Fetopathology and developmental pathology of the embryo and fetus
Marta Ježová, Josef Feit et al.
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+ Atlas of fetal pathology
+ Congenital malformations
+ Physiological developement of an embryo and fetus, growth and changes of the external shape
+ Congenital malformations and congenital anomalies
+ Basic terminology
+ Etiology of congenital anomalies (CA)
+ Environmental causes of congenital anomalies, congenital infections
+ Rubella
+ Cytomegalovirus
+ Syphilis
+ Toxoplasmosis
+ Diabetes mellitus (DM) and pregnancy
+ Diabetic embryopathy
+ Diabetic fetopathy
+ Genetic causes of congenital malformations
+ Chromosomal abnormalities
+ Down syndrome
+ Klinefelter syndrome
+ Turner syndrome
+ Patau syndrome
+ Edwards syndrome
+ Triploidy
+ Single gene disorders
+ Tuberous sclerosis
+ Miscellaneous malformation syndromes, sequences and associations, unclassified
+ Sirenomelia (Mermaid syndrome)
+ Hydrops fetalis
+ Immune hydrops (erythroblastosis fetalis, hemolytic disease of the newborn)
+ Nonimmune hydrops
+ Hygroma colli cysticum
+ Pierre-Robin sequence
+ Caudal regression syndrome (sacral agenesis)
+ VACTERL association
+ Pathology of twinning
+ Complications of monochorionic diamnionic placentation
+ Chronic twin transfusion syndrome
+ Acute twin-twin transfusion
+ Complications of monochorionic monoamnionic placentation
+ Congenital malformations in twins
+ Chorangiopagus parasiticus (acardius)
+ Pathology of higher multiple gestations: triplets
+ Monsters
+ Monstra duplicia
+ Gemini monochoriati inequales
+ Duplicitas symmetros
+ Asymmetric dual monsters
+ Monstra simplicia
+ Congenital malformations of individual organ systems
+ Congenital malformations of the central nervous system
+ Congenital malformations of the spinal cord
+ Spina bifida
+ Myeloschisis (rachischisis posterior)
+ Congenital malformations of the brain
+ Anencephaly
+ Iniencephaly
+ Encephalocele
+ Arnold-Chiari malformation
+ Disorders of formation of the structures derived from the mediobasal prosencephalon
+ Migration disorders
+ Destructive lesions of fetal brain (disruptions)
+ Porencephaly
+ Hydranencephaly
+ Hydrocephalus
+ Dandy-Walker malformation
+ Intracranial non-neoplastic cysts
+ Arachnoid cyst
+ Neuroepithelial cyst
+ Congenital malformations of the respiratory system
+ Congenital cystic adenomatoid malformation (CCAM)
+ Lobar sequestration
+ Congenital lobar emphysema
+ Pulmonary hyperplasia
+ Pulmonary hypoplasia
+ Congenital pulmonary lymphangiectasia
+ Diaphragm and congenital malformations
+ Congenital malformations of kidneys and efferent urinary tracts
+ Renal agenesis
+ Variations of shape and position of the kidneys
+ Renal cystic disease
+ Infantile polycystic kidneys (ARKPD)
+ Renal dysplasia
+ Adult polycystic kidneys (ADPKD)
+ Autosomal dominant polycystic kidney disease in infant and fetus
+ Lower urinary tract obstruction
+ Posterior urethral valves
+ Congenital tubular renal dysgenesis
+ Urinary bladder
+ Hypospadia
+ Congenital malformations of genital system and somatosexual congenital disorders
+ Somatosexual disorders
+ Somatosexual disorders with normal karyotype
+ Pseudohermaphroditism masculinus
+ Androgen insensitivity syndrome, testicular feminization syndrome, female XY
