Cutaneous Manifestations of Cornelia de Lange Syndrome Treatment & Management

Updated: Jun 02, 2022
  • Author: Krystyna H Chrzanowska, MD, PhD; Chief Editor: William D James, MD  more...
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Medical Care

A review of management and treatment for Cornelia de Lange syndrome (CDLS) has been published by FitzPatrick and Kline, [95] and management recommendations for older individuals have been reported. [40] Most comprehensive anticipatory guidance includes detailed clinical evaluation at the time of diagnosis, and assessment of different age groups until adulthood. [52]

The results of medical therapy are better in infants than in older children.

Patients with symptoms of gastroesophageal reflux (GER) require intensive medical therapy. Frequent use of antacids, histamine-2 blockers, and metoclopramide can be helpful. [96] Feeding by a nasogastric tube and by having the patient sit upright may be beneficial.

Application of appropriate hearing aids is recommended in children with hearing deficits, although tolerance is poor.

Antiepileptic treatment may be required in a proportion of patients.

Psychoeducational and cognitive-behavioral interventions have been strongly recommended. Clinicians should consider autistic features and refer for further psychological and psychiatric evaluation in order to expedite appropriate intervention. [56]


Surgical Care

During anesthesia, special attention should be given to the risk of malignant hyperthermia (with use of halothane and nitrous oxide), hyperactive airway resulting in bronchospasm, anatomical abnormalities, drug sensitivity, convulsions, and cardiac arrhythmia, because these complications have been reported in children with Cornelia de Lange syndrome (CDLS). [97, 98, 99] Propofol and sevoflurane are recommended most often, because after ketamine, hyperreactivity was noted not infrequently. [99] Endotracheal intubation in this group is associated with an increased risk of complications. [98]

Operative procedures, including Nissen fundoplication and gastrostomy tube (G-tube) placement for feeding, may be necessary in patients with severe esophagitis and in those with worsening failure to thrive despite conservative intervention.

Surgical repair may also be indispensable in patients with diaphragmatic hernia, cardiac defects, or severe skeletal deformities.



Patients may require various specialist consultations, depending on the clinical manifestations and the physical examination findings. Specialists may include the following:

  • Gastroenterologist

  • Cardiologist

  • Pulmonologist

  • Laryngologist/audiologist

  • Ophthalmologist

  • Neurologist

  • Nephrologist/urologist

  • Endocrinologist

Genetic counseling provides families with information on the nature of the disease and the low risk of recurrence. Careful clinical examination of the parents for minor signs is recommended because autosomal dominant inheritance has been implicated in some families (see Prevention).



In general, children with Cornelia de Lange syndrome (CDLS) have difficulty accepting sudden changes in their daily routine and environment.

Activities that stimulate the vestibular system, including swinging, bouncing, swimming, and horseback riding, are pleasurable to the patient.

The use of sign language can help the patient to overcome frustration caused by expressive speech delay.



Genetic counseling and prenatal diagnosis may be offered.

Most cases are sporadic (>99%) and are caused by de novo mutations.

In families with parental transmission of the disease (< 1%), an autosomal dominant or an X-linked dominant mode of inheritance is possible.

In the case of an autosomal dominant mutation in the NIPBL or RAD 21 gene, the risk of transmitting the mutation to offspring is 50%; males and females are affected equally.

In the case of an X-linked dominant mutation in the SMC1A or HDAC8 gene, the risk of transmitting the mutation to offspring is also 50%; however, the affected female will pass the mutation to half of her daughters and sons, and the affected male will pass the mutation to all of his daughters but not to sons.

When parents are not affected, the risk of recurrence has been estimated at 1.5% (germinal mosaicism). [36, 38]

Prenatal diagnosis is possible in families at increased risk of recurrence for Cornelia de Lange syndrome (CDLS), if the mutation (in the NIPBL,SMC1A,SMC3, RAD21, or HDAC8 gene) is precisely identified in the proband before pregnancy. See Lab Studies and the Laboratory Directory at GeneTests.

Ultrasonographic screening for evidence of the manifestations of the syndrome (ie, intrauterine growth retardation, limb defects, diaphragmatic hernia, nuchal translucency) may be helpful. [80, 81, 100, 101, 102] Nuchal translucency has been observed in 46-70% of cases. [103]

A second trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) measurement may have predictive value as an addition to ultrasonography. [104, 103]

Detection of a mild form of Brachmann-de Lange syndrome (BDLS) using 3-dimensional ultrasonography combined with 3-dimensional computed tomography has been reported. [105]


Long-Term Monitoring

Associated developmental abnormalities and disabilities determine further outpatient care.

A systematic auxology evaluation of growth rate using the specific growth chart is recommended. Specifically, this should include standard growth curves for weight, height, and head circumference from birth through adulthood based on serial measurements of patients with clinically confirmed diagnoses of Cornelia de Lange syndrome (CDLS). Ear examination and hearing assessment are recommended for all children every 2-3 years. See the CdLS-USA Foundation website.