Pregnancy‐associated plasma protein A: A possible marker in the classification and prenatal diagnosis of Cornelia de Lange syndrome

Abstract

The concentration of human platelet lactogen (hPL), pregnancy specific beta-1 glycoprotein (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were analysed in consecutive serum samples from a patient who gave birth to a child with Cornelia de Lange syndrome. HPL and SP-1 were present in normal concentrations from week 20 to week 35 of gestation whereas PAPP-A could not be detected in any of the samples examined. Immunohistochemical examination of two placentae from Cornelia de Lange syndrome revealed normal localization of hPL and SP-1 but the absence of PAPP-A from the syncytiotrophoblast. The significance of association between Cornelia de Lange syndrome and compromised synthesis of PAPP-A is discussed.

Low Unconguted Estriol Levels in the Maternal Quadruple-Marker Screen in a Fetus with Cornelia de Lange Syndrome and a Partial Deletion of the <i>NIPBL</i> Gene

“…The use of maternal serum AFP, hCG, and uE 3 predicts 70% of fetuses diagnosed with trisomy 18. Low levels of uE 3 , less than or equal to 0.5 MoM, have been associated with adverse pregnancy outcomes: IUGR and early fetal loss. Levels less than 0.25 MoM are indicators that the fetus might be experiencing congenital adrenal hypoplasia, steroid sulfates deficiency, or Smith-Lemli-Opitz syndrome [8,9].…”

“…Similarly, low first and second trimester maternal serum pregnancy-associated plasma protein A (PAPP-A) have been associated with CdLs. The difficulty here is that PAPP-A measurements must be taken over a period of time, and PAPP-A is not a fetal analyte that is routinely measured in maternal serum during second trimester pregnancy screening tests [3,4,5].…”

“…The combined evaluation of maternal serum AFP, hCG, uE 3 , and maternal age have value in predicting risk for fetal chromosomal abnormalities during pregnancy. The use of maternal serum AFP, hCG, and uE 3 predicts 70% of fetuses diagnosed with trisomy 18.…”

Cornelia de Lange syndrome (CdLS): prenatal and autopsy findings

“…Nonsense, missense, frameshift and splicing mutations have all been identified, and severity is associated with presence of mutation and truncating lesions (Krantz et al, 2004;Tonkin et al, 2004 Prenatally, both large nuchal translucency and cystic hygroma have been reported in the first trimester ultrasound (Urban et al, 2001;Huang et al, 2002). Furthermore, cases with a low second trimester PAPP-A (below 0.20 MoM) were reported (Westergaard et al, 1983;Aitken et al, 1999) and Arbuzova et al (2003) reported a case with low PAPP-A detected at 11 weeks in a pregnancy that was terminated for multiple anomalies including growth retardation, limb reduction abnormalities, clubfoot and oligohydramnios, and on postmortem examination and mutation analysis of the NIPBL gene confirmed the diagnosis of CdLS. We report three cases of CdLS detected prenatally.…”

Mutational Screening and Prenatal Diagnosis in Cornelia de Lange syndrome

“…-The typical in utero facial profile of a fetus with CdLS, consisting of micrognathia, a prominent upper-lip, and a depressed nasal-bridge with somewhat anteverted nares [10][11][12]. -Maternal serum PAPP-A level may be low in the first and second trimester, if the fetus has CdLS [13][14][15].…”