Prenatal/neonatal pathology in two cases of Cornelia de Lange syndrome harboring novel mutations of NIPBL.
OBJECTIVE
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).


CONCLUSIONS
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.
Lalatta
Faustina
F
Clinical Genetic Unit, Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Department of Obstetrics and Pediatrics, Milan, Italy. f.lalatta@policlinico.mi.it
Russo
Silvia
S
Gentilin
Barbara
B
Spaccini
Luigina
L
Boschetto
Chiara
C
Cavalleri
Florinda
F
Masciadri
Maura
M
Gervasini
Cristina
C
Bentivegna
Angela
A
Castronovo
Paola
P
Larizza
Lidia
L
D000328:Adult; D018797:Cell Cycle Proteins; D003635:De Lange Syndrome / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D006801:Humans; D010375:Pedigree; D017354:Point Mutation; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D016216:Ultrasonography, Prenatal
D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins