The Cornelia de Lange syndrome is a multisystem developmental disorder characterized by facial dysmorphia, upper-extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities. This disorder is caused in many patients by a mutation in the NIPBL gene with a dominant pattern of inheritance.

Synopsis

 mental retardation
 prenatal growth retardation and postnatal growth retardation
 upper-limb abnormalities
 characteristic facies
 ocular anomalies (#16213388#)

• synophrys (99%)
• long lashes (99%)
• hypertrichosis of the brows (96%)
• ptosis (44%)
• epiphora (22%)
• nasolacrimal duct obstruction (16%)
• blepharitis (25%)
• myopia (58%)
• peripapillary pigment (83%)
• microcornea (21%)

Etiology

 missense and protein-truncating mutations in NIPBL, the human homolog of the Drosophila melanogaster Nipped-B gene (47%). (#15318302#)

• The function of NIPBL in mammals is unknown. The Drosophila Nipped-B protein facilitates long-range enhancer-promoter interactions and plays a role in Notch signaling and other developmental pathways, as well as being involved in mitotic sister-chromatid cohesion.

References

 Strachan T. Cornelia de Lange Syndrome and the link between chromosomal function, DNA repair and developmental gene regulation. Curr Opin Genet Dev. 2005 Jun;15(3):258-64. PMID: #15917200#