Professional ballet dancers often have gene variants in their connective tissue

Relation

Vera AM, Peterson LE, Dong D, et al. High prevalence of connective tissue gene variants in professional ballet.Am J Sports Med. 2020;48(1):222-228.

Objective

To determine the prevalence of connective tissue gene variants in professional ballet dancers and to understand whether increased joint hypermobility or the presence of gene variants improved a ballet dancer's position within a company.

Draft

Cross-sectional study

Participant

This study included 51 adult male (n=26) and female (n=25) professional ballet dancers from a large metropolitan ballet company, 32 of whom completed genetic testing. Age ranged from 18 to 35 years with a mean of 23.9 years.

Study parameters assessed

The authors assessed all 51 participants for generalized joint hypermobility using a Beighton score, hip and ankle elective performance scores, and the Brighton criteria, a clinical tool that aids in the diagnosis of generalized joint hypermobility syndromes. Thirty-two participants agreed to genetic testing and were screened for 60 different connective tissue variants. These variants were grouped into the following clusters: Ehlers-Danlos syndrome (EDF); Marfan; Loeys-Dietz; Bethlem myopathy; and morphology of muscle, skeleton and connective tissue.

Primary outcome measures and key results

Of the 32 dancers who participated in the DNA analysis, 28 (88%) had at least 1 variant in the 60 genes tested. The researchers found a total of 80 variants. They found a variant in 26 of the 60 genes in at least one dancer. Brighton criteria were positive in 31.3% of participants and 53.1% had a positive Beighton score. No other connective tissue disease variants were found.

The authors found no advantage within the company (principal versus apprentice) for those with connective tissue variants. They found that dancers with variants in the Marfan and Loeys-Dietz clusters had reduced hip involvement.

comment

Inherited hypermobile spectrum disorders (HSD) are an increasing cause of chronic pain and multisystem dysfunction.¹This study contributes to defining the prevalence of previously unreported and underreported connective tissue variants. Researchers evaluated 8 genes that have never been reported or are reported to occur in <0.0001% of the population.

This data is amazing. Either these connective tissue gene variants are significantly more common than previously reported, or ballet dancers are significantly overrepresented, or both. This information can help physicians who suspect secondary causes of pain screen for underlying HSD by taking an appropriate history. It can be helpful for screening to simply ask your patients if they have done ballet, gymnastics, or cheerleading in the past.

There are many myths about HSD. For example, patients do not need a history of open joint dislocation to meet the 2017 diagnostic criteria for hypermobile Ehlers-Danlos syndrome (hEDS), or HSD.²Clinicians may overlook HSD in their differential in patients with chronic pain due to the perceived rarity of these disorders. Twenty years ago a prevalence of 1/5,000 (0.0002%) was reported,³and more recent studies give it in 1/500 (0.002%).⁴The true prevalence is unknown due to lack of recognition and application of appropriate diagnostic criteria. This inadequate understanding has led to increased patient suffering and misdiagnoses such as fibromyalgia, central pain sensitization and/or psychiatric disorders.⁵

This study is significantly limited by the lack of an age-matched control population. Age-matched controls could have helped define whether underreported variants are truly overrepresented in ballet dancers. While it is impressive that 88% of participants had an identifiable variant, many of the most common variants are not reported in the Human Gene Mutation Database or Ensembl, and therefore we have no way of knowing whether these variants are significantly higher compared to a non-Ballet population. For example, the most commonly identified variant was the TTN gene, which is involved in muscle morphology. This variant has been found 22 times, but the frequency in the general population is unknown. In addition, data on ethnicity is not recorded, which is likely to impact the frequency of variants.

This data is amazing. Either these connective tissue gene variants are significantly more common than previously reported, or ballet dancers are significantly overrepresented, or both.

Unfortunately, the authors did not report or analyze the patients in whom >1 variant was present. This was probably due to the small sample size. For example, they found 3 variants at theTNXBGen, 2 at theADAMTS22 onCOL1A2and 1 atCOL1A1. These are each associated with the following forms of Ehlers-Danlos syndrome: classic-like, dermatosparaxis, valvular and classic. The authors should have performed echocardiograms on all dancers who had Marfan, EDS, or Loeys-Dietz genes. The authors do not comment on whether these dancers with known EDS variants would be more likely to meet the Brighton criteria. If this information had been reported, it could help us better understand these diseases. This is likely present in their data but is not reported.

This study used the outdated 1998 Brighton criteria to identify participants with hypermobile disorder.⁶The Brighton Criteria were replaced in 2017.⁷The Brighton criteria have previously been used to identify patients with benign joint hypermobility syndrome (BJHD). We no longer use this terminology, and this disorder is now called hypermobile spectrum disorder (HSD), which includes hypermobile Ehlers-Danlos syndrome (hEDS).

Additionally, researchers did not use validated outcome measures to assess chronic pain. Although hypermobility can have benefits - for example, improved performance in a discipline that requires excessive joint movements like ballet - it is important to understand that it can have debilitating consequences.^8.9

Based on clinical experience with more than 1,000 HSD patients, I suspect that more severely affected patients may be more severely affected due to severe pain, joint instability, injury, and the presence of other comorbid conditions, such as: POTS) or mast cell activation syndrome (MCAS).^10,11

Researchers are still elucidating the true frequency of these overlapping comorbidities, but there is increasing evidence that disability is greater in patients with multisystem diseases.¹²Doctors must understand that these disorders can lead to global disability. Integrative medicine is well positioned to help these patients improve joint stability and autonomic nervous system and immune system function if the practitioner is willing to delve deeply into the literature.

Conclusion

Overall, this study improved our understanding of hypermobile connective tissue gene variants. Future studies need to include adjusted controls to define the true incidence in ballet dancers compared to the general population. This work ultimately fails to support their hypothesis that variants within hypermobility-associated genes would be overrepresented in professional ballet dancers. We also need to examine dancers' ethnicity, validated pain scales, and quality of life. Current diagnostic criteria and nomenclature of hypermobile spectrum disorders and hypermobile Ehlers-Danlos syndrome should be used. While this study did not compare the prevalence of HSD with age-matched controls, clinicians should still consider asking their patients with chronic pain about previous ballet, gymnastics, and cheerleading participation.