This is a congenital rare genetic condition characterized by the prenatal and postnatal growth retardation, facial abnormalities and intellectual disability. Also known as the cornelia de lange syndrome, the range and severity of symptoms vary among the affected individuals. Although the life expectancy of these children can continue into adulthood, the life-threatening complications such as heart defects should be monitored. This condition is estimated to affect 1 in 10,000 to 30,000 live births.
Causes
This syndrome can result from the genetic mutation in at least five genes; NIPBL, SMC1A, HDAC8, RAD21 and SMC3. Most of the cases are identified with the genetic mutation in the NIPBL gene and the mutation in other genes is less common. All the five genes are responsible for the function of a group of proteins known as cohesion complex that is essential in the developmental role before the birth. This includes the regulation of the organization of chromosomes, repairing damaged DNA, monitoring the activity of certain genes that are responsible for the development of various parts of the body and stabilizing genetic information. The defect in the gene can affect the regulation of this system. In around 30% of the cases, the cause of this syndrome remains unknown.
When a mutation in the genes NIPBL, RAD21 or SMC3 occur, it is believed to be inherited in an autosomal dominant manner meaning one copy of the defective gene can cause this condition. When the genetic mutation in one of the genes; SMC1A or HDAC8 occurs, it is an X-linked dominant pattern where the mutated gene is located in one of the two sex chromosomes meaning males are more likely to be affected.
Symptoms
Children with this condition are often below average weight and commonly present a small size of the head (microcephaly). The developmental delays can range from mild to severe presenting learning disabilities. It is estimated that most of the affected children exhibit gastroesophageal reflux disease. The behavioural issues can consist of self-injury, autistic-like behaviours, obsessive-compulsive disorder, attention deficit disorder and compulsive repetition. The secondary characteristics of this condition can include prominent facial features such as low-set ears, long eyelashes, cleft palate and thin eyebrows that meet at the midline. The limb abnormalities is a common feature of this condition and can consist of small limbs, upper limb abnormalities, missing fingers and/or forearms. Additional abnormalities can include droopy eyelids, inflammation of the eyelid, feeding difficulties, bowel anomaly, undescended testes and a heart defect.
Diagnosis
The diagnosis is based on the clinical evaluation after the birth of the infant or in late childhood. The diagnosis is possible in children who exhibit various features that are characteristic of this condition, however, the diagnosis may be difficult in the mildly affected cases. The genetic testing can confirm the presence of this condition in any one of the five genes identified. The prenatal testing is possible with the ultrasound imaging that can identify the features of this disorder such as retarded growth, limb abnormalities and facial anomalies.
Treatment
The treatment is based on the individual symptoms that are evident in each case. They may require being monitored for complications such as cardiac defect and respiratory infections to ensure prompt treatment. The surgical intervention may be necessary to treat various abnormalities that depend on the severity of the condition and the location such as cardiac defects or to correct the cleft palate. Medications can treat the seizures, gastrointestinal conditions and respiratory infections. Other supportive care may include speech therapy, vocational training and special remedial education.
References
https://rarediseases.org/rare-diseases/cornelia-de-lange-syndrome/
http://www.cdlsusa.org/what-is-cdls/treatment-protocols.htm
https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome#inheritance
