What Autosomal Dominance Means For You If You Have HSD/hEDS
As I explained in a previous post, it’s really important that we think carefully about what we’re referring to when we use the term “hypermobility.” You can read “What is Hypermobility? Hypermobility vs Hypermobility Spectrum Disorder vs Hypermobile Ehlers Danlos Syndrome” HERE
Today we’ll be talking specifically about Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD). The other kinds of EDS and other kinds of connective tissue disorders will be discussed in a separate post.
Genetic Inheritance of hEDS and HSD
There is clear agreement that hEDS is inherited in what is referred to as an autosomal dominance pattern (more on that in a minute).
However, at present there is a lack of consensus on the inheritance pattern of HSD. The Ehlers-Danlos Society states:
“The cause(s) of HSD have not been identified. Currently, we do not know if HSD is a genetic disorder. We do know that joint hypermobility tends to run in families, but not everyone with joint hypermobility has a type of HSD. More research is needed to better understand the cause(s) of HSD.”
However, there are researchers who disagree with that perspective. For example the paper Diagnosis and Management of Hypermobility Spectrum Disorders published in The Journal of the American Board of Family Medicine states that,
“HSDs have a strong genetic basis but no known genetic markers. The vast majority of cases do not seem to be linked to any identifiable mutation, although pedigree studies have shown a weak autosomal dominant inheritance pattern with variable penetrance.” (Atwell et al., 2021)
My personal view is that HSD, like hEDS, is autosomal dominant. I am not a researcher or a geneticist, but based simply on the amount of patients I see at clinic with diagnosed HSD I believe it’s unlikely to follow a recessive inheritance pattern (as I would then see fewer cases of it, like other recessively inherited connective tissue disorders). This is purely anecdotal, and just my personal view.
The seemingly high prevalence of HSD that I see in clinic might also be partially explained by issues with the current hEDS 2017 Diagnostic Criteria. My personal view is that it misses cases of hEDS (especially those in patients who have more pronounced hypermobility in their lower extremities due to issues with the Beighton Scale/Criterion 1).
In conclusion: everyone agrees that hEDS is autosomal dominant, and there is some disagreement over whether or not HSD is.
But We Don’t Know the Gene for hEDS. So How Do We Know For Sure That It’s Autosomal Dominant?
We know for sure that hEDS is autosomal dominant due to a kind of study called a pedigree study. In a pedigree study, researchers look at how a trait (note that I have said a trait such as hypermobility, and not a gene!) is inherited or not inherited within a genetically related family of individuals.
What is Autosomal Dominance?
Let’s start with defining our terms.
Autosomal = gene in question is located on one your numbered chromosomes (as in, NOT your X/Y chromosomes)
Dominant = if you have a single copy of the gene then you have the condition (unlike autosomal recessive disorders where you need TWO copies of the gene to have the condition.
So autosomal refers to the location of the gene, and dominance refers to the inheritance pattern of “you just need one.”
Quick note: many people (myself included) think it’s likely that hEDS and HSD will ultimately be found to be conditions where more than one mutated gene is present. But to keep this post simple we’re going to pretend like hEDS is caused by just one mutated gene.
Here’s a simple diagram to illustrate autosomal dominance:
Diagram showing autosomal dominant inheritance of hEDS when only one parent is affected
In simple terms: if you have hEDS then every time you have a biological child there is a 50% chance that the child will inherit the gene/genes linked to hEDS.
Is hEDS Sex-Linked?
No, hEDS is not sex-linked (you are not more/less likely to get it if you are XY/XX). This means that a XY child and a XX have an equal chance of having hEDS from a genetic perspective.
However, current research suggests that males only make up <30% of people with diagnosed hEDS (despite making up 50% from a genetic perspective).
Although this difference may be due to issues with diagnosis and identification, researchers generally agree that this difference in presentation in males vs females is likely due to higher levels of testosterone in males and general differences in hormonal milieu.
What Happens if Both Parents have hEDS?
I mention this because I cannot tell you how often I see patients who are couples in romantic relationships where both parents have hEDS. My personal view is that the commonality of experience combined with the correlation with neurodivergence (I can’t currently find any research for this, but I have spoken with ADHD experts who believe that people with ADHD in particular seem to end up in relationships with each other) makes people with hEDS attracted to each other.
Again, I want to stress that I have NO proof for this. This is purely my personal and anecdotal view.
In the situation where both parents have hEDS, the inheritance diagram would look like this:
Diagram showing autosomal dominant inheritance of hEDS when both parents are affected.
In simple terms: this means that every time this couple reproduce and have a child there is a 75% chance that the child will inherit the gene(s) that are linked to hEDS.
Should People with hEDS Not Have Biological Children?
This is a really complex question that you need to discuss directly with your trusted and qualified healthcare provider. Some questions to ask yourself and/or your healthcare provider might include:
- how could carrying a pregnancy/the demands of parenthood affect my health?
