Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is an extremely rare clinically heterogeneous developmental disorder of unknown etiology. Although the described clinical symptomatology is very broad, the majority of cases include growth impairment, learning disability and dysmorphic facies.

Epidemiology

The estimated incidence is at ~1:10,000-30,000 births . There is no recognized racial or gender predilection .

Clinical presentation

The syndrome carries a wide spectrum of clinical features which include:

Pathology

Genetics

Most cases are thought to be sporadic resulting in a new autosomal dominant mutation . Occasional autosomal dominant and autosomal recessive forms are known. Some have abnormalities in chromosome 3q26.3. Heterozygous mutations in the cohesin regulator, NIPBL, or the cohesin structural components SMC1A and SMC3, have been identified in approximately 65% of individuals with Cornelia de Lange syndrome . Other implicated genes are RAD21 and HDAC8 .

Markers
  • low PAPP-a
  • abnormally low maternal serum alpha fetoprotein (MSAFP) levels have been described in some cases

Radiographic features

Antenatal ultrasound

May demonstrate many of the above clinical features. An early - first trimester - ultrasound scan may show an increased nuchal translucency as a non-specific but early sign .

History and etymology

It was initially described by Brachmann in 1916 , but described in its full clinical presentation by Cornelia de Lange in 1933.