ABSTRACT
TYPES OF DISRUPTION AFFECTING MORPHOGENESIS OF FETUS/EMBRYO
●● Vascular, anoxia, infection, radiation, amniotic entanglement, teratogenic drugs
Teratogens
●● Androgens (clitoral hypertrophy and labial fusion)
limb reduction defects) ●● Warfarin (nose hypoplasia, stippling of
epiphysis) ●● Fetal alcohol syndrome (telecanthus, absent
philtrum and thin vermilion border of upper lip)
Vascular causes
Cutis verticis gyrate
●● Thrombosis of sinus venosus with necrosis of cerebral cortex and collapse of the skull
●● Thickening of the scalp with severe microcephaly
Gastroschisis
●● Due to the premature ablation or disruption of ophthalmomesenteric artery
Subclavian artery supply disruption
●● Poland sequence, Klippel-Feil syndrome, and Mobius defect
●● Sternocleidomastoid muscle and breast hypoplasia
Amniotic disruption
●● Streeter band: Constriction ring in the ankle due to amniotic disruption sequence
NOONAN SYNDROME
unknown cause ●● Shares some features of Turner syndrome
(cystic nuchal hygroma)
TWIN-TO-TWIN TRANSFUSION (TTT) SYNDROME
TWIN REVERSED ARTERIAL PERFUSION SEQUENCE (TRAPS)
ZELLWEGER SYNDROME
APERT SYNDROME
BRACHMANN-DE LANGE SYNDROME
●● Growth deficiency, profound mental retardation
NEUROFIBROMATOSIS
ROBERT SYNDROME (PSEUDOTHALIDOMIDE)
spread
OVERGROWTH SYNDROMES
●● Elejalde syndrome (fibroblasts complete the cycle in less than 63% of normal time)
●● Beckwith Wiedemann (sporadic 85%, AD 10%–15%)
●● PTEN mutations (Bannayan-Riley-Ruvalcaba/Cowden syndrome/Proteus syndrome)
Proteus syndrome
mal nevi, vascular malformations, and dysregulated adipose tissue
tumors ●● Children with increased body size and neo-
plasia; increased prevalence of tumors such as neuroblastoma, leukemia, Wilms tumor, astrocytoma, osteosarcoma
CRANIOFACIAL ANOMALIES
Anencephaly
●● Open neural tube defect in the cephalic region
●● Exposed mass of degenerating neural tissue in the skull floor
Rachischisis
●● Complete spina bifida; cleft through the entire spinal cord
●● Posterior neuropore of the neural tube fails to close by 27th day of gestation
Encephalocele
ric encephalocele
Frontonasal dysplasia
●● Median bony clefting of frontal or frontonasal region
Holoprosencephaly
●● Developmental field defect-impaired midline cleavage of the embryonic forebrain
●● Alobar type; prosencephalon fails to cleave sagittally into cerebral hemispheres, transversely into telencephalon and diencephalon and horizontally into olfactory tracts and bulbs
●● Face predicts the brain 80% of the time; cyclops, arrhinia, proboscis, ethmocephaly, cebocephaly (blind-ended single nostril nose)
Craniosynostosis
Plagiocephaly
Crouzon syndrome
●● AD, craniosynostosis, maxillary hypoplasia, proptosis, and shallow orbits
Apert syndrome
●● Craniosynostosis, mid-face hypoplasia, congenital deafness, symmetric syndactyly of hands and feet
Classic Pfeiffer syndrome
Thanatophoric dysplasia
●● Type 1 and 2 have a disproportionately large skull
Cleidocranial dysplasia
Branchial arch syndrome
●● Hemifacial microsomia: Affects oral, aural, and mandibular growth (mostly unilateral)
●● Goldenhar syndrome: Oculo-auriculo-vertebral syndrome, epidural dermoids
●● Treacher Collins syndrome: AD, bilateral zygomatic hypoplasia, down-slanting palpebral fissures, malformed ears, and micrognathia
either partially/totally outside thorax, due to abnormal development of septum transversum
●● Poland syndrome: Unilateral absence or hypoplasia of pectoralis major muscle. May be associated with hypoplasia of breast, nipple, hand, or digit of that side
●● Jeune thoracic dystrophy: Lethal in infancyvery long and narrow thorax with extreme pulmonary hypoplasia
●● Amastia (absence of breast), Athelia (absence of nipple), Hypomastia (small breast)
cause breast hypoplasia and fibrosis in children
