What is CdLS?
Unraveling the mystery of Cornelia de Lange syndrome, the most common genetic disorder that causes intellectual disabilities.
A few years back, Cornelia de Lange syndrome was rarely talked about. Now, this rare genetic disorder is becoming well known around the world. What exactly is this syndrome? Let’s learn more about Cornelia de Lange syndrome.
Key Facts
- People with Cornelia de Lange Syndrome are born with it
- The odds of having CdLS are roughly 1 in 10,000 live births
- Experts estimate that 1 out of every 10,000 to 25,000 people is affected by Cornelia de Lange syndrome.
- People with Cornelia de Lange syndrome are more likely than others to exhibit compulsive behavior.
- Many people with Cornelia de Lange syndrome are automatically quiet and may be reticent to talk.
- Approximately 60% of Cornelia de Lange syndrome sufferers engage in some form of self-injurious behavior.
- People who have Cornelia de Lange syndrome may have an overactive response to pain and discomfort in their intestines.
The Syndrome: Clinical Overview
Most people are unfamiliar with Cornelia de Lange syndrome. It is also rare, occurring in approximately 1/10,000 live births. Cornelia de Lange syndrome is a condition where children are born with developmental delays.
Originally called Brachmann-de Lange syndrome after its discoverer, the medical community called it Cornelia de Lange syndrome after the Dutch physician who first described it in 1933.
Cornelia de Lange described two children with the syndrome. They were not related, but their remarkable facial similarities led both the nursing staff and Cornelia de Lange to mistreat them as being the same person. The girls looked so similar that the nursing staff routinely mistakenly thought they were twins.
Because the two children did not have a parent in common, she supposed the medical issue was unique to them. De Lange considered that their condition was genetic.
In 1941, L. de Lange described a third patient with the syndrome, and she presented an account of the syndrome at a meeting of the Neurological Society of Amsterdam. De Lange could not find cases of this sort in thorough research in the library, which indicated that she had described them as a new entity, called ‘typus Amstelodamensis’.
Many doctors and scientists now believe that Cornelia de Lange syndrome is an abnormality of certain genes. The severity of the disorder varies from person to person. However, a lot of research has been made so far that helps us to understand this syndrome even more and also provides interventions with people living with the disorders.
What it is and what it isn’t
There are many misconceptions about Cornelia de Lange syndrome (CdLS) that are due to the lack of awareness of this condition.
People often mistake this condition with cerebral palsy or Down syndrome because of similarities in the physical features, but the differences run deep in the genetic level. Both Cornelia de Lange syndrome and Down syndrome are congenital syndromes that present a phenotypic resemblance, but the genotype is different.
Another misconception is that it is carried by women and can be inherited. In actuality, Cornelia de Lange syndrome is not a sex-linked disorder at all. Males are affected just as often as females. And they are a result of gene mutation during the early stage of conception.
Contrary to a common misbelief, Cornelia de Lange syndrome is not caused by trauma during pregnancy. It is not a syndrome of abuse or neglect. It also does not primarily affect those lower on the social ladder or those with lower incomes or those born to unmarried women. Rather, it is an extremely rare chromosomal disorder that results from a mutation in genes related to child development.
Causes
Multiple genes are involved in the development of Cornelia de Lange syndrome. The genetic causes of Cornelia de Lange syndrome are complex and continue to be researched. It is currently agreed to be caused by a change (mutation) in one of the five genes:
- NIPBL
- SMC1A
- SMC3
- RAD21
- HDAC8
Proteins from the genes listed above have important roles before births. All of these genes play a key role in the development of a baby’s brain, face, and limbs. They regulate the structure and organization of chromosomes. Proteins are very important molecules created by genes in your DNA.
Chromosomes carry genes that are essential for early brain and face development before the birth of the baby. A disruption of the gene-regulating protein production during stages of early development can lead to congenital deformities at birth found in people living with CdLS Syndrome.
Risk factors
The main reason for severe physical anomalies observed in Cornelia de Lange syndrome is chromosomal issues. Although Cornelia de Lange syndrome has not yet been linked to inheritance, current research suggests that chromosomal abnormalities are the main cause of physical anomaly in patients with this disorder.
Further research into this subject is needed to determine the risk factors. As at present, it is clear that proper care and treatments can improve outcomes for patients with Cornelia de Lange syndrome.
A Closer look at Sign and Symptoms
Individuals with mild Cornelia de Lange syndrome will often have many facial characteristics but with less severe cognitive and limb differences. This syndrome primarily affects physical and intellectual characteristics and shows symptoms for both.
Physical Symptoms
Physical symptoms of Cornelia de Lange syndrome can be identified in facial features, body measurements, and the size of limbs. Consider the following symptoms to properly diagnose this disorder:
Facial features
The facial features of Cornelia de Lange syndrome are distinct from this kind of syndrome. There is a somewhat puffy, fullness around the eyes. Due to the fullness in the lower third of the face, there comes an impression that the person has an open mouth, or is about to smile. The lips are thin and lined with creases.
Other facial features include epicanthal folds, smallmouth, short upturned nose, thin upper lip, long philtrum with the thin upper lip.
Limb Differences
CdLS causes partial to full limb differences. It is characterized by abnormalities of the foot, toes, thumbs, hands, and wrists. This includes webbing of the toes, duplicated or missing fingers or thumbs, small feet or hands with absent or abnormally small thumbs and fingers.
Hirsutism
Hirsutism is the term used to describe an excessive amount of hair. It is one of many complications that may arise from an X-linked disorder of Cornelia de Lange Syndrome.
