Hypermobile ehlers-danlos syndrome Q79.6

Ehlers-Danlos Syndrome (EDS) is a heterogeneous group of hereditary connective tissue diseases whose main clinical features are overstretchability of the skin and hyperreflexia of the joints. Depending on the type of disease and the underlying gene mutations, vessels, muscles, ligaments, tendons and internal organs are also affected.

So far, 19 gene mutations are known to trigger EDS. The various mutations lead to changes in the structure, production or processing of collagen or of proteins that interact with collagen. The frequency of occurrence in the population is assumed to be 1:5,000 to 1:10,000, making EDS a rare disease (orphan disease).

Hypermobile EDS (formerly type III) is a very rare, autosomal-dominantly inherited variant of the EDS family, which is characterized by a conspicuous hypermobility of the joints. The genetic cause is not yet known. The diagnosis will be made clinically after thorough examination (Tinkle B et al. 2017).

The hEDS is characterized above all by hypermobility of large and small joints. Subluxations and luxations can occur regularly. Those affected often suffer from joint instability and often have soft, velvety skin that can be easily damaged. Very often patients suffer from chronic pain. The severity can be moderate to very severe. About 90% of EDS sufferers have chronic pain, with the highest pain scores found in hEDS patients (Chopra et al.2019). Symptoms are not grouped according to major and minor criteria, but rather in 3 groups with criteria 1-3:

• Criterion 1: generalized hypermobility of the joints
• Criterion 2: This is composed of 3 clusters of characteristics (5 symptoms are a prerequisite):
  • A: soft velvety skin, slight hyperelasticity, in youth increased striae in parts of the body not exposed to mechanical stress, pulled nodules, atrophic scars on 2 parts of the body, abdominal hernias, bladder floor, rectum or uterus prolapse without other causes, arachnodactyly, marfanoid habitus, mitral valve prolapse, aortic root dilatation, toothache and high narrow palate
  • B: positive family history
  • C: chronic musculoskeletal pain, chronic pain, recurrent joint dislocation
• Criterion 3: Absence of marked skin fragility; exclusion of other (connective tissue) diseases or diseases with joint hypermobility

1. Brady A et al (2017): Ehlers-Danlos syndrome, rare types. In: Ehlers-Danlos Society. American Journal of Medical Genetics 175C:70-115
2. Brinckmann J (2018) Hereditary connective tissue diseases. In. Plewig et al. (Ed.) Braun-Falco`s Dermatology, Venerology and Allergology, Springer Reference Medizin S 883-890
3. Bowen et al (2017): Ehlers-Danlos syndrome, classical type. American Journal of Medical Genetics 175C:17-39
4. Byers PH et al (2019): Diagnosis, natural history and management in vascular Ehlers-Danlos syndrome. American Journal of Medical Genetics 175C:40-47
5. Chopra P et al (2017): Pain management in the Ehlers-Danlos syndromes. American J
6. Tinkle B et al (2017) Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and naturalhistory. At J Med Genet C Semin Med Genet 175:48-69.
7. Micale L et al (2019) Novel TNXB Variants in Two Italian Patients with Classical-Like Ehlers-Danlos Syndrome. Genes (Basel) 10: doi: 10.3390/genes10120967.