Brachmann-De Lange Syndrome

A severe and characteristic syndrome of craniofacial malformations associated with neurological impairment.

(Figure)

Cornelia De Lange Syndrome; De Lange Syndrome; Typus Degenerativus Amstelodamensis.

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.

Unknown.

Based on the clinical findings of characteristic facies in association with prenatal and postnatal growth retardation and mental retardation.

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 (clinically, electroencephalogram) and ...