'Why are people affected so differently?

At the beginning of the previous section (Genetics), we noted that describing the inheritance patterns of hEDS using what is known as a ‘classic’ or ‘simple genetics’ model is probably too simplistic. In fact, to fully understand the whole range of variations seen in the spectrum spanning joint hypermobility, through hypermobility spectrum disorders and hEDS, it is likely that geneticists will need to look towards a slightly more complex model, which allows for the expression of the single or multiple gene mutation(s) to be further influenced by other genetic, environmental, or constitutional factors. 

The Threshold Model

The potential influence of genetic, environmental or constitutional factors may be better explained using the ‘Threshold Model’ - whereby a single, highly penetrant, dominant, inherited gene mutation is considered to increase risk, but is not necessarily sufficient for the disorder to be expressed (for symptoms to show). The underlying connective tissue variant seen in the hEDS/HSD spectrum can vary in severity and is not always sufficient per se in causing the disorder outright but, when other genetic, environmental, or constitutional factors are added, the combination may be sufficient to reach the threshold for disease expression in a hypermobile person.  These factors impact on how specific segments of the genetic code are turned on or ‘expressed’ and whether, when, and how the process happens (1 & 2).  

Examples of environmental and constitutional factors include:

• An individual’s ethnicity 

• Their biological sex 

• Age(ing)

• The combination of hypermobility types inherited (see Box 5 below)

• The physical character of an individual (build, strength, general health etc.)

• Psychological characteristics

• Sports activities they may pursue 

• Dietary habits

• Traumas and/or surgeries they undergo 

• Periods of temporary immobility

• How well an individual's brain interprets proprioceptive feedback

In this section, we will take a look at some of the above factors, which may contribute to the variation in manifestations and severity, in more detail:

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Ethnic background 

People of different ethnic backgrounds have differences in their joint mobility, which may reflect differences in the structure of the collagen proteins. Hypermobility is more common in those from Asian  backgrounds, African Black populations (3) and those from Indian heritage, than in white Caucasians. For example, people from the Indian sub-continent often have much more supple hands than Europeans (4).

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