A severe and characteristic syndrome of craniofacial
malformations associated with neurological impairment.
Bushy eyebrows, depressed nasal bridge, long philtrum, thin upper lip,
and microcephaly in a boy with Brachmann-de Lange syndrome.
Cornelia De Lange Syndrome; De Lange Syndrome; Typus
First described by the German physician Winfried Robert Clemens Brachmann
in 1916. In 1933, the Dutch pediatrician Cornelia Catharina de Lange reported two more cases and
called the disorder “Typus degenerativus Amstelodamensis”.
1:10,000-40,000 live births.
Autosomal dominant, transmission has been described, however
most cases are sporadic. The defect has been mapped to the Nipped-B-like (NIPBL) gene on 5p13.1.
Based on the clinical findings of characteristic facies in
association with prenatal and postnatal growth retardation and mental
About one-third of these children are born prematurely
and present with prenatal and postnatal growth
retardation resulting in short adult stature (growth hormone deficiency was found in some patients).
Feeding problems often result in failure to thrive. Mild to moderate mental retardation and
hypertonicity are common. Deafness and seizures may occur. Ophtalmological problems may include myopia,
ptosis, microcornea, aniridia, strabismus, and nystagmus. Behavior problems are a common problem in these children
and present as hyperactivity, aggression, and self-inflicted injuries, sometimes
comparable to an “autism-like” behavior. The malformations are complex and involve the head (microcephaly and
brachycephaly) and a short neck with nuchal webbing. The facial features may include low anterior
hairline, bushy eyebrows often with synophrys, low-set ears, depressed nasal bridge, anteverted nares,
micrognathia, long philtrum with thin upper lip, cleft lip, high-arched or cleft palate, downturned corners of
the mouth and widely spaced teeth (often with delayed eruption). The voice is initially often low-pitched,
which resolves as the children grow. Hirsutism and cutis marmorata are frequent. Sketetal involvement may
include scoliosis, limited elbow extension, and dislocation of the radial head, phocoor micromelia, and
anomalies of the usually small hands and feet (oligodactyly, clinodactyly, partial syndactyly). Thoracic features
that have been described are small nipples, short sternum, and supernumerary ribs. Other findings can include
congenital heart defects (in up to 15% of patients; most commonly atrial and ventricular septal defects,
pulmonary stenosis, tetralogy of Fallot), hypopituitarism, and congenital diaphragmatic hernia. Gastrointestinal
problems are common and comprise gastroesophageal reflux (in up to two-thirds of patients; Barrett esophagus and
esophageal scarring have been reported) with recurrent aspirations and pneumonias frequently resulting in
respiratory problems, pyloric stenosis, intestinal malrotation and volvolus. Urogenital anomalies that may
affect renal function are also common and include hydronephrosis, renal dysplasia and cysts, and
vesicoureteral reflux. Furthermore, hypoplastic external genitalia, cryptorchidism and hypospadias have been
described on a regular base. Thrombocytopenia and increased pain tolerance due to decreased pain sensation
have been reported in several patients.
Evaluate neurological function ...