Fertility Among Those With Chromosome 18 Duplications or Deletions
The data regarding fertility for people with chromosome 18 abnormalities is rarely discussed, yet it is critically important. Knowledge about fertility potential can help the individuals with chromosome 18 abnormalities and their families make informed decisions about potential life choices. The data presented here include only those individuals who actually have a chromosome 18 deletion or duplication. It does not included data from people with balanced translocations without a deletion or duplication themselves. It also does not include data from individuals who are mosaic for their chromosome 18 condition, which adds a separate layer of complexity to the issue. The data presented here are gathered form the medical literature and from the study participants at the Chromosome 18 Clinical Research Center who have a chromosome 18 deletion or duplication.
Also, these data only address the biological possibility of being a mother or father. This is an entirely separate and unrelated issue from an individual’s ability to be a good parent.
18p+
There are very few fertility reports of people with 18p duplications. The majority of those individuals had duplications of the entire 18p short arm. Many of those reports include individuals who were not identified as having an 18p duplication until after they had a child, or when a family member was diagnosed because the child or family member had medical or developmental issues. In other words, there was no reason to suspect they had a chromosome abnormality, yet they had 18p+. This also implies that their child or other family member with the same 18p duplication did have medical issues that prompted a genetic evaluation.
- With regard to females, four mothers are reported, which means there is fertility potential.
- With regard to males, one male was unable to produce sperm (azoospermia) and a second was married and involuntarily childless. There are two fathers with 18p+ reported in the literature, however they each had very small duplications involving only a couple of genes as opposed to the others who had duplications of the entire short arm, which includes 67 genes. Therefore, for the males with a full 18p duplication, no children have been reported meaning there is a strong suspicion of infertility.
18p-
Many individuals with 18p- have been reported in the literature. Additionally there are 139 individuals with 18p- enrolled at the Chromosome 18 Clinical Research Center, however the majority have not yet reached a reproductive age.
- With regard to females, there are 11 who are mothers, some of whom have a deletion of the entire short arm of the chromosome. This indicates that there is indeed reproductive potential for females with 18p-.
- With regard to males, none of the participants have been reported to be fathers and there are no reports of males fathering children in the literature.
18q+
Duplications of 18q are very rare and are highly variable in their size and location along the chromosome 18 long arm. This makes it difficult to arrive at any conclusions in terms of fertility.
- With regard to females, there is one report of a mother who had a terminal 18q duplication of approximately ¼ of the long arm of the chromosome.
- With regard to males, there are no reports of any fathers with an 18q duplication. There is a report in the literature of a male with a duplication of terminal 18q (just slightly larger than the Reference Group region) who had typical development except for being infertile due to low sperm motility.
Proximal 18q- (very rare)
Again, proximal 18q- is very rare with only about a dozen cases reported in the literature and 20 individuals enrolled at the Chromosome 18 Clinical Research Center.
- With regard to females, only one mother has been identified even though all but one of the cases are beyond puberty.
- With regard to males, there are no fathers either in the literature or in our cohort although most participants are of reproductive age.
Distal 18q- (384 participants)
This is by far the largest group with many individuals reported in the medical literature and 384 participants enrolled at the Chromosome 18 Clinical Research Center. But again, the Research Center Cohort is relatively young with many of participants too young for reproductive potential.
- With regard to females, there are eleven participants who are mothers. Some of their children also have 18q- while others have normal chromosomes.
- With regard to males, one is known to have an abnormally low sperm count (oligospermia) and another unable to produce sperm (azoospermia). There is another male who has fathered children, however, he has a small interstitial deletion of distal 18q. Therefore, no males with a terminal 18q deletion have fathered children.
There are no reports of either males or females with Trisomy 18 or Tetrasomy 18p who have reproduced.
Regarding all these conditions, the lack of data does not mean affected individuals are infertile and that families do not need to concern themselves with the possibilities of reproduction. Many individuals included in the studies may simply never have had the opportunity or may have been using birth control, hence their fertility is still unknown. For males, the fertility potential is testable, and the families can consult with their primary care doctor to request this type of testing. In discussing fertility amongst those living with chromosome 18 conditions, families should be aware that individuals with diminished decision-making capacity could be easily be taken advantage of. Likewise, individuals with executive function limitations may have issues with impulse control. These factors mean it is important for families to understand their loved one’s potential for reproduction and assist them with making informed and wise choices.
As far as the specific gene deletions or duplications on chromosome 18 that might affect fertility, there are only two candidate genes with a potential role in male infertility. One of these genes is in a region of the chromosome close to the centromere. At present, there is no documented case of an individual that has this type of deletion. The other gene is nearby the first, and there has only been one documented case of an individual with this deletion. In both cases, these genes are only duplicated in someone with full Trisomy 18. It is therefore yet to be understood why so many males with chromosome 18 conditions appear to be infertile.
We are always expecting to learn more as the study participants get older, and this is one reason why the Chromosome 18 Clinical Research Center’s work is ongoing as a lifetime longitudinal study. It is imperative that that individuals and families enrolled as research study participants continue to send us copies of any relevant medical records so we can follow participants’ development over the course of their lifetimes to learn more about how the chromosome 18 conditions impact key aspects of life, such as fertility.
