Pathology
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Fetopathology and developmental pathology of the embryo and fetus
Marta Ježová, Josef Feit et al.
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Down syndrome
Etiology

Full trisomy 21 in 95% of the cases.

Clinical signs
  • incidience 1 : 700 livebirths
  • the indicence is directly related to advanced maternal age
  • increased risk of fetal demise
  • mental retardation
  • intrauterine growth retardation, short stature, obesity
  • high relative risk of acute leukemia in the first 5 years of life
  • immunodeficiency, increased risk of bacterial pneumonia in particular
  • there is a shortened life expectancy even if the the survival in individuals with Down syndrome has significantly improved, the estimated life expectancy nowadays is near 60 years
  • congenital heart diseases are major cause of early mortality, 10% of these infants die within the first year of life nowadays
Macroscopic appearance
  • Phenotypic features in a full term infant: brachycephaly, microcephaly, flattened occiput, flat face, upslanting palpebral fissures, epicanthic folds, small nose with broad and flat nasal bridge, open mouth with protruding tongue, slightly abnormal ears, fifth finger clinodactyly, single palmar crease(simian crease).
  • Mongoloid face and brachycephaly cannot be identified in a fetus. Fifth finger clinodactyly and single palmar creases can be easily recognized even in a second trimester fetus. Nuchal edema can be seen in a small fetus, hydrops is rare.
  • Cardiovascular system malformations: in approximately 40% of the cases:
    • AV septal defect, common atrioventricular canal
    • ventricular septal defect
    • atrial septal defect
  • CNS: the brain has abnormal shape, abnormal gyri in the temporal lobe and decreased weight
  • Thymus: hypoplasia, cystic degeneration of Hassall's corpuscles; these findings are probably related to abnormal immune system
  • Gastrointestinal system malformations:duodenal atresia, umbilical hernia.
  • Ultrasonographic findings in trisomy 21:
    • 1st trimestr ultrasonography:
      • Nuchal translucency is subcutaneous accumulation of fluid behind the fetal neck. It looks like a small black space under the fetal neck skin on ultrasonound examination. All major chromosomal defects (trisomy 21, 13,18, Turner syndrome, triploidy) are associated with increased nuchal translucency thickness. The optimal gestational age for measurement of nuchal translucency (NT) is between 11  —  14 weeks. NT greater than 2,5 mm substantially increases the risk of chromosomal abnormality in the fetus. During the second trimestr the translucency usually disappears, sometimes it evolves into either nuchal edema or nuchal cystic hygroma
      • Absent nasal bone: The fetal nasal bone can be visualized by ultrasonography as early as at 11 – 14 weeks. Absent fetal bone (because of delayed ossification of the bone) is detected in approximately 70% of trisomy 21 fetuses. In chromosomally normal fetuses the prevalence of absent nasal bone is less than 1%.
      • Up to 90 % of fetuses with trisomy 21 can be detected in early gestation if the ultrasonographic and biochemical screening are combined.
    • 2nd trimestr ultrasonography
      • Nonstructural markers of chromosomal abnormality:
        • nuchal edema
        • absent nasal bone or nasal bone hypoplasia
        • short limbs (femus, humerus)
        • mild ventriculomegaly
        • mild pyelectasia
      • structural defects:
        • cardiac defects
        • omphalocele
        • duodenal atresia

M. Down, ultrasound (72952)

M. Down, 14. week (73971)

M. Down, 22. week (73972)

M. Down, fetus (72097)

M. Down, AV septal defect (72499)

M. Down, hydronephrosis (72962)

Pictures

Down syndrome, 1st trimester of gravidity: absence of nasal bone, nuchal edema: M. Down, 1st trimester, Ultrasound, video (72952)

Down syndrome, fetus 14-week: M. Down, Macro, autopsy (73971)

15 – week fetus, trisomy 21; marked nuchal edema: m. Down, nuchal edema, Macro, autopsy (72967)

Downův syndrom, fetus 22-week: M. Down, Macro, autopsy (73972) M. Down, Macro, autopsy (73973)

Down syndrome, fetus: Down syndrome, Macro, autopsy (72097) Down syndrome, Macro, autopsy (72098)

Down syndrome, fetus, hand with single palmar crease (simian crease), clinodactyly of the little finger: m. Down, simian crease, Macro, autopsy (72389) m. Down, Macro, autopsy (72390)

Down syndrome, AV septal defect (complete AV canal): AV canal, view from the left ventricle, fetus 18th week of gestation, Macro, autopsy (72501) AV canal, septum with the defect, Macro, autopsy (72500) AV canal, view from the right ventricle, fetus 18th week of gestation, Macro, autopsy (72499)

Stillborn 40-week infant, trisomy 21; intrauterine growth retardation (weight 2600 g), external features  —  flat face, small nose, broad flat nasal bridge; severe maceration: m. Down, intrauterine death, maceration, Macro, autopsy (72963) m. Down, intrauterine death, maceration, Macro, autopsy (72964) m. Down, intrauterine death, maceration, Macro, autopsy (72965)

Male newborn, trisomy 21. Hydroureter (extremely dilated left ureter), bilateral renal dysplasia. The child died of pulmonary hypoplasia: m. Down, hydronephrosis, Macro, autopsy (72962)

M. Down, duodenal atresia: m. Down, duodenal atresia, Macro, autopsy (74369) m. Down, duodenal atresia, Macro, autopsy (74370) m. Down, duodenal atresia, Macro, autopsy (74371) m. Down, duodenal atresia, Macro, autopsy (74372) m. Down, duodenal atresia, Macro, autopsy (74373)

Case study
Morbus Down
Marta Ježová
History
  • 46 – year-old woman, third gravidity
  • Prenatal ultrasound examination (16 weeks):
    • nuchal edema 5 mm
    • mild hydrops
    • absent nasal bone
    • normal anatomy of the heart
  • Fetal karyotype (QF-PCR): trisomy 21

Note: QF-PCR  —  quantitative fluorescence polymerase chain reaction is a method for rapid detection of the most common chromosomal abnormalities.

Macroscopic appearance
  • female fetus, 17. w.g.
  • nuchal edema
  • tiny nose

Nuchal edema (72966)

Pictures

17 – week female fetus, nuchal edema: m. Down, nuchal edema, Macro, autopsy (72966)

Prenatal ultrasound, video: nasal bone is missing: M. Down, 2nd trimester, Ultrasound, video (72953)

Histology

Thymus may be hypoplasic with lymphocyte depletetion, large cystic Hassals corpusles with calcification seem to be characteristic for Down syndrome.

Pictures

Thymus, macerated fetus with Down syndrome: m. Down, calcification of the thymus (abortion), HE 40x (71990)