●● Accessory breast (polymastia lies within the milk line)
●● Ectopic breast (polymastia lies outside the milk line)
●● Macromastia: Virginal breast hyperplasia. Mostly stromal proliferation but sometimes glandular also (unilateral or bilateral). Increased sensitivity of mammary
adipocytes, fibroblasts, and epithelial cells to estrogen/progesterone
●● Gynecomastia: Enlargement of breast in adolescent males. Klinefelter syndrome (47XXY). Induced by estrogen and treated by tamoxifen. Mastectomy if resistant
NORMAL EMBRYOLOGY
●● At 6 to 10 weeks of development; physiological intestinal herniation occurs in the umbilical cord, which regresses at the 10th week
●● At 5 to 8 weeks of development; omphalomesenteric duct/vitellointestinal/vitelline ducts normally get absorbed. If they fail to absorb then there is development of Meckel diverticulum. Complications include bleeding, perforation, peritonitis, bowel intussusception
●● Umbilical cord attaches at the region of umbilical ring
●● Right and left umbilical ligaments are obliterated bilateral umbilical arteries
●● Normally at 33 weeks right umbilical vein atrophies in the placenta
●● Round ligament is the obliterated umbilical vein
PATHOLOGICAL DISORDERS
Umbilical granuloma
●● Drains small amount of serous and serosanguinous fluid
Umbilical hernias
●● Direct: 5% of individuals have neither a round ligament nor umbilical fascia, closing the umbilical ring
●● Indirect: When round ligament fails to cover the ring and it is only covered by umbilical fascia. By 5 to 6 years of age the hernia is mostly reduced spontaneously
Omphalocele/Exomphalos
●● Viscera herniated into the umbilical cord through the umbilical ring
somy 18
●● Complication is peritonitis when amnion ruptures
Gastroschisis
●● Defect is lateral to the umbilical ring; both the umbilical ring and the cord are normal
●● Viscera are encased in a gelatinous mass (no sac)
●● Defect to the right of the umbilical cord, liver not herniated
omphalocele)
NORMAL EMBRYOLOGY
●● In males, internal inguinal ring closes after descent of testis in scrotum through processus vaginalis, during the seventh and the eighth months of gestation
●● Obliterated canal forms fibrous band while scrotal portion is lined by mesothelium
●● Fluid-filled tunica vaginalis lies around the anterior portion of testis
PATHOLOGICAL DISORDERS
Indirect congenital inguinal hernia
●● Failure of closure of processus vaginalis results in hernia (intestines and other viscera herniate)
●● Common in cryptorchidism and prematurity
Acquired indirect inguinal hernia
●● Failure of upper portion of processus vaginalis to close
●● Blind peritoneum lined sac (not lined by tunica vaginalis)
Littre hernia
Hydrocele
●● Failure of closure of only the lower end of processus vaginalis
Direct hernia
Meconium peritonitis
meconium leaks into scrotum and presents as hemiscrotal mass-meconium periorchitis (d/d neoplasm)
Cryptorchidism
●● Risk of malignancy and infertility remains even after orchiopexy
Appendix testis
●● Aka hydatid of Morgagni-vestige of the müllerian duct
atous and congested testicular stroma leading to hemorrhagic infarction later
●● Normal amnion fuses with chorionic plate by 12 weeks postconception
●● Failure of the amniotic membrane to fuse with chorion-strips of membrane floating within the amniotic cavity
LIMB BODY WALL DEFECT (LBWD)
encephalocele with facial defects, limb defects ●● Rupture leads to defect in the body stalk-
very short umbilical cord ●● Amnion and chorion are affected due to
vascular disruption ●● Traction by the short cord-scoliosis
ing can predispose
AMNION RUPTURE SEQUENCE (ARS)
amniotic band ●● Interference with normal development ●● Clefts in ARS do not follow normal lines of
