Hypermobile Ehlers–Danlos syndrome: A review and a critical appraisal of published genetic research to date

The Ehlers–Danlos syndromes (EDS) are a collection of rare hereditary connective tissue disorders with heterogeneous phenotypes, usually diagnosed following clinical examination and confirmatory genetic testing. Diagnosis of the commonest subtype, hypermobile Ehlers–Danlos Syndrome (hEDS), relies so...

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Bibliographic Details
Published in:Clinical genetics 2022-01, Vol.101 (1), p.20-31
Main Authors: Scicluna, Kirsty, Formosa, Melissa M., Farrugia, Rosienne, Borg, Isabella
Format: Article
Language:English
Subjects:
Biomedical Research - trends
Classification
Collagen
connective tissue diseases/genetics
Connective tissues
Diagnosis
Disease Management
Ehlers-Danlos syndrome
Ehlers-Danlos Syndrome - diagnosis
Ehlers-Danlos Syndrome - etiology
Ehlers–Danlos syndrome type 3
Genetic Association Studies - methods
Genetic Predisposition to Disease
Genetic screening
Humans
hypermobile EDS
Phenotypes
Tenascin
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Description
Summary:The Ehlers–Danlos syndromes (EDS) are a collection of rare hereditary connective tissue disorders with heterogeneous phenotypes, usually diagnosed following clinical examination and confirmatory genetic testing. Diagnosis of the commonest subtype, hypermobile Ehlers–Danlos Syndrome (hEDS), relies solely on a clinical diagnosis since its molecular aetiology remains unknown. We performed an up‐to‐date literature search and selected 11 out of 304 publications according to a set of established criteria. Studies reporting variants affecting collagen proteins were found to be hindered by cohort misclassification and subsequent lack of reproducibility of these genetic findings. The role of the described variants affecting Tenascin‐X and LZTS1 is yet to be demonstrated in the majority of hEDS cases, while the functional implication of associated signaling pathways and genes requires further elucidation. The available literature on the genetics of hEDS is scant, dispersed and conflicting due to out‐dated nosology terminology. Recent literature has suggested the role of several promising candidate mechanisms which may be linked to the underlying molecular aetiology. Knowledge of the molecular genetic basis of hEDS is expected to increase in the near future through the mainstream use of high‐throughput sequencing combined with the updated classification of EDS, and the upcoming Hypermobile Ehlers–Danlos Genetic Evaluation (HEDGE) study.
ISSN:0009-9163
1399-0004
DOI:10.1111/cge.14026