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What is Cornelia de Lange Syndrome?

By Liji Thomas, MD

Cornelia de Lange Syndrome aka CdLS is a rare disease affects 1 in 10,000 to 30,000 newborn babies. It involves many parts of the body, and produces a wide range of signs and symptoms of varying severity. These include:

  • Intrauterine growth restriction, resulting in a small baby
  • Delayed growth and developmental milestones
  • Slow mental development, with minimal or absent speech ability
  • Autistic-like behavior
  • Skeletal abnormalities like limb reduction
  • A characteristic facial shape, which includes unusually arched eyebrows, often joined in the middle to form a single eyebrow
  • Long eyelashes
  • Low-set ears
  • Small wide-spaced teeth
  • Small upturned nose

Other features include:

  • Small head size
  • Short stature
  • Excessive hair growth, called hirsutism
  • Gut symptoms such as episodes of loss of appetite, vomiting or constipation

Cause

It is caused by mutations in the NIPBL gene in 65% of patients. Less commonly it is due to SMC1A and SMC3 gene mutations, and rarely, HDAC8 and RAD21 mutations. These four account for 5% of cases. The NIPBL gene regulates a protein called cohesin, while SMC1A and SMC3 produce structural parts of this protein. This protein has multiple critical roles in DNA replication and repair. 30% of patients do not show any of these mutations.

It is an autosomal dominant condition, so a single abnormal copy of the NIPBL or SMC genes is enough to cause the clinical signs and symptoms of de Lange syndrome. It is almost always due to new mutations, and the parents are generally genetically typical. SMC1A and HDAC8 mutations are X-linked, and a single copy is enough to bring on the disease. It affects males and females equally.

Diagnosis and treatment

Diagnosis is based on the clinical findings, supplemented by molecular genetic testing for mutations in the NIPBL, SMC1A and SMC genes. These tests are not foolproof, however.

Management involves the following:

  • Treatment of heartburn, which is almost universal, due to gastrointestinal reflux, which may require surgery to prevent damage
  • Nutritional support to maintain health
  • Physiotherapy, occupational and rehabilitation therapy to meet the child’s need for ambulation, communication and daily routine activities of living
  • Treatment of associated complications such as heart defects, hearing loss, and seizures
  • Monitor to detect fresh complications or worsening of existing heart, kidney, eye or hearing complications

References

Last Updated: Sep 8, 2015

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