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Recurrence Rate
Pytanie
A parent asks...
The recurrence rate for families who have had a child with CdLS is 1.5%. That is about 1 in every 150 or so pregnancies for couples, who have already had a CdLS child, isn't it? Isn't the rate for the general population something like 1 in 10,000 to 30,000? How is it that the risk for families with CdLS becomes so much more likely? It is our understanding that the genetic abnormality that causes the syndrome is not "inherited" but, rather, a random mutation that occurs after fertilization. Do your recurrence rates suggest that there is something in the parents' genetic makeup that causes the recurrence rate to be so high? If not, why doesn't the rate stay the same for families with CdLS kids as it is for the general population? Dr. Jackson states: “The recurrence rate is about 1.5% providing you have examined parents for any suggestion of CdLS features and have found none.” Can you explain how the two sets of figures compare?
Odpowiedź naszych ekspertów
If either parent has any clinical sign of CdLS, then, based on our current understanding of the autosomal dominant gene mutation (changing in DNA of the gene) causing CdLS, they have a 50% chance of having another affected child. If neither parent has any sign of CdLS, the overall risk based on family studies is 1.5%. It is not zero because of the very rare occurrence of something called gonadal mosaicism in one of the parents. This is an entity in which the individual is carrying the mutated dominant gene in some of his or her gonadal cells (sperm or egg respectively) with all of the rest of the gonadal cells being "normal" (not carrying the mutated gene for CdLS). The initial diagnosis of CdLS was due to the gonadal cell carrying the change prior to conception, rather than the change occurring at conception from a single gonadal cell like MOST of the affected individuals. Since the parent has a small subpopulation of gonadal cells with the CdLS mutation, there is a slight risk that it could happen again. Thus, instead of 1 in 10,000 to 30,000 we have to say 1.5%, taking into account the few families who had more than one affected child with no sign in either parent. In other words, these few families have to have one parent with gonadal mosaicism who, by chance, used the gonadal cell with the CdLS mutation instead of the other "normal" cells for the subsequent child. These cases are extremely rare, so for each individual couple it is highly unlikely. Still, the number of 1.5% was based on all of the total children and siblings known at that point including those few families with more than one child and an unaffected parent. I would reassure the family that it would be extremely rare, and that ultrasound during the pregnancy can help reassure them if all looks good
TK 7-13-10
Zalecenie(a)
Familial recurrence risk