- are there any ways that we could reduce the risk of harm during pregnancy/childbirth/postpartum?
- can I access specialist support?
- do I have access to financial support and care support should I need it?
- am I prepared for the risk that my child’s symptoms might be more serious than mine/my partner’s?
- am I prepared for the risk that my symptoms could get worse in future (even though they are well-managed at present)?
I also often get asked by patients if there are any ways to genetically screen embryos for hEDS. The short answer is no, as we do not know the gene(s) there are currently no specific genetic screening tools for hEDS. However, the long answer becomes is this something that we want to do? Is selecting against an embryo with hEDS an ethical decision to make? This gets into a whole discussion regarding eugenics, and the reality is that at some point the hypermobile community will likely have to discuss this more openly as genetic screening tools continue to advance.
As someone who is hypermobile myself, my personal view is that I’m happy to be here and I’m very lucky to enjoy a great quality of life. But that in part is undboutedly due to environmental factors.
Why Not Everyone with hEDS Has the Same Symptoms: Genotype vs Phenotype
As you probably know by now, there are MANY different ways in which hEDS and HSD can present in individuals. In fact, this variable presentation is why many people in this community consider hEDS and HSD to be a spectrum.
Genotype = your genes (your literal DNA code)
Phenotype = the physical expression/manifestation of your genes. What they mean in terms of your lived experience of your body.
One thing that can greatly influence how hEDS and HSD affect someone is their environment. However, I mean environment in a very broad sense. I’m thinking of. . .
- hormones
- nutrition
- access to healthy/safe forms of exercise
- good general medical care/healthcare support
- early diagnosis/identification
- support from family/friends
- financial resources
- etc.
My clinical work becomes really hard if I’m not optimistic for the future. My hope is that with greater awareness we will see earlier identification and earlier support for people with HSD, hEDS, and other forms of hypermobility. Although having all of the best environmental factors possible will not magically fix anyone’s connective tissue, what it will do is give them the highest quality of life possible given the limitations of their connective tissue. Imagine a world where every healthcare provider and workplace and school knows what HSD/hEDS are, and understand (and are willing) to support the people in those environments.
I know it’s not the world we live in right now, but it’s my hope that it can be the world we get to see in the future.
In Conclusion. . .
- hEDS is autosomal dominant. If one parent has hEDS then there is a 50% chance that a given child will have hEDS. If both parents have hEDS then there is a 75% chance that a given child will have it.
- there are MANY things to consider if you’re someone with hEDS who is thinking of having a biological child. Please speak with your healthcare provider directly about this. It’s really important!
- your genotype does not directly determine your phenotype. Keep doing your own research (and speak with your healthcare providers) on ways in which you can positively affect your health by improving environmental factors. Check out my podcast Help! I’m Hypermobile for a lot more info on this.
Works Cited
- Atwell, K., Michael, W., Dubey, J., James, S., Martonffy, A., Anderson, S., Rudin, N., & Schrager, S. (2021). Diagnosis and Management of Hypermobility Spectrum Disorders in Primary Care. Journal of the American Board of Family Medicine : JABFM, 34(4), 838–848. https://doi.org/10.3122/jabfm.2021.04.200374
- Kumar, B., & Lenert, P. (2017). Joint Hypermobility Syndrome: Recognizing a Commonly Overlooked Cause of Chronic Pain. The American journal of medicine, 130(6), 640–647. https://doi.org/10.1016/j.amjmed.2017.02.013
- Castori, M., Sperduti, I., Celletti, C., Camerota, F., & Grammatico, P. (2011). Symptom and joint mobility progression in the joint hypermobility syndrome (Ehlers-Danlos syndrome, hypermobility type). Clinical and experimental rheumatology, 29(6), 998–1005.
- Demmler, J. C., Atkinson, M. D., Reinhold, E. J., Choy, E., Lyons, R. A., & Brophy, S. T. (2019). Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case-control comparison. BMJ open, 9(11), e031365. https://doi.org/10.1136/bmjopen-2019-031365
- Schubart, J. R., Mills, S. E., Schaefer, E. W., Bascom, R., & Francomano, C. A. (2022). Longitudinal analysis of symptoms in the Ehlers-Danlos syndromes. American journal of medical genetics. Part A, 188(4), 1204–1213. https://doi.org/10.1002/ajmg.a.62640
- Castori, M., Camerota, F., Celletti, C., Grammatico, P., & Padua, L. (2010). Ehlers-Danlos syndrome hypermobility type and the excess of affected females: possible mechanisms and perspectives. American journal of medical genetics. Part A, 152A(9), 2406–2408. https://doi.org/10.1002/ajmg.a.33585
- Castori, M., Morlino, S., Celletti, C., Ghibellini, G., Bruschini, M., Grammatico, P., Blundo, C., & Camerota, F. (2013). Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. American journal of medical genetics. Part A, 161A(12), 2989–3004. https://doi.org/10.1002/ajmg.a.36315
