de Lange Syndrome Treatment & Management

  • Author: Krystyna H Chrzanowska, MD, PhD; Chief Editor: William D James, MD  more...
 
Updated: Aug 30, 2016
 

Medical Care

A review of management and treatment for Cornelia de Lange syndrome (CDLS) has been published by FitzPatrick and Kline,[91] and management recommendations for older individuals have been reported.[44] Most comprehensive anticipatory guidance includes detailed clinical evaluation at the time of diagnosis, and assessment of different age groups until adulthood.[48]

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.[92] 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.[51]

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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).[93, 94, 95] Propofol and sevoflurane are recommended most often, because after ketamine, hyperreactivity was noted not infrequently.[95] Endotracheal intubation in this group is associated with an increased risk of complications.[94]

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.

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Consultations

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 Deterrence/Prevention).

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Activity

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.

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Prevention

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.[73, 74, 96, 97, 98] Nuchal translucency has been observed in 46-70% of cases.[99]

A second trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) measurement may have predictive value as an addition to ultrasonography.[100, 99]

Detection of a mild form of Brachmann-de Lange syndrome (BDLS) using 3-dimensional ultrasonography combined with 3-dimensional computed tomography has been reported.[101]

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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 Web site.

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Contributor Information and Disclosures
Author

Krystyna H Chrzanowska, MD, PhD Professor and Head of Genetic Counseling Unit, Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland

Krystyna H Chrzanowska, MD, PhD is a member of the following medical societies: European Association for Cancer Research, European Society of Human Genetics, Polish Academy of Sciences, Polish Genetics Society, Polish Pediatric Society, Polish Society of Human Genetics

Disclosure: Nothing to disclose.

Coauthor(s)

Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, Rutgers New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Jolanta Wierzba, MD Associate Professor, Department of Infant Pathology in the Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Poland

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Albert C Yan, MD Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine

Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology, Society for Pediatric Dermatology, American Academy of Pediatrics

Disclosure: Nothing to disclose.

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  101. Le Vaillant C, Quere MP, David A, et al. Prenatal diagnosis of a 'minor' form of Brachmann-de Lange syndrome by three-dimensional sonography and three-dimensional computed tomography. Fetal Diagn Ther. 2004 Mar-Apr. 19(2):155-9. [Medline].

 
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Case study 1. Classic de Lange phenotype is shown. Facial characteristics of a 10-month-old girl are pictured. Note well-defined eyebrows with synophrys, depressed nasal bridge, and long smooth philtrum.
Case study 1. Lateral facial profile is pictured. The eyebrows are neat, arched, and well defined. The nasal bridge is depressed, and the nares are upturned.
Case study 1. The patient, aged 5 years, is shown; note microbrachycephaly, well-defined eyebrows, anteverted nares, long and thin upper lip, down-turned angles of mouth, and widely spaced teeth.
Case study 1. Upper limb reduction anomalies are pictured with only 2 fingers present.
Case study 1. Note short hypoplastic fifth finger.
Case study 1. Small feet with short hypoplastic toes and syndactyly of the second and third toes is pictured.
Case study 2. Mild de Lange syndrome is shown. The face of a 1.5-year-old girl is pictured. Note neat eyebrows with delicate synophrys, long eyelashes, depressed nasal bridge, upturned nares, long philtrum, thin upper lip, and small chin.
Case study 2. Lateral facial profile shows depressed nasal bridge, thin upper lip, and small mandible.
Case study 2. The patient, aged 8 years, is shown; note delicate synophrys of the eyebrows, upturned nares, long philtrum, and thin upper lip.
Case study 2. Lateral facial profile of the patient, aged 8 years, is shown.
Case study 3. de Lange syndrome patient. Six-year-old patient with HDAC8 mutation. Some distinct clinical features such as hypertelorism and hooding of the eyelids are more characteristic for this type of mutation.
 
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