+ Pseudohermaphroditism femininus
+ Congenital adrenal hyperplasia
+ Somatosexual disorders with pathologic karyotype
+ Congenital malformations of female genitalia
+ Congenital malformations of the internal genitalia
+ Congenital malformations associated with congenital malformations of urinary system
+ Congenital malformations of the vulva
+ Congenital malformations of the male genital organs
+ Cryptorchidism
+ Congenital malformations of penis and scrotum
+ Smith-Lemli-Opitz syndrome (SLOS)
+ Congenital tumors
+ Sacrococcygeal teratoma
+ Congenital cardiac rhabdomyoma
+ Congenital heart defects
+ Defects of heart septum
+ Atrial septal defects
+ Ventricular septal defects
+ AV septal defects
+ Anomalies of the great arteries
+ Transposition of the great arteries
+ Truncus arteriosus
+ Double-outlet right ventricle
+ Malformations of the valves
+ Tricuspid atresia
+ Stenosis and atresia of the mitral valve, the hypoplastic left heart syndrome
+ Stenosis of the pulmonary artery
+ Pulmonary atresia with intact ventricular septum
+ Tetralogy of Fallot
+ Aortic stenosis
+ Malformations of the aortic arch system
+ Persistence of ductus arteriosus
+ Coarctation of the aorta
+ Interruption of the aortic arch
+ Right-sided aortic arch
+ Malformations of the venous system
+ Anomalies of situs and heart position
+ Di George syndrome
+ Congenital malformations of the gastrointestinal tract
+ Oral cavity and the palate
+ Cleft lip and palate
+ Congenital defects of the esophagus
+ Atresia
+ Congenital esophagus stenoses
+ Congenital malformations of the stomach
+ Congenital malformations of the intestines
+ Atresia
+ Malrotation of the intestine
+ Remnants of the omphalomesentric duct
+ Anorectal malformations
+ Duplicatures
+ Defects of the abdominal wall
+ Omphalocele
+ Gastroschisis
+ Limb-body wall complex
+ Pentalogy of Cantrell
+ Developemental anomalies of the skeleton
+ Defects of growth of tubular bone and/or spine
+ Thanatophoric dysplasia
+ Diastrophic dysplasia
+ Abnormalities of density of cortical diaphyseal structure or metaphyseal modeling
+ Osteogenesis imperfecta
+ Limb malformations
+ Terminal transverse limb defects
+ Radial ray defects
+ Finger anomalies
+ Club foot
+ Constriction (amniotic) band syndrome
+ Placental inflammation
+ Ascending infections
+ Placental inflammation, acute
+ Hematogenous infections
+ Fetomaternal listeriosis
+ Pathology of the fetal membranes
+ Amniotic band syndrome
+ Meconium staining
+ Candida infection of the placenta
+ Pathology of the placenta
+ Normal placenta
+ Extrauterine gravidity
+ Gestational trophoblastic disease (GTD)
+ Hydatidiform mole
+ Complete mole
+ Partial mole
+ Invasive mola (mole proliferans, mole destruens)
+ Gestational choriocarcinoma
+ Placental site trophoblastic tumor
+ Placenta and major chromosomal abnormalities
+ Hydropic placenta
+ Pathology of the umbilical cord
+ Abnormal length
+ Short cord
+ Long cord
+ Insertion abnormalities
+ Abnormal coiling
+ Umbilical vessels pathology
+ Umbilical cord accidents which compromise the blood flow
+ Thrombosis of umbilical blood vessels
+ Umbilical cord inflammation
+ Acute funisitis
+ Subacute necrotizing funisitis
+ Miscellaneous rare cord lesions
Smith-Lemli-Opitz syndrome (SLOS)

