Prenatal/neonatal pathology findings in two cases of Cornelia de Lange syndrome harbouring novel mutations of NIPBL

Purpose: This study reviews prenatal findings in two cases with a suspected diagnosis of Cornelia de Lange Syndrome, a multisystem disorder characterized by somatic defects and mental retardation, that were later confirmed by postmortem examination and molecular testing. Although the correlation between the Cornelia de Lange Syndrome genotype and phenotype is still unclear, preliminary data indicate several severe phenotypic features that are likely to be detected prenatally in NIPBL-mutated patients. Methods: We report on two prenatal/neonatal cases with unusual pathologic findings indicating Cornelia de Lange Syndrome. The first, with suspected Cornelia de Lange Syndrome after a set of typical dysmorphisms was noted by prenatal ultrasound, was confirmed by a physical examination after termination of the pregnancy. The second was diagnosed neonatally on the basis of typical clinical signs. Medical complications led to death within the first month of life. Results: Molecular analysis of NIPBL, the gene that codes for delangin (a component of the cohesin complex), performed postnatally detected two de novo mutations: a missense change (P2056L) in a highly conserved residue and a nonsense alteration (S2490 replaced by a stop codon). Conclusion: We suggest that early diagnosis of Cornelia de Lange Syndrome would be made much easier by the assemblage of a set of prenatal diagnostic features and criteria in Cornelia de Lange Syndrome cases that have been confirmed by direct physical and molecular examinations. We also suggest that Cornelia de Lange Syndrome genotype–phenotype correlations need to be extended to prenatal cases.