Cornelia de Lange Syndrome (CdLS) is a rare disease that affects between 1 in 10,000 to 1 in 30,000 newborn babies worldwide.
Symptoms
CdLS 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 (hirsutism)
- Gut symptoms such as episodes of loss of appetite, vomiting, or constipation
Causes
CdLS is caused by mutations in the NIPBL gene in 65% of patients. Less commonly, this condition is due to SMC1A and SMC3 gene mutations, and, rarely, HDAC8 and RAD21 mutations. These four mutations account for 5% of cases. The remaining 30% of CdLS patients do not have any known genetic mutation that is responsible for this disease.
The NIPBL gene regulates a protein called cohesin, whereas SMC1A and SMC3 produce structural parts of this protein. The NIPBL protein has several critical roles in DNA replication and repair.
CdLS is an autosomal dominant condition; therefore, a single abnormal copy of the NIPBL or SMC genes is enough to cause the clinical signs and symptoms of the syndrome. CdLS is almost always due to new mutations; therefore, parents are generally genetically typical. SMC1A and HDAC8 mutations are X-linked, and a single copy is enough to bring on the disease. Both males and females are affected equally CdLS.
Diagnosis and treatment
The diagnosis of CdLS 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.
The management of CdLS involves the following:
- Treatment of heartburn, which is almost universal in CdLS due to gastrointestinal (GI) reflux, which may require surgery to prevent significant damage of the esophagus
- Nutritional support to maintain health
- Physiotherapy, as well as 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
- Monitoring the patient to detect fresh complications or worsening of existing heart, kidney, eye, or hearing complications
