THE GENETICS OF CdLS
Genetic testing is often used to identify or confirm a CdLS diagnosis. To date there are seven gene variants that can cause CdLS.
Know your genes!
In the future, researchers may identify additional gene changes that cause CdLS. Research helps us better understand why and how CdLS occurs.
A genetic counselor can help explain this information and discuss how this may impact your family planning decisions.
If you need help finding a genetic counselor, ask your CdLS World Community in your country through our Ask The Expert service
CdLS, does it matter if you are a Male or Female?
- Five of the seven genes identified (NIPBL, SMC3, RAD21, ANKRD11, BRD4) are located on one of the other 22 pairs of chromosomes (outside the magnifier glass) that have exactly the same effect with Males and Females.
- Two of the seven genes (SMC1A and HDAC8) identified are located on the X chromosome. (inside magnifier). For these it is important to know if it is a dominant mutation if you are concerned with inheritance
WHAT IS CORNELIA de LANGE SYNDROME (CdLS)?
CdLS is a rare genetic spectrum disorder present from birth. This means that during conception a gene changed or mutated. Most of the time, the gene change occurs spontaneously and has not been passed down from either parent. On occasion, the gene change can be inherited when parents who do not have CdLS have the variant in some of their egg or sperm cells.
CdLS can cause a broad range of potential physical, cognitive, and medical challenges. Physical features and medical conditions occur along a continuum with varying degrees of severity. No two individuals with CdLS are the same. It is estimated that CdLS occurs in 1 in 10,000 live births, affecting all races and genders equally. CdLS can remain undiagnosed because it presents in different forms and severity.
MANAGEMENT GUIDELINES
Identifying concerns and initiating treatment to address medical and developmental issues are vital. The CdLS Management Guidelines outline necessary evaluations, and tests, recommended at different ages and intervals.
MOST COMMONLY AFFECTED BY CdLS
| Gene Variant/ Change | Cardiac / Cardiovascular | Cognition and Behavior | Digestive System | Genitourinary | Head and Facial Features | Neurological | Skeletal System | Vision problems /Hearing Loss |
|---|---|---|---|---|---|---|---|---|
| NIPBL | ||||||||
| SMC1A | ||||||||
| HDAC8 | ||||||||
| SMC3 | ||||||||
| RAD21 | ||||||||
| ANKRD11 | ||||||||
| BRD4 |
FINDINGS YOU MAY SEE
Cardiac / Cardiovascular
- Congenital heart defects
Cognition and Behavior
- Intellectual or learning disability (any degree)
- Autism spectrum disorder
- ADHD, Anxiety
- Self-injurious behavior
- Behavioral issues can escalate in response to discomfort from a medical issue
Digestive System
- Gastrointestinal reflux (GERD): at least 85% of those with CdLS experience some type of reflux
- Constipation, decreased bowel motility
- Chance of bowel obstruction
Genitourinary
- Kidney abnormalities
- Irregular menstrual periods in females
- Undescended testicles in males
- Other male genitalia abnormalities
- Early prostate enlargement in males
Head and Facial Features
- Decreased head size
- Thick eyebrows that meet in the middle
- Long eyelashes
- Upturned nose
- Long smooth philtrum (the groove between the top of the lip and the bottom of the nose)
- Downturned corners of the mouth
- Small, recessed jaw, high, or cleft palate that can impact feeding
Neurological
- Seizures can occur
Skeletal System
- Short stature
- Smaller than average hands and feet
- Limb differences,
- Hip abnormalities
- Scoliosis
Vision problems /Hearing Loss
- Hearing Loss
- Multiple ear infections
- Visual impairment, often severe nearsightedness
