If a child is found to have Phelan-McDermid syndrome and parents' genetic testing is normal, what is the chance for parents to have another child with Phelan-McDermid syndrome?
If a child is found to have Phelan-McDermid syndrome and the parents' genetic testing results are normal, the chance to have another child with Phelan-McDermid syndrome is likely very low (< 1%). However, there has been a reported case of a mother who did not have Phelen-McDermid syndrome but who had two children with Phelan-McDermid syndrome. It is suspected that some of her egg cells had the chromosome 22 deletion and other egg cells that had normal chromosomes. Having some egg cells (or sperm cells in males) with a genetic change and others that are normal is called germline or gonadal mosaicism. Germline mosaicism can rarely able to be detected through standard genetic blood tests. If a parent has some egg cells or some sperm cells with a chromosome 22q13.3 deletion, their chance to have more children with Phelan-McDermid syndrome is increased, but the exact recurrence risk depends on the number of egg or sperm cells with the deletion. If ALL the egg or sperm cells have the chromosome 22q13.3 deletion, then all biological children would be predicted to have Phelan-McDermid syndrome; however that would very, very rare as it would mean that every precursor cell to the egg or sperm would have had to have both chromosome 22s with 22q13.3 deletions. If half of the egg or sperm cells have the chromosome 22q13.3 deletion, then the risk would be up to 50% chance to have a baby with Phelan-McDermid syndrome. In general, if there is germline mosaicism, the risk for another child with Phelan-McDermid syndrome may be low (around 1%), moderate (as in 6%), or high (up to 50%), depending on both the proportion of egg or sperm cells with the chromosome 22 deletion and the number of embryos with the chromosome 22 deletion that implant, grow, and develop successfully.
If a couple has had one child with Phelan-McDermid syndrome and is concerned about the risk to have another child with this syndrome, it can be very useful to speak with a genetic counselor in their area to learn more about the recurrence risk to have another baby with Phelan-McDermid syndrome, germline mosaicism, and preconceptional/prenatal testing options.
SOURCE: Emory University - Department of Human Genetics in collaboration with ThinkGenetic • https://www.thinkgenetic.com/diseases/606232-phelan-mcdermid-syndrome-100/overview/6969 • DATE UPDATED: 2016-11-25
Tabolacci E, Zollino M, Lecce R, Sangiorgi E, Gurrieri F, Leuzzi V, Opitz JM, Neri G. Two brothers with 22q13 deletion syndrome and features suggestive of the Clark-Baraitser syndrome. Clin Dysmorphol. 2005;14:127-32. PMID:15930901
Baylor College of Medicine Parental Mosaicism Recurrence Risk Calculator http://www.recurrencerisk.org/
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