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Cornelia de Lange syndrome (CdLS) is an autosomal congenital disease caused by mutation of the NIPBL gene in 50% of cases, with a frequency of 1 in 10 000 to 1 in 100 000 live births[1-3]. It is mainly characterized by dysmorphic features, growth restriction, hypertrichosis, upper limb defects and visceral malformations[4]. The associated mental retardation makes this syndrome a severe one. Although several cases and series of prenatal diagnosis of CdLS have been reported, prenatal diagnosis remains challenging, with only 23% of all cases being detected prenatally[5, 6]. We report on the prenatal diagnosis of a fetus with CdLS which was prompted by ultrasound visualization of long eyelashes.

A 41-year-old Caucasian woman, gravida 8 para 4, was referred at 26 weeks' gestation to our prenatal diagnosis center to explore a left congenital diaphragmatic hernia (CDH) revealed in her second routine ultrasound examination. Her obstetric history consisted of four normal pregnancies with term delivery and three early miscarriages. Her medical and family histories were unremarkable. The woman and her partner were not consanguineous. The first screening ultrasound scan, at 13 weeks' gestation, showed a crown–rump length of 71 mm and a nuchal translucency thickness of 1.3 mm. Karyotyping performed following amniocentesis was normal. Ultrasound examination performed at 26 weeks' gestation by an experienced sonographer (E.V.), using a 5–7-MHz curved array transducer with a Toshiba Aplio monitor (Tochigi-ken, Japan), confirmed the left CDH and revealed moderate intrauterine growth restriction (IUGR), around the 5th percentile. A coronal view of the face revealed the presence of long eyelashes (Figure 1a). From these findings, CdLS was strongly suspected, and a very low level of pregnancy-associated plasma protein-A (PAPP-A) (0.005 multiples of the median) sampled at 29 weeks' gestation strengthened the diagnosis. The prognosis was explained to the couple by geneticists, and they decided to terminate the pregnancy. The woman delivered a 1466 g (10th percentile) female baby at 32 weeks' gestation.

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Figure 1. (a) Coronal ultrasound image of the face of a fetus with Cornelia de Lange syndrome, showing long eyelashes (arrows). (b) Photograph of fetal face after termination of pregnancy confirms presence of long eyelashes.

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An autopsy was performed at the request of the parents and this confirmed the diagnosis of CdLS. The fetus was slightly growth restricted and presented dysmorphic features, and CDH was confirmed. External examination confirmed the presence of long eyelashes (Figure 1b). Genetic analysis revealed a de novo mutation of the NIPBL gene.

Prenatal diagnosis of congenital syndromes is a challenge in fetal medicine and is often based on a combination of several signs, CdLS being a perfect example. The main feature that generally leads to a prenatal diagnosis of CdLS is defective upper limbs. Although they are observed in 73.1% of cases, there is a wide spectrum of severity and they can be represented by minor anomalies not visible on ultrasound[6]. Other associated features such as IUGR, CDH, heart defects and low PAPP-A level can help to strengthen a diagnosis[7]. CdLS is characterized by generalized hypertrichosis resulting in synophrys and long eyelashes. Given the difficulty of prenatal diagnosis of CdLS, ultrasound detection of long eyelashes which, as we have shown, is easily achievable using a coronal view of the face from 26 weeks' gestation, could help in the prenatal diagnosis of this severe congenital syndrome. The diagnostic value of this sign will be enhanced by association with the other classical features of the syndrome.

  • E. Spaggiari*†‡, E. Vuillard§, S. Khung-Savatovsky,

  • F. Muller¶**, J.-F. Oury§‡, A.-L. Delezoide†‡ and

  • F. Guimiot†‡

  • Department of Developmental Biology, AP-HP,

  • Robert Debré Hospital, Paris, France;

  • University Paris Diderot and Paris Sorbonne-Cité,

  • Paris, France; §Department of Obstetrics

  • and Gynecology, AP-HP, Robert Debré Hospital,

  • Paris, France; Department of Biochemistry and Hormonology, AP-HP, Robert Debré Hospital,

  • Paris, France; **University Paris Ile de France Ouest,

  • Versailles Saint-Quentin, France

  • *Correspondence.

  • (e-mail: spaggiari2002@yahoo.fr)

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