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Review
. 2012 Aug;158A(8):1848-56.
doi: 10.1002/ajmg.a.35410. Epub 2012 Jun 27.

Identification of a prenatal profile of Cornelia de Lange syndrome (CdLS): a review of 53 CdLS pregnancies

Dinah M Clark  1 , Ilana Sherer, Matthew A Deardorff, Janice L B Byrne, Kathleen M Loomes, Malgorzata J M Nowaczyk, Laird G Jackson, Ian D Krantz
Affiliations
Review

Identification of a prenatal profile of Cornelia de Lange syndrome (CdLS): a review of 53 CdLS pregnancies

Dinah M Clark et al. Am J Med Genet A. 2012 Aug.

Abstract

Cornelia de Lange Syndrome (CdLS) is a multisystem developmental disorder characterized by growth retardation, cognitive impairment, external and internal structural malformations, and characteristic facial features. Currently, there are no definitive prenatal screening measures that lead to the diagnosis of CdLS. In this study, documented prenatal findings in CdLS syndrome were analyzed towards the development of a prenatal profile predictive of CdLS. We reviewed 53 cases of CdLS (29 previously reported and 24 unreported) in which prenatal observations/findings were available. The review of these cases revealed a pattern of sonographic findings, including obvious associated structural defects, growth restriction, as well as a more subtle, but strikingly characteristic, facial profile, and suggestive of a recognizable prenatal ultrasonographic profile for CdLS. In addition, the maternal serum marker, PAPP-A, may be reduced and fetal nuchal translucency (NT) may be increased in some pregnancies when measured at an appropriate gestational age. In conclusion, CdLS can be prenatally diagnosed or readily ruled out in a family with a known mutation in a CdLS gene. The characteristic ultrasonographic profile may allow for prenatal diagnosis of CdLS in (1) subsequent pregnancies to a couple with a prior child with CdLS in whom a mutation has not been identified or (2) when there are unexplained pregnancy signs of fetal abnormality, such as oligo- or polyhydramnios, a low maternal serum PAPP-A level and/or increased NT, fetal growth retardation, or structural anomalies consistent with CdLS.

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Figures

Figure 1
Figure 1
Plot of fetal growth measurements of four patients with CdLS in whom multiple measurements were available. UA, ultrasound age; GA, gestational age.
Figure 2
Figure 2
Ultrasound findings from select cases with postnatal correlation. a-f) Facial profiles in CdLS pregnancies: a) Facial features at 21 weeks and subsequent 3-D ultrasound (“Case 20” in supplementary digital content); b) Facial features at 28 weeks and postnatal facial features at 28 2/7 weeks (“Case 21” in supplementary digital content); c) Facial profile, ultrasound at 19 weeks, postnatal profile at 1 year (“Case 8” in supplementary digital content); d) Prenatal ultrasound profile at 23 weeks and immediate postnatal profile (“Case 2” in supplementary digital content); e) Prenatal ultrasound of full face at 19 weeks and postnatal full face at 1 year (“Case 8” in supplementary digital content); f) Prenatal ultrasound profile at 18 weeks and postnatal profile at 16 months (“Case 13” in supplementary digital content); g-h) Limb findings in CdLS pregnancies: g) Prenatal ultrasound at 19 weeks showing oligodactyly of upper limbs and 20 week autopsy images (“Case 19” in supplementary digital content); h) Prenatal ultrasound at 23 weeks of right limb showing severe oligodactyly with postnatal conformation (“Case 2” in supplementary digital content).
Figure 3
Figure 3
Flow chart of recommended approach to prenatal diagnosis of CdLS for families with or without a prior CdLS pregnancy.
See this image and copyright information in PMC

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References

    1. Ackerman J, Gilbert-Barness E. Brachmann-de Lange syndrome. Am J Med Genet. 1997;68:367–378. - PubMed
    1. Aitken DA, Ireland M, Berry E, Crossley JA, Macri JN, Burn J, Connor JM. Secondtrimester pregnancy associated plasma protein-A levels are reduced in Cornelia de Lange syndrome pregnancies. Prenat Diagn. 1999;19:706–710. - PubMed
    1. Applewhite L, Rochelson B, McLaughlin J, Vohra N, Bialer M. Prenatal diagnosis of Brachmann-de Lange syndrome using 2-D and 3-D ultrasonography. American Journal of Human Genetics. 2003;73:59.
    1. Arbuzova S, Nikolenko M, Krantz D, Hallahan T, Macri J. Low first-trimester pregnancy-associated plasma protein-A and Cornelia de Lange syndrome. Prenat Diagn. 2003;23:864. - PubMed
    1. Boog G, Sagot F, Winer N, David A, Nomballais MF. Brachmann-de Lange syndrome: a cause of early symmetric fetal growth delay. Eur J Obstet Gynecol Reprod Biol. 1999;85:173–177. - PubMed

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