Cornelia De Lange Syndrome

Definition of Cornelia De Lange Syndrome

Cornelia de Lange Syndrome abbreviated as CdLS is a rare type of developmental disorder that is present at birth and affects several body parts. The characteristics of this condition greatly depend on each affected individual and ranges from mild to severe.

Image 1 – Google.com

For about 10,000 to 30,000 newborn babies, there is 1 patient that has the disease which fairly affects males and females. Many individuals with mild or uncommon characteristics of the condition are likely underdiagnosed and might never be identified as having Cornelia de Lange syndrome.

Symptoms of Cornelia de Lange Syndrome

A person with Cornelia de Lange syndrome is commonly distinguished by slow-moving growth before and after birth resulting to short stature. The person may have intellectual impairments that can go from moderate to severe and certain abnormalities of bones in the fingers, arms, and hands.

Almost all individuals with CdLS also possess distinctive facial aspects. Possible symptoms may include:

• Synophrys or arched brows that meet at the center
• Small head
• Low-set ears
• Nose that is upturned and small
• Widely spaced teeth
• Problems with behavior such as autism
• Speech problems
• Limb reduction
• Excessive body hair growth
• Hearing loss
• Seizures
• Eye problems
• Heart deficiencies
• Severe vomiting
• Gastrointestinal problems

Genetics of Cornelia De Lange Syndrome

Cornelia de Lange syndrome could be inherited as an X-linked condition or an autosomal dominant condition although most individuals that are affected with the disease have an abnormal gene resulting to a new gene mutation.

The syndrome could be a result from mutations of these genes:

• HDAC8
• NIPBL
• RAD21
• SMC1A
• SMC3

The most common mutations associated with CdLS are in the NIPBL gene which is recognized in more than 50% of all patients having this condition.

The other genes are not that common. The manufactured proteins coming from all five genes help by contributing to the function or structure of the cohesin complex which is a variety of proteins that plays an essential role in managing development before birth.

The duty of the cohesin complex inside the cells is to help in regulating the structure and arrangement of chromosomes, fix damaged DNA, and stabilizing the cell’s genetic information. Other activity of some genes that guides the development of certain body parts is also regulated by the cohesin complex.

The mutations in the five genes result to Cornelia de Lange syndrome by damaging the task of the cohesin complex which then interrupts the regulation of gene throughout the critical stages of early development. CdLS features widely vary and severity of the condition could even differ in people with the exact gene mutation.

Some researchers suspected that environmental or genetic elements may contribute in determining signs and symptoms in each person. An estimation of 30% in all cases, the cause of the condition is unknown. Researchers continue to look for additional changes in the gene mutations that might cause CdLS.

Treatment of Cornelia De Lange Syndrome

Unfortunately, there is still no cure for Cornelia de Lange Syndrome. Treatments for this condition are targeted towards specific symptoms that each individual experience. The treatment might need the help of a team of specialists to come up with a treatment plan. Affected children and infants are observed closely for certain abnormalities linked with CdLS such as heart problems, glue ear, gastrointestinal defects, and/or respiratory infections in order to ensure an early diagnosis and prompt treatment from a medical specialist. Some patients need surgery depending on how severe the condition is.

The following are health care professionals and with the corresponding symptoms they specialize:

• Speech pathologists – They play a large role in diagnosing and helping a child with the development of language, speech, and feeding skills.
• Pediatricians – They are physicians who manage a child’s behavioral, physical, and mental health beginning from birth until age 21.
• Geneticists – Biologists who specialize in studying the science of genetics.
• Orthopedists – They diagnosis and correct any skeletal abnormalities.
• Surgeons – Physician who specialize in surgical procedures such as closing a cleft palate.
• Gastroenterologists – They help in treating any abnormalities of the digestive tract.
• Urologists – They treat urinary tract disorders.
• Otolaryngologists – They are nose, ears, and throat specialists.
• Cardiologists – They are the ones who diagnose and treat any diseases of the blood vessels and heart.
• Dental specialists – They maintain and preserve oral health.
• Audiologists – They evaluate and treat hearing issues.

Prognosis of Cornelia De Lange Syndrome

A lot of children with Cornelia de Lange Syndrome were able to pull through until adulthood. In some other cases though, children die earlier probably because of gastrointestinal deficiencies and heart anomalies. Intellectual disability is also a typical problem since almost all of them require supervision in their activities, especially to the working circumstances in adults.

Life Expectancy of Cornelia De Lange Syndrome

In the past, numerous of children with Cornelia de Lange Syndrome did not survive past childhood due to their medical needs that were not known. Most individuals now who have the condition live a normal life expectancy. Nevertheless, each child should still be evaluated for life-threatening diseases such as bowel abnormalities, heart deficiencies, and untreated gastroesophageal reflux. Levels of independence depend on each individual with CdLS. Others are able to live on their own and find a job, while some will need lifelong support.

Pictures

Image 2 Source – www.cdlsusa.org

Image 3

References:

1. http://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome
2. https://rarediseases.org/rare-diseases/cornelia-de-lange-syndrome/#symptoms
3. http://howshealth.com/cornelia-de-lange-syndrome/
4. Gil-Rodriguez MC, Deardorff MA, Ansari M, et al (2015 Apr). De Novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia de Lange Syndrome-Overlapping Phenotypes. Hum Mutat. 36 (4):454-62.
5. Huisman SA, Redeker EJ, Maas SM, Mannens MM, Hennekam RC (2013 May). High rate of mosaicism in individuals with Cornelia de Lange syndrome. J Med Genet. 50 (5):339-44.
6. Mende RH, Drake DP, Olomi RM, Hamel BC (2012). Cornelia de Lange Syndrome: A Newborn with Imperforate Anus and a NIPBL Mutation. Case Rep Genet. 2012:247683.