Some of the most common areas where hair grows are on the upper lip, chin, chest, abdomen, around the eyes, and abdomen. Other symptoms of hirsutism include male pattern baldness and thin eyebrows.
Sensory Impairments
While numerous physical sensory impairments may be associated with Cornelia de Lange syndrome, vision and hearing loss are the two most common and occur in 50 and 90 percent of patients respectively.
The visual abnormalities that affect individuals with this genetic disorder include strabismus, reduced reaction time, or nystagmus.
Individuals with Cornelia de Lange syndrome may also experience decreased sensation and/or perception of hot and cold temperatures. This symptom typically occurs in both hands and feet, and the sensory-related symptoms can be severe enough to cause severe pain, even with minor injuries or swelling of the affected area.
Due to this pain, the affected person may withdraw from social interaction and physical contact—a sign of tactile defensiveness.
Birth Weight and Size
Children with Cornelia de Lange syndrome have significantly lower birth weights than other children. This low birth weight is present in most children with the disorder and remains throughout life. Their average height is also shorter than the average adult height and has distinctive facial features.
Intellectual Characteristics
Intellectual disability is a spectrum of cognitive, mental, and learning impairments that can range from mild to severe.
People with Cornelia de Lange Syndrome usually have average to low intellect. Studies suggest that the IQs of people with this condition range from 30 to 86, with a mean of 53.
Individuals who have Cornelia de Lange Syndrome have less cognitive impairment due to genetic mutation. Individuals with SMC1A or SMC3 mutation have fewer physical features of the syndrome, but still, have moderate to severe intellectual disability.
Behavioral Symptoms
A range of behaviors and characteristics can be seen in people with Cornelia de Lange syndrome. Biological and psychosocial issues can occur however these will vary from person to person.
Behaviors of Cornelia de Lange syndrome are a great way to understand a person with CdLS. They can provide insight into why behavior happens and symptoms can be addressed with appropriately customized ways of helping a person with this syndrome
People with Cornelia de Lange Syndrome often display behavioral symptoms including:
- Lack of awareness
- Low tolerance for frustration
- Mood swings
- Persistent crying
- Autism spectrum disorder
- Sleeping difficulty
- Social Anxiety
- Impaired communication Skills
- Self-injurious behaviors e.t.c
A crucial step in managing behavioral challenging behaviors is to establish an adequate support system, including both family members and professionals. Similarly, Effective communication is critical for independence. If individuals with intellectual disabilities do not learn alternative methods of communication, they may seem to be non-compliant.
Diagnosis
Healthcare professionals use clinical diagnosis and genetic testing to diagnose CdLS.
Prenatal Diagnosis
Although it is difficult to receive a prenatal diagnosis of Cornelia de Lange syndrome outside of a familial pathogenic variant, CdLS may sometimes be suspected before birth through the use of ultrasound imaging.
During the ultrasound, reflected sound waves create an image of the fetus that may reveal certain abnormalities, such as limb abnormalities or facial anomalies, which are characteristic of CdLS.
Clinical Diagnosis
Diagnosis of Cornelia de Lange Syndrome is done in the neonatal period when there is a discrepancy between the physical appearance and the developmental level of a child. CdLS is diagnosed clinically based on specific signs and symptoms, including physical observations, taking a patient’s medical history, and running laboratory tests.
Genetic Testing
One of the misconceptions about CdLS is that there are no genetic tests to determine which gene has caused the syndrome. As with most diseases, genetic testing for CdLS depends upon knowing what genes or genes are affected.
Many laboratories offer genetic testing for CdLS. There are numerous ways to test for the CdLS mutation. Genomic DNA sequencing (sometimes referred to as whole-exome sequencing) is commonly used to sequence all of the protein-coding sections of each gene in an individual’s genome.
This is usually called panel sequencing, and it is presently the most effective way of detecting causative variants in any of the genes known to cause CdLS. The specific list of genes varies among laboratories but should include all genes known to be causative for CdLS or found in
Therapies and Interventions
The treatment of Cornelia de Lange syndrome involves a combination of therapies aimed to relieve the symptoms unique to each individual. None of the treatments is curative; rather, they are palliative or preventative.
Caring for a child with CdLS requires the efforts of a team of specialists working together to develop and carry out an individual treatment plan. The treatment may involve pediatricians, geneticists, surgeons, orthopedists, plastic surgeons, and orthopedic surgeons.
In children with mild to moderate disfigurement, surgical procedures may help reduce excess body hair and address minor facial defects. Procedures may include additional surgeries to the ears, nose, or mouth as well as plastic surgery to reshape overly prominent ears or correct indentations in the sides of the nose known as columella protuberances.
In most cases, respiratory infections are treated with antibiotics and/or other medications.
Early Interventions
Early intervention services, including specially designed instruction that begins shortly after birth to promote development and learning, can help children with CdLS achieve developmental milestones and learn skills they need for later life.
However, the appropriate amount of therapy needed to meet individual needs will likely differ from child to child. Specialized education can make a huge difference in children with Cornelia de Lange. Vocational training gives them the skills to work outside of their disabilities, while speech therapy allows individuals to communicate more effectively.
When a child is exhibiting signs of Cornelia de Lange syndrome, it’s recommended that parents seek genetic counseling.
Cornelia de Lange syndrome today – What’s new?
A disorder that has been misunderstood for years, CdLS is beginning to see significant improvements in research and treatment. CdLS does not cause the same impact nowadays.
The more we understand about this condition, the more we can help people with it lead a fulfilling life. We provide new opportunities that allow people with CdLS to express their creativity and fulfill new ambitions.
Also, there are many foundations that help this syndrome, doctors that help patients in the medical field and parents in need. Many foundations are in progress to find treatments for this disease.
