Cornelia de Lange syndrome

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.

 germline mutations in cohesin complex members SMC3 and SMC1A

NB: NIPBL and ESCO2 are also causative of the Roberts syndrome (SC phocomelia syndrome)

See also

  pathology of cohesins

References

 Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, Gil-Rodriguez C, Arnedo M, Loeys B, Kline AD, Wilson M, Lillquist K, Siu V, Ramos FJ, Musio A, Jackson LS, Dorsett D, Krantz ID. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet. 2007 Mar;80(3):485-94. PMID: 17273969

 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