Hereditary alpha-tryptasemia modifies clinical phenotypes among individuals with congenital hypermobility disorders

Maribel Vazquez, Jack Chovanec, Jiwon Kim, Thomas DiMaggio, Joshua D. Milner, Clair A. Francomano, Christina A. Gurnett, Marco Ritelli, Marina Colombi, Jonathan J. Lyons

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Hereditary alpha-tryptasemia (HαT) is an autosomal dominant (AD) genetic trait characterized by elevated basal serum tryptase ≥8 ng/mL, caused by increased α-tryptase-encoding TPSAB1 copy number. HαT affects 5% to 7% of Western populations and has been associated with joint hypermobility. Hypermobility disorders are likewise frequently AD, but genetic etiologies are often elusive. Genotyping of individuals with hypermobility spectrum disorder (n = 132), hypermobile Ehlers-Danlos syndrome (n = 78), or axial skeletal abnormalities with hypermobility (n = 56) was performed. Clinical features of individuals with and without HαT were compared. When analyzing our combined cohorts, dysphagia (p = 0.007) and retained primary dentition (p = 0.0003) were significantly associated with HαT, while positive associations with anaphylaxis (p = 0.07) and pruritus (P = 0.5) did not reach significance likely due to limited sample size. Overall, HαT prevalence is not increased in individuals with hypermobility disorders, rather linked to a unique endotype, demonstrating how HαT may modify clinical presentations of complex patients.

Original languageEnglish
Article number100094
JournalHuman Genetics and Genomics Advances
Issue number2
StatePublished - Apr 14 2022


  • EDS
  • HSD
  • HaT
  • TPSAB1
  • alpha-tryptase
  • connective tissue


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