Genetic Testing for the CdLS Spectrum (post birth)

Genetic Testing for the CdLS Spectrum (post birth)

Genetic tests have been developed to identify changes in any of the genes associated with the CdLS spectrum. A referral to a clinical geneticist can be made if parents feel that it would be useful to discuss the possibility of testing for the child with a CdLS spectrum syndrome. Genetic testing is not always appropriate or necessary (particularly if a doctor is very certain about the clinical diagnosis), but would be the only way to approach prenatal testing for future pregnancies.

Panel Sequencing

The most effective genetic test to identify a change in a gene known to cause CdLS is panel sequencing. Panel sequencing analyses multiple genes at once. When testing for CdLS spectrum the panel should include at least the seven known CdLS genes (see Figure 5 ). Most laboratories for genetic testing will include additional genes that can cause a phenotype resembling CdLS, such as CREBBP and EP300.

Sanger Sequencing

Although panel sequencing is the most effective genetic test, it may not be available in some parts of the world. Clinical geneticists may use other genetic tests, such as Sanger sequencing. Sanger sequencing uses a computer to look for gene mutations in a person’s DNA. If an individual has a classic CdLS phenotype, Sanger sequencing of the NIPBL gene is the preferred initial test. If an individual has a non-classic CdLS phenotype, other genes associated with the CdLS spectrum can be sequenced (R9).

Testing for Mosaicism

When a change in a gene associated with CdLS cannot be found using panel or Sanger sequencing, genetic testing can evaluate an individual’s DNA for mosaicism. Mosaicism is where there are different populations of cells which have a different genetic make-up in a single person. See the Mosaicism section.

Multiplex Ligation-dependent Probe Amplification

If genetic testing is not able to find mosaicism in an individual’s DNA, a test called multiplex ligation-dependent probe amplification (MLPA) can be considered. MLPA looks for deletions or duplications in the NIPBL gene.