closure, asymmetrical ●● Amniotic surface of placenta absent/
necrotic
BACK AND PERINEUM
Primary neurulation
●● Conversion of neural plate into a cylindrical tube (between second and fourth week after fertilization)
Secondary neurulation
neuropore forms beneath the epidermis ●● Open neural tube defects do not extend to
the caudal sacrum ●● Closed neural tube defects (tethered cords,
lipomas) common in the terminal sacral region
●● Caudal eminence is pluripotential and gives rise to teratomas
Hindgut derivatives
●● Descending colon, rectum, urinary bladder, urethra, and lower vagina
●● Cloaca (terminal part of hindgut) communicates with allantois via urachus
●● Urachus involutes after fifth month of fetal life and persists as medial umbilical ligament
●● Cloaca partitioned into rectum and urogenital sinus by urorectal septum (coronal sheet of mesoderm)
Rachischisis
●● Defect in the spinal column involving the posterior part of the vertebrae
Spina bifida occulta
●● Spinal cord defect, skin and subcutaneous tissue are intact
Spina bifida aperta
●● Spinal cord defect, absent skin and subcutaneous tissue
Spondylothoracic dysplasia
●● Dysplasia of the thoracic vertebra associated with fusion, branching, ectopia, or agenesis of adjacent ribs
Vertebral anal cardiac tracheoesophageal renal limb (VACTERL) association
●● Associated with maternal diabetes mellitus/ sporadic
●● Differential diagnosis with Fanconi anemia (AR, overlapping features, diagnosed by chromosomal breakage studies)
Neurenteric cysts or fistulae
●● Rare congenital cysts, in contact with central nervous system (CNS), lined by gastrointestinal/respiratory mucosa
out mass effect ●● Lower cervical, thoracic, or thoracolumbar ●● Associated anomalies; dermal sinuses,
intradermal lipomas, tight filum terminale
Persistent cloaca
urinary bladder, vagina, and rectum ●● Results from incomplete septation of
embryonic cloaca by urogenital septum ●● Association with talipes, scoliosis, and
other deformities (intrauterine constraint perhaps from amnion involvement)
●● Males: Ambiguous genitalia associated. Mostly a fistulous connection between bladder and rectum with imperforate anus
●● Females: Bladder, vagina, and rectum all open into one common opening
nar, and glandular structures ●● Exstrophy-epispadias complex ●● Patients with exstrophy may later develop
neoplasia like adenocarcinoma and squamous cell carcinoma
Cloacal exstrophy
absent ●● Omphalocele, exstrophy, imperforate anus,
spinal anomaly
Urachal anomalies
●● Urachal cyst: Lined by transitional/cuboidal epithelium (versus vitelline remnants lined by intestinal epithelium)
●● Persistent urachus: Urine through the umbilicus
Anorectal abnormalities
Prune-belly syndrome
●● Triad of congenitally deficient abdominal musculature, urinary tract anomaly, and cryptorchidism in males
Caudal dysgenesis
●● Caudal duplication (duplication of the pelvic organs, sacrum)
●● Caudal dysplasia (sacral dysgenesisdysplasia, hypoplasia, or absence of sacral vertebrae)
Currarino syndrome
●● Partial sacral agenesis, presacral tumor (anterior meningocele, enteric cyst, presacral teratoma) and anorectal malformation
Sacral dysgenesis with lower extremity anomalies-Sirenomelia
●● Associated with maternal diabetes mellitus
●● Renal agenesis with imperforate anus and malformed external genitalia
●● Single umbilical artery arising from abdominal aorta
●● CNS: Microcephaly, anencephaly, holoprosencephaly
defect, transposition of great vessels, situs inversus, single umbilical artery
●● Gastrointestinal tract: Malrotation of bowel, anal/rectal atresia
●● Genitourinary: Renal agenesis, hypospadias, cryptorchidism, multicystic dysplasia
●● Skeletal: Caudal agenesis, rib and/or vertebral anomalies
●● Hyperinsulinemia, hyperglycemia, and macrosomia
