Dermato-sparaxis ehlers-danlos syndromeQ79.6

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 (Brady A et al. 2017).

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).

The very rare Dermatosparaxis EDS is an autosomal recessive inherited, rare disease variant of the Ehlers-Danlos Syndrome (Malfait F et al. 2004)

Mutations in the ADAMTS2 gene can be detected. The ADAMTS2 gene (procollagen I N-proteinase gene) is located on chromosome 5q35.3 and codes for a procollagen I N-proteinase.

This enzyme cuts off a short chain of amino acids at one end of the procollagen. This "clipping step" is essential for the collagen molecules to be processed normally and to be able to assemble into fibrils outside the cells.

Clinical symptoms are classified according to major and minor criteria (Brinckmann J 2018).

Major symptoms are:

• Skin: Pronounced fragility with congenital or postpartum skin tears.
• Cutis laxa-likesymptomatology with severe wrinkling of wrists and ankles, increased skin wrinkling palmar
• Severe hematoma formation with risk of subcutaneous hematomas and hemorrhages
• Other: Characteristic facial physiognomy
• Umbilical hernias
• Growth retardation
• Perinatal complications due to tissue fragility
• Shortened hand and foot limbs

Minor criteria:

• Skin: soft doughy skin
• hyperelasticity, tissue fragility with atrophic scars
• Skeletal system: generalized hypermobility of joints
• Osteopenia
• Neuromuscular system: muscular hypotonia

Other:

• Visceral fragility (bladder and/or diaphragmatic ruptures, rectal prolapse, delayed motor development, