognathia
 cleft palate
 external ear defects
c. DiGeorge Anomaly – Involves abnormalities of the heart, parathyroid gland, face, and thymus gland
(the degree to which the immune system is affected varies). Affected individuals will have congenital
heart disease, unusual facial features with low-set ears, a small jawbone that recedes, wide-set eyes
and are born without parathyroid glands.
7. Acrania – no calvaria, failure of neural tube to close
8. Craniosyntosis – premature closure of the sutures, results in a skull with peculiar shapes:
Scaphocephaly – sagittal suture closes, skull is long and narrow
Oxycephaly – coronal suture closes, skull become tall
Plagiocephaly – asymmetric closure, the skull become twisted
9. Microcephaly – fontanelles close early and sutures close during the first year; a CNS defect whereby the
brain and calvaria fail to grow; accompanied by severe mental retardation
10. Choanal atresia: nasal cavity is not continuous with the pharynx, blocked by nasal epithelium (persistent
buccopharyngeal membrane?); part of the CHARGE association:
 C = coloboma of the iris, choroid
 H = heart defect
 A = atresia of choanae
 R = retraded growth
 G = genitourinary anomaly
 E = ear defect
11. Microstomia – excessive merging of maxillary and mandibular prominences
12. Atresia of the nasolacrimal duct 13. “Clefts” - common defects; result in abnormal facial appearance and defective speech
a. anterior cleft
 cleft lip that may involve the alveolar part of the maxilla, anterior to the incisive foramen
 deficit of maxillary prominence and intermaxillary segment
b. posterior cleft
 involves the secondary palate and extends through the soft and hard palate
 defective development of the secondary palate
 mild cases involve only the uvula
c. cleft lip
 involves only the lip and may be bilateral; occurs in various degrees
 1 in 1000; 70% of cases are male
d. median cleft
 rare; failure of medial nasal prominences to merge and form intermaxillary segment
 characteristic of Mohr syndrome
e. median cleft of the lower lip
 rare; failure of mandibular prominence to fuse
f. oblique facial cleft
 from upper lip to medial margin of the orbit
14. Atresia of the external auditory meatus: blockage of the external canal
15. Congenital cholesteatoma: epidermoid tissue within the tympanic membrane
16. Congenital retinal detachment - recall that the two layers of the retina were separated by an intraretinal
space, normally, there is some degree of fusion between these two layers; if these layers fail to fuse during
development the defect is congenital, retinal detachment can occur following a blow to the eye in which
case fluid can accumulate and vision can be impaired
17. Coloboma - This defect involves an improper closing of the choroid fissure resulting in a gap in the iris or
iris and retina.
18. Cyclopia - This defect occurs when there is fusion of the eye in the midline. Cyclopia is indicated by a
single eye; synophthalmia is indicated when there is incomplete fusion of the eyes. Cyclopia results from a
defect involving midline structures and is accompanied by other defects and is incompatible with life.
Cyclopia is often accompanied by a midline proboscis that is situated superior to the fused eye.
19. Microphthalmia - indicated by a small, normal appearing eye or an eye that was arrested at some point
during normal development; may lack a lens
20. Anophthalmia - indicated by the congenital absence of eye tissue, can vary in severity – can involve only
the optic stalk or may involve development of the forebrain
21. Persistent pupillary membrane - the pupillary membrane normally covers the anterior surface of the lens
and disappears during development, this membrane may remain as strands of connective tissue spanning
the pupil, rarely will interfere with vision
22. Congenital glaucoma - glaucoma is any increase in the intraocular pressure, occurs congenitally when
there is a defect in the draining mechanism (scleral venous sinus), may arise in relation to a rubella
infection during pregnancy
23. Congenital cataract - any lens opacity present at birth; can be progressive so may not be identified at
birth; can be caused by infection (rubella, chicken pox, herpes) or genetic
24. Aniridia: absence of the iris; defect involving neuroectoderm and neural crest cells
25. Color of the iris: the iris is typically blue/gray in most newborns; definitive pigmentation is acquired by 810 months
26. Congenital aphakia – absence of the lens
27. Congenital ptosis – what could cause this?
28. Minor deformities of the external ear are common and often accompany other anomalies:
 Anotia: absence of an ear
 Microtia: small ear; absence of auricular hillocks
 The persistence of extra auricular hillocks is called auricular appendages
 Preauricular sinuses are small depressions located anterior to the auricle; results from abnormal
closure of the first pharyngeal groove
 Atresia of the external auditory meatus: blockage of the external canal
 Congenital cholesteatoma: epidermoid tissue within the tympanic membrane
 Congenital fixation of the stapes:
INTEGUMENT
1. Ichthyosis - results from excessive keratinization of the skin, whereby the skin appears as very dry and
scaly; a harlequin fetus has an extreme form of this disorder where the skin is abnormally thick and
cracked; they typically die within a week of birth; a collodion infant is covered in a thick membrane that
cracks and eventually is shed revealing normal skin
2. Angiomas - not true tumors but may appear as a mass within the skin, result from the persistence or
surplus of blood or lymphatic vessels; Nevus flammeus refers to a flat pink or red blotch that appears on
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the posterior aspect of the neck; a hemangioma (port wine stain) also appears red but is found on the
face.
Albinism - results when the melanocytes fail to produce melanin and the skin, hair and retina lack pigment
Supernumery nipples - extra nipples or even breast can form anywhere along the milk lines and are fairly
common (approximately 1% of the population)
Inverted nipples –
Congenital alopecia – absence of loss of hair
Hypertrichosis – excessive hairiness; localized hypertrichosis is associated with spinal bifida occulta
Amelogenesis Imperfecta - in this condition the enamel is improperly formed and is soft and friable and
the teeth are yellow or brown because of exposed dentin; dentinogenesis imperfecta is a common
condition where the odontoblasts fail to differentiate and dentin is not calcified
Discolored teeth - certain chemicals can be incorporated into the dentin during tooth development;
tetracycline administered during pregnancy can cause the teeth to become yellowish-brown; in
erythroblastosis fetalis there is free hemoglobin that can be incorporated into the enamel and cause a
black discoloration of teeth
Changes at Birth
umbilical arteries 
umbilical veins 
urachus 
foramen ovale 
ductus arteriosus 
ductus venosus 
paired medial umbilical ligaments
round ligament of liver
median umbilical ligament
fossa ovalis
ligamentum arteriosum
ligamentum venosum
Miscellaneous
Stem villi
Intervillous space
– form from trophoblast and somatic layer of extraembryonic mesoderm
– contains maternal blood