CORNELIA DE LANGE SYNDROME

(BRACHMANN-DE LANGE SYNDROME)
  • Amsterdam dwarfism. Although an autosomal dominant inheritance has been suggested, most cases are sporadic,
  • It is a congenital syndrome that features mental retardation, cranial, cardiac, and limb malformations.
  • A single case with a 3q26:17q23 de novo translocation has been reported (1)

 

ULTRASOUND (2)
  • Skull and Facial Bones.
    • Small (microcephaly) and Brachycephaly.
    • Micrognathia.
    • Mouth – long philtrum, thin upper lip with a midline beak, downturned angles of the mouth.
    • High arched palate.
    • Nose – depressed nasal bridge, anteverted nares.
    • Eyes – hypertelorism, bushy eyebrows, long curly eyelashes.

 

Mild hypertelorism.

Thin upper lip with long philtrum (increased distance between the upper lip and nose).

Micrognathia.

Hairy forehead.

 

 

  • Long bones.
    • Micromelia.
    • Hypoplasia of long bones (upper > lower extremity).
    • Short radius and ulnar dysplasia.
    • Dislocation or flexion contractures at the elbows.
    • Forearm bones may be absent.
  • Hands.
    • Thumbs placed proximally (hypoplastic first metacarpal).
    • Short phalanges, clinodactyly of the fifth finger. Occasionally syndactyly of the second and third toes.
    • Hypoplasia of the fourth and fifth metacarpals.
    • Ectrodactyly (claw hand).

 

Ectrodactyly

Proximally placed thumb

Short  hypoplastic 5th metacarpal

46XX karyotype.

Unexplained persistent ascites throughout the pregnancy.

 

  • Cardiac Defects.
    • ASD, VSD, hypoplastic aorta, persistent left SVC, tetralogy of Fallot.
  • Nuchal translucency (increased in the first trimester).
  • IUGR (onset at 20-25 weeks of gestation).
  • Skin – hirsuitism, hypoplastic nipples and umbilicus.
  • Male genitalia – hypoplasia, undescended testis, hypospadias.

 

 

 

Video clip of increased nuchal translucency in Cornelia de Lange Syndrome

 

 

 

DIFFERENTIAL DIAGNOSIS
  1. Apert syndrome.
  2. Fanconi anemia (short radial ray).
  3. Holt-Oram syndrome (heart defect and short radial ray).
  4. Lethal multiple pterygium syndrome.
  5. Roberts syndrome.
  6. Smith-Lemli-Opitz syndrome.
  7. TAR syndrome.

 

 

REFERENCES
  1. Ireland M, English C, Cross I et.al. A de novo translocation t(3;17)(q26.3;q23.1) in a child with Cornelia de Lange syndrome. J Med Genet 1991;28:639-640.
  2. Drolshagen LF, Durmon G, Berumen M et.al. Prenatal ultrasonographic appearance of Cornelia de Lange syndrome. J Clin Ultrasound 1992;20:470-474.
  3. Ireland M, Burn J. Cornelia de Lange syndrome – photo essay. Clin Dysmorphol 1993;2:151-160.