GENERAL FEATURES OF DOWN SYNDROME

• Most common chromosomal abnormality (once in every 660 live-births).
• 95% - extra chromosome 21.
  3% - due to translocations.
  2% - mosaics.
• The major abnormalities associated with trisomy 21 are expressed by the genes located at the q22 band of chromosome 21.
• Recurrence risk for trisomy 21 is 1% for women under 30 years of age. Recurrence risk for older patients is the same as the risk associated with their age.
• Table of age specific risk for trisomy 21 in the first and second trimesters and at delivery.
• Maternal serum screening. In trisomy 21, a-fetoprotein levels decrease, urinary E3 levels decrease and bhCG levels increase.

Sensitivity and False Positive Rates for Sonographic Markers in Detection of Second-Trimester Fetuses with Trisomy 21 (1)
Sonographic Finding	Trisomy 21	False positive rate	Score
Any major fetal anomaly	24.5%	2.8%	2
Nuchal Fold 6 mm or greater	50.9%	0.6%	2
Short humerus (ratio <0.90)	41.3%	3.4%	1
Short femur (ratio <0.91)	47.2%	7.9%	1
Hyperechogenic bowel	24.5%	2.3%	1
Echogenic Intracardiac focus	30.2%	4.5%	1
Pyelectasis (AP diameter 4mm or greater)	22.6%	0.6%	1
Score of greater than or equal to 1 (risk)	83%	17.5%
Score of greater than or equal to 2 (risk)	75.5%	5.7%

Minor and major markers of chromosomal aneuploidy
	Nuchal edema or fold of above 6mm · May result from increased nuchal translucency in the first trimester. · Found in 0.5% of fetuses. · May be of no pathological significance. · May be associated with: o Chromosomal defects. o Cardiac anomalies. o Fetal infection. o Genetic syndromes. · Risk of trisomy 21 in cases of isolated nuchal edema may be 15 times the background risk.
	Short femur or humerus If this measurement is below the 5^th percentile and all other measurements are normal this is likely to be normal. Occasionally a sign of chromosomal defects. Short femur is found four times more commonly in trisomy 21 than in normal fetuses.
	Echogenic intracardiac foci Found in up to 4% of pregnancies. May occasionally be associated with chromosomal abnormalities. Risk of trisomy 21 with isolated echogenic cardiac foci may be four times the background risk.
	Hyperechogenic bowel Found in about 0.5% of fetuses. Causes include: Normal variant. Intra-amniotic bleeding. Fetal infection. Cystic fibrosis. Risk for trisomy 21 may be up to three times the background.
	Mild pyelectasis (4mm or greater) Found in up to 2% of pregnancies and is usually not pathological. Risk for trisomy 21 is about 1.5 times the background risk. Follow up recommended at 26-28 weeks to exclude renal obstruction.
	Choroid plexus cysts Found in up to 2% of pregnancies and usually of no pathological significance if isolated. High risk of chromosomal aneuploidy, especially trisomy 18, when other defects are present. Risk of trisomy 18 and possible trisomy 21 is about 1.5 times the background risk when isolated.
	Ventricular Disproportion LV / RV disproportion. Echogenic intracardiac foci LV.

Likelihood ratios (sensitivity/false-positive rate) of sonographic findings associated with Down syndrome Nyberg et.al. J Ultrasound Med 2001;20:1053-1063
Sonographic marker	Overall likelihood ratio (*)	Likelihood ratio as an isolated marker (**)	95% CI
Nuchal thickening	61	11	5.5 - 22
Hyperechoic bowel	33.8	6.7	2.7 – 16.8
Short humerus	15.3	5.1	1.6 – 16.5
Short femur	6.1	1.5	0.8 – 2.8
EIF	6.3	1.8	1.0 – 3.2
Pyelectasis	5.2	1.5	0.6 – 3.6
(*) – likelihood ratio when a marker was present either as an isolated finding or in combination with other markers. (**) – likelihood ratio when a marker was present as an isolated finding. EIF – echogenic Intracardiac focus.

REFERENCES

Bromley B, Lieberman E, Benacerraf BR. The detection of Down syndrome using a scoring index of sonographic markers and maternal age. Ultrasound Obstet Gynecol 1997;10:321-324.