Classical-like 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).

Classical like Ehlers-Danlos syndrome is an extremely rare form of Ehlers-Danlos syndrome (<30 people have been described so far - Micale L et al. 2019), which is phenotypically similar to Classical EDS but without the atrophic scarring characteristic of this type.

The genetic cause of Classical-like EDS is a pathological tenascin X protein caused by mutations in theTNXB gene located on chromosome 6p21.33-p21.32.

Major Criteria.

• Skin: Extremely elastic, velvety skin, which is fragile and easily damaged.
• Hematoma tendency
• General joint hypermobility with and without recurrent dislocations (shoulder, ankle).

Furthermore, "minor" criteria were defined:

• Acrogeria of the hands, piezogenic nodules.
• Orthopedic: hand and foot deformities (mallet finger, clinodactyly, plump forefoot, brachydactyly with wrinkling of the skin, pes planus, hallux valgus.
• Neuromuscular:mild proximal and distal muscle weakness, muscle atrophy in hands and feet, axonal polyneuropathy.

Other: acrogeria, non-cardiac leg edema, vagial-uterine-rectal prolapse.

1. Brady A et al (2017): Ehlers-Danlos Syndomes, rarer 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 Jourrnal of Medical Genetics 175C:40-47
5. Chopra P et al(2017): Pain management in the Ehlers-Danlos syndromes. American J
6. 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.