= MONGOLISM = TRISOMY 21

Chromosomes: 95% nondisjunction, 5% translocation

Prevalence: 1÷870 live births, most common karyotype / chromosomal abnormality in USA

• mental retardation; hypotonia in infancy
• characteristic facies; Simian crease

• Skull
  • hypotelorism
  • persistent metopic suture (40–79%) after age 10
  • hypoplasia of sinuses + facial bones
  • microcrania (brachycephaly)
  • delayed closure of sutures + fontanels
  • dental abnormalities (underdeveloped tooth No. 2)
  • flat-bridged nose
• Axial skeleton
  • atlantoaxial subluxation (25%)
  • anterior scalloping of vertebral bodies
  • “squared vertebral bodies” = centra high and narrow
    = positive lateral lumbar index (ratio of horizontal to vertical diameters of L2)
• Chest
  • congenital heart disease (40%): endocardial cushion defect, VSD, tetralogy of Fallot
  • hypersegmentation of manubrium = 2–3 ossification centers (90%)
  • gracile ribs; 11 pairs of ribs (25%)
• Pelvis (frontal view)
  • flaring of iliac wings (= rotation of iliac wings toward coronal plane at sacroiliac joints) = “Mickey Mouse ears” / “elephant ears”:
    • decreased iliac angle + index (in 70–80%)
  • flattening of acetabular roof (small acetabular angle)
  • elongated + tapered ischia
• Extremities
  • metaphyseal flaring
  • clinodactyly (50%); widened space between first two digits of hands + feet
  • hypoplastic and triangular middle + distal phalanges of 5^th finger = acromicria (DDx: normal individuals, cretins, achondroplastic dwarfs)
  • pseudoepiphyses of 1^st + 2^nd metacarpals
• Gastrointestinal
  • umbilical hernia
  • “double bubble” sign (8–10%) = duodenal atresia / stenosis / annular pancreas
  • tracheoesophageal fistula
  • anorectal anomalies
  • Hirschsprüng disease

OB-US:

• advanced maternal age
  • In 1÷385 live births for women >35 years of age
  • HOWEVER: 80% of fetuses with Down syndrome are born to mothers <35 years of age
• quad test (2^nd trimester maternal serum screening):
  1. low (0.7 MoM) maternal alpha-fetoprotein (20–30%)
  2. increased (2.04 MoM) hCG (DDx: decreased in trisomy 18)
  3. decreased (0.79 MoM) unconjugated estriol (uE3)
  4. decreased dimeric inhibin A levels
  • Optimal time for test between 15 and 16 weeks GA
  • Detects 75% of cases with Down syndrome with a 5% screen-positive rate
  
  Disadvantage: late performance in 2^nd trimester, 25% of Down syndrome cases not detected, many amniocenteses unnecessarily recommended
• low pregnancy-associated plasma protein A (PAPP-A) at 10–14 weeks EGA

• first-trimester ultrasound markers:
  • nuchal translucency
    = measurement of space between spine and overlying skin on midsagittal view
    Best time: 10w3d – 13w6d EGA
    • ≥5 mm during 14–18 weeks
    • ≥6 mm during 19–24 weeks
      Cause: heart failure, abnormal extracellular matrix, abnormal lymphatic development
  • absent nasal bone
    Best time: between 10 and 14 weeks EGA
  • absent / reversed Doppler flow in ductus venosus during atrial contraction
• major structural malformations:
  Best time: 18 weeks EGA
  • VSD / complete AV canal (50%)
  • cystic hygroma, resolved by 20^th week MA (DDx: Turner syndrome, trisomy 18, trisomy 13, triploidy)
  • omphalocele
  • double bubble of duodenal atresia (8–10%), not apparent before 22 weeks GA
  • hydrothorax
  • mild cerebral ventricular dilatation
  • agenesis of corpus callosum
  • imperforate anus
• minor markers:
  • elevated BPD / femur ratio ← short femur
  • ratio of measured-to-expected femur length ≤0.91 [expected femur length: –9.3105 + 0.9028 x BPD] (sensitivity 40%, specificity 95%, false-positive rate of 2–7%, 0.3% PPV for low-risk population [1÷700], 1% PPV for high-risk population [1÷250])
  • ratio of measured-to-expected humerus length ≤0.90 [expected humerus length: –7.9404 + 0.8492 x BPD] (1–2% PPV for low-risk population; 3% PPV for high-risk population)
  • flared iliac crest = iliac wings rotated toward coronal plane:
    • mean iliac angle at superiormost level of 95.6 ± 11.7° (compared to 76.4 ± 16.8° for euploid fetuses)
  • sandal-gap deformity = separation of great toe (45%)
  • hypoplasia of middle phalanx of 5^th digit resulting in clinodactyly (= inward curve) in 60%
  • mild fetal pyelectasis (17–25%)
  • echogenic bowel at <20 weeks GA (15%, in 0.6% of normals)
  • echogenic intracardiac focus, usually in left ventricle = thickening of papillary muscle (18%, in 5% of normals)
  • frontal lobe shortening (measured from the inner table of the frontal bone to the posterior margin of the thalamus)
  • brachycephaly
  • small cerebellum
  • IUGR (in 30%)
  • polyhydramnios

Cx: leukemia (increased frequency by 3–20 x)