535Serum tests used to screen for Down’s syndrome include β-human chorionic
gonadotrophin (hCG), alpha-fetoprotein (AFP), unconjugated estriol (uE3), serum
pregnancy associated plasma protein-A (PAPP-A), and dimeric inhibin A. ADAM12,
a novel serum marker with biological properties similar to PAPP-A.
The Serum, Urine and Ultrasound Screening Study (SURUSS) advanced our
knowledge of the effi cacy and safety of antenatal screening for fetal Down’s syn-
drome and placed choices on a fi rmer platform of evidence. The best performer was
the integrated test, comprising ultrasound measurement of fetal nuchal translucency
and assay of PAPP-A at 10 weeks, combined with quadruple tests of serum
α-fetoprotein, unconjugated estriol, hCG, and inhibin-A during the second trimester
(after 14 weeks). This two step package had a false positive rate of only 0.9 %. The
best fi rst trimester screening package was a combination of nuchal translucency
scan, serum free β-HCG, and pregnancy associated plasma protein A, which had a
false positive rate of 4.3 %. Second trimester quadruple testing alone had a false
positive rate of 6.2 %.
Quadruple Marker Prenatal Screening Test (Laboratory Corporation of America)
is a blood screening test done in the second trimester of pregnancy (between 15 and
20 weeks) to help detect an increased risk for Down’s syndrome, trisomy 18, and
neural tube defects or abdominal wall defects. Occasionally, the test may also detect
a risk for other chromosome abnormalities. This test measures the concentrations of
four biochemical substances produced by the fetus and placenta, AFP, hCG, uE3,
and dimeric inhibin A. The test values, together with maternal age, are then entered
into a mathematical formula to determine the risk for the various abnormalities. By
adding a fourth marker to the prenatal screening test, the detection rate for an ele-
vated risk of Down’s syndrome can be increased from 60 % to 75 %.
Biomarkers for Muscular Dystrophy
Duchenne and Becker muscular dystrophy (DMD and BMD) share clinical symp-
toms like muscle weakness and wasting but differ in clinical presentation and sever-
ity. Immunohistochemistry using antibodies to dystrophin is the pathological basis
for the diagnosis of DMD and BMD. While the sarcolemma of DMD muscle is
negative, BMD muscle generally shows variable labeling because of the translation
of a partially functional dystrophin that is localized to the sarcolemma. In some
cases this differentiation is not possible. In such instances immunolabeling with
antibodies to the neuronal form of nitric oxide synthase (nNOS) can be useful in
suspecting a dystrophinopathy with a mutation in the ‘hot-spot’ rod domain and
help to direct molecular analysis. nNOS localizes to the sarcolemma of mature mus-
cle fi bers via several components of the dystrophin-associated protein complex
including dystrophin but sarcolemmal nNOS is lost when dystrophin levels are very
low or absent because of deletions in critical regions of the rod domain.
Biomarkers for Genetic Disorders