Cornelia de Lange Syndrome (CdLS)

Description

Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder that affects various aspects of development, including physical features, cognitive abilities, and behavior. It‘s characterized by a unique set of physical characteristics, developmental delays, and other health challenges. This blog will delve into CdLS, exploring its causes, diagnosis, management strategies, and resources for families navigating this condition.

Genes Involved

Cornelia de Lange Syndrome is primarily caused by mutations in genes involved in the regulation of cell division and development. Several genes have been linked to CdLS, including:

NIPBL (NIPBL1): The most common gene associated with CdLS, accounting for about 70% of cases.
SMC1A: A gene involved in chromosome cohesion, accounting for about 10-15% of cases.
SMC3: Another gene involved in chromosome cohesion, responsible for a smaller percentage of cases.
RAD21: A gene involved in chromosome segregation, associated with a rare form of CdLS.
HDAC8: A gene involved in gene regulation, linked to a specific subtype of CdLS with distinct features.

Researchers continue to identify new genes and variants associated with CdLS.

Recognizing the Signs and Symptoms

Cornelia de Lange Syndrome presents a spectrum of features, with severity varying greatly among individuals. Common signs and symptoms include:

Distinctive Facial Features:
- Widely spaced eyes (hypertelorism)
- Thin, arched eyebrows that meet in the middle (synophrys)
- Long, upturned nose
- Small, downturned mouth
- Thin upper lip
- Small chin
Growth and Development:
- Slow growth (failure to thrive)
- Developmental delays in motor skills, speech, and language
- Intellectual disability, ranging from mild to severe
Limb Abnormalities:
- Small hands and feet
- Curved, fifth finger (clinodactyly)
- Fusion of fingers or toes (syndactyly)
- Absent or underdeveloped thumbs
Other Features:
- Heart defects
- Hearing loss
- Vision problems
- Feeding difficulties
- Gastrointestinal issues
- Seizures
- Behavioral challenges, such as anxiety or aggression

It‘s important to note that not everyone with CdLS will experience all of these features. Some individuals may have only a few, while others may have many.

Causes

CdLS is a genetic disorder, meaning it‘s caused by a change in the DNA sequence of one or more genes. In most cases, the mutation is spontaneous and occurs randomly during the formation of the egg or sperm. This means that the parents do not carry the mutation and it‘s not inherited. However, there are also cases where CdLS is inherited from a parent who carries the mutation.

Inheritance/recurrence risk

Inheritance or Recurrence Risk

Sporadic CdLS: The majority of cases are sporadic, meaning they occur randomly without a family history of the condition. The recurrence risk for a subsequent child is very low in these cases.
Inherited CdLS: In rare instances, CdLS can be inherited from a parent who carries the mutation. In these cases, the risk of having another child with CdLS is higher, typically around 50%. Genetic counseling is recommended for families with a history of CdLS.

While the inheritance pattern can vary, it‘s important to remember that CdLS is a complex condition, and the specific inheritance risk for each family can be determined through genetic testing and counseling.

WES Whole Exome Sequencing