In other families that went on to have other children after having one child with CdLS, how many were again affected by CdLS? A random mutation implies that every pregnancy has the same likelihood of producing a child with CdLS, but are families at a higher risk for another random mutation?
The random mutation is the most likely theory of the cause of CdLS to the best of our current knowledge. If someone has a one in 30,000 chance (for example) of having a spontaneous mutation causing CdLS in one pregnancy, then it still should be that same chance with the next pregnancy. Thus, the chance of having it happen twice, if it was due to a spontaneous mutation, should be 1/30,000 x 1/30,000, or rare enough not to recur below 1%. However, one parent could be carrying the mutation (a dominant mutation) in some of their egg or sperm cells (without their knowledge) and pass it on in that way. Since they themselves are not affected, the risk should not be 50%, but it would be higher than below 1%. Then there is still the chance that CdLS is due to a recessive mutation, in which each parent has to be carrying one abnormal mutation in the gene on one chromosome (but have a normal gene on the matching chromosome); in which case the chance for each parent to pass the mutation on to a pregnancy is ½, and the risk for each pregnancy is ½ x ½ or ¼. Since we don’t know which of any of these theories is correct, we use the overall 1.5% (or so) recurrence risk that Dr. Laird Jackson calculated when he added up all of the affected children, siblings and pregnancies. (American Journal of Medical Genetics 47:940-946, 1993). I also always encourage families to have a high-resolution prenatal ultrasound .
Since any subsequent pregnancy is potentially at risk for another fetus with CdLS, the following would be justified to follow: Perform high resolution ultrasounds, monitor for growth retardation, limb differences or possible diaphragmatic hernia, consider a fetal echocardiogram to rule out any structural heart differences, measure nuchal fold thickness in the first trimester, and check a PAPP-A level in the second trimester.
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