Cornelia de Lange syndrome

The Cornelia de Lange syndrome (CdLS) is an extremely rare clinically heterogenous developmental disorder of unknown aetiology.

Epidemiology

The estimated incidence is at ~ 1 : 10,000 - 160,000 births ^ref. There is no recognised racial or gender predilection ⁸.

Clinical spectrum

The syndrome carries a wide spectrum of clinical features which include

• facial dysmorphism
  • low set hairline in the front and back
  • long eye lashes
  • bushy eyebrows
  • up turned nose with anteverted nortrils
  • thin lips with long philtrum
  • microbrachycephaly / microcephaly / brachycephaly
• upper limb malformations 
  • short 1^st metacarpal
  • oligodactyly
  • acheiria
  • micromelia
• growth retardation : including intra uterine growth restriction (IUGR)
• cognitive retardation
• hirsutism
• hearing impairment ²
• intestinal malrotation ³
• congenital diaphragmatic herniation 
• congenital cardiac anomalies
• genito-urinary anomalies
  • hypospadias
  • cryptorchidism

Pathology

Genetics

Most cases are thought to be sporadic resulting in a new autosomal dominant mutation ⁸. 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 CdLS ⁶.

Markers

• abnormally low maternal serum alpha feto protein (MSAFP) * levels have been described in some cases ¹².

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 ^4,13.

Etymology

It was inititially described by Brachmann in 1916 ⁵ but described in its full clinical presentation by Cornelia de Lange in 1933.