MRC HGU Cornelia de Lange Syndrome Study

 

David R FitzPatrick MD, FRCP • Andrew Jackson PhD, MRCP
 

Download UK Consent and Information Forms

 

 

Background

CdLS is a rare developmental malformation syndrome characterized by learning disability, small stature, limb abnormalities, severe gastroesophageal reflux and distinctive craniofacial features. Within Cornelia de Lange syndrome there is a wide spectrum of severity. I have been the medical director of the Cornelia de Lange syndrome (CdLS) Foundation http://www.cdls.org.uk/ since 2002.   In the north of England the incidence of Cornelia de Lange syndrome of 1 in 37,000 (Dr. M. Ireland, personal communication). It is suspected that there are many mildly affected individuals who remain undiagnosed.

 

It is possible to identify the genetic cause in about 50% of CdLS cases.  Most of the genetic changes are in a gene called NIPBL on chromosome 5.  These mutations are mostly found in the affected individuals but not in either parent. Such mutations are called de novo. Mutations have also been identified in a small number of cases in SMC1A on the X chromosome and SMC3 on chromosome 10. 

In 50% of cases the genetic cause of the disorder is not known.

 

Download UK Consent Forms

Consent Forms

Genetic disorders of brain development info sheet (Word File)

Child consents brain development2 (Word File)

Adult patient info sheetv2 genetic disorders of brain development (Word File)

Adult incapacitated consents brain development2  (Word File)

Adult consents brain development2 (Word File)

 

 

 

 

These fall into three parts:

1. The Eye Malformation Study (information and consent forms)
2. The Facial Cleft Study (information and consent forms)
3. Cornelia de Lange Syndrome Study
   (this page)

 

 

Aims of this Study

1. To collect DNA samples from a large number of Cornelia de Lange Syndrome (CdLS) cases
2. To look for mutations in the known CdLS genes:

   a. NIPBL
   b. SMC1A
   c. SMC3 

3. To look for mutations in new “candidate” genes to explain the 50% of cases who do not have mutations in the known genes.

Who is Eligible for the Study?

Any case of CdLS in the UK in whom the diagnosis has been confirmed by a consultant clinical geneticist with an interest in dysmorphology

 

What the Study Involves?

1. DNA will be obtained from affected individuals using a new technique that collects saliva samples with a small “sponge on a stick” that is placed under the tongue.
2. Where possible we will also collect DNA from both parents using saliva samples