One of the most frequent AR syndromes in our population (second after the cystic fibrosis). Genetically based metabolic disorder of the cholesterol synthesis which cause wide spectrum of congenital malformations and mental retardation. Congenital malformations of the urogenital tract are characteristic.

Etiology, pathogenesis
  • incidence: 1 : 10 000 – 1 : 40 000
  • carriers (heterozygotes): up to every 30th individual in the population
  • deficit of one of the enzymes for the cholesterol synthesis leads to its deficiency (disorders of cell membranes construction, deficit of steroid hormones, bile acids, myelinisation disorder) and causes structural defects and disorders of the fetus masculinization
Clinical signs

Wide variability of symptomes of this syndrome:

  • phenotypic features of the face (micrognathia, eyelid ptosis, long philtrum and others) and limbs (syndactyly of the 3rd and 4th toe, simian creases and others), microcephaly and others.
  • congenital malformations of the urogenital tract (ambiguous genitalia and other serious malformations of the external genitalia, agenesis, hypoplasia and cystic renal dysplasia)
  • congenital malformations of the central nervous system, cleft palate, congenital heart defects etc.
  • growth retardation
  • Prognosis:
    • fetuses are often spontaneously aborted or stillborn
    • seriously afected newborns die during the first weeks of life, the symptoms are multiorgan failure, evetually heart defects, while less damaged (with phenotypic features, minor congenital malformation such as hypospadia, cryptorchidism, cleft palate) can live to adult age.
    • mental retardation, behavior disorders, failure to thrive
Prenatal diagnosis
  • low estriol level in the screening triple test
  • amniotic fluid examination of cholesterol level and its precursors (metabolites such as 7-DHC are remarkably elevated) in the 2nd trimester
  • chorionic villi sampling (CVS) at the end of the 1st trimester
  • ultrasound: congenital malformation of the fetus

Postnatally the cholesterol level in the serum and its precursors is examined (cholesterol levels are low and the precursors are remarkably increased).

Case study
Smith-Lemli-Opitz syndrome (SLOS)
Marta Ježová

Case of Smith-Lemli-Opitz sydrome in a male 22-week fetus.

Macroscopic appearance
  • external features of the face:
    • microcephaly
    • long philtrum
    • lowered corners of the mouth — fish mouth
  • external genitalia malformation

SLOS, obličej (72458)

SLOS, zevní genitál (72459)


SLOS, 22-week male fetus, general view: SLOS, stigmatisation, Macro, autopsy (72457)

SLOS, external features of the face, side view (micrognathia): SLOS, stigmatisation, micrognathia, Macro, autopsy (72458)

SLOS, external genitalia (hypospadia, ventral penis flexion): Hypospadia, Macro, autopsy (72459)

Skin syndactyly of 2nd and 3rd toe (fork toe): Syndactylia (fork-toe), Macro, autopsy (72460) Syndactylia (fork-toe), Macro, autopsy (72461)

Case study
Smith-Lemli-Opitz syndrom (SLOS)
Marta Ježová

Female infant born at term with abnormal phenotypic features. Corpus callosum agenesis had been diagnosed prenatally. Prenatal karyotype was normal 46 XX. Pulmonary hypertension persisted after birth. The child required ventilation support and failured to thrive. Bilateral congenital cataract was also identified. Attacks of malign arrythmia (ventricular tachycardia, ventricular fibrilation) appeared agonally. The child demised at 1 month of age.

Final diagnosis was made post mortem by DNA analysis: Smith-Lemli-Opitz syndrome.

Direct DNA analysis was carried out in both parents and than the deceased child to search for the most common mutations in the 7- dehydrocholesterol reductase gen (in Czech population).

The childs genotype was p. W151X/ IVS 8-1G>C.

The parents are healty carriers of the mutations.

There is an entire deficiency of the enzym with p. W151X mutation, the affected individuals do not survive 1 month.

Macroscopic appearance
  • external features: postnatal growth retardation, microcephaly, receding forehead, flat occiput, deep-set eyes, broad nasal bridge, low set ears, micrognathia, small tongue, short upper limbs, postaxial polydactyly of the left lower limb, deformed feet (turned outward)
  • brain malformation: microencephaly, partial corpus callosum agenesis, dilated occipital horns of the lateral ventricles
  • heart defect: patent ductus arteriosus, right ventricle hypertrophy
  • abnormal lobation of lungs (there was no lobation at all)
  • icterus, hepatomegaly, intrahepatal cholestasis

SLOS, face (73067)

Hexadactyly (73068)


Icterus, microcephaly, short upper limbs, feet deformity: SLOS, Macro, autopsy (73066)

Microcephaly, flat occiput, receding forehead, low-set ears, mild micrognathia: SLOS, Macro, autopsy (73067)

Hexadactyly: SLOS, Macro, autopsy (73068)

Broad nasal bridge, deep set eyes: SLOS, Macro, autopsy (73069)