Cornelia De Lange Syndrome (CdLS) is a genetic condition which affects around 1 in every 10,000 live births. Individuals affected have the condition when born, but sometimes it is not diagnosed until later. This is because there is a wide variety of physical, cognitive and medical symptoms, and the effects can range from mild to severe, making diagnosis difficult. CdLS is also sometimes known as Brachman De Lange Syndrome, Bushy Syndrome, or Amsterdam Dwarfism.
Although CdLS has a genetic cause, it is not passed on by the parents, and siblings are unlikely to be affected, although occasionally more than one child in a family is diagnosed. It affects boys and girls equally, and can occur in any ethnic background or race.
Cornelia De Lange Syndrome was first noted in 1916, but was identified as a syndrome by the Dutch paediatrician Cornelia De Lange in 1933, which is why it is named after her. It is referred to as a syndrome because there is a range of features and characteristics associated with it; individuals with CdLS may have only a few or all of the symptoms.
There are are many features and characteristics associated with CdLS. The most common are:
CdLS is caused by a genetic mutation on the 5th chromosome, which occurs at a critical stage in early foetal development. So far, three genes have been shown to be involved, although others may yet prove to be affected as well.
There are four SMC genes, which are essential in ensuring correct chromosomal development in the early stages of pregnancy. Defects in two of these (SMC1A and SMC3), can affect CdLS.
In 2004, Researchers in Newcastle on Tyne and at the Children's Hospital of Philadelphia discovered that a mutation on a NIPBL gene led to Cornelia De Lange Syndrome. The NIPBL gene produces delangin, which is important to the correct holding together of chromosomes during foetal development, ensuring chromosomes reach the right density, and affects the way DNA identifies and repairs damage. Over 50% of those diagnosed have a mutation on this NIPBL gene, whilst the incidence on the SMC genes is much lower.
Because of the wide variety of characteristics and features, CdLS is usually clinically diagnosed by specialists. This will involve taking a medical history, carrying out a medical examination and arranging genetic testing (especially for mutations in the NIPBL gene). Although genetic mutations are identified in around 60% of cases, sometimes tests do not show them. However, this is believed to be because there are other genes involved in CdLS which have not yet been isolated, so once these have been identified and confirmed, genetic testing can include them.
Pre-natal diagnosis of CdLS is difficult, because of the range of factors involved. If a child is born with CdLS, it is recommended to the parents that a high definition ultra-sound scan is carried out during the 18th week of any subsequent pregnancy. This can focus on observable features such as limb abnormalities and heart defects, but cannot provide a definitive pre-natal diagnosis.
The CdLS Foundation of UK and Ireland is a voluntary organisation which is part of a network of similar organisations around the world. It plays a vital role in supporting parents, advocating research, and raising awareness amongst health professionals to encourage early diagnosis.
The CdLS Foundation has a vast range of resources to support families. There is a helpline staffed by volunteers, and it has produced booklets and information packs giving important information for families and health professionals. The quarterly newsletter discusses relevant issues, and contains updates about the latest research. Family meetings are held every six months, to allow families affected to meet together and share experiences, and is held in different locations to enable maximum attendance. Major conferences are also arranged, including international attendance, and there are also ‘mini conferences' at other times.
The CdLS Foundation has established its own Scientific Advisory Council (SAC), which exists to allow professionals to share information, liaise with each other (for example, by attending international conferences), and to give families access to accurate scientific information about CdLS.
The CdLS Foundation also support medical research in the bid to improve the diagnosis and treatment of individuals with CdLS, and to look for a cure. However, as the organisation is reliant on voluntary donations, funds are limited.
Naturally, a diagnosis of CdLS has a significant impact on families, and the variety of features and characteristics mean that each person must be supported and treated individually. However, research is continuing, and organisations such as the CdLS Foundation can offer help and support both to those directly affected, and to health professionals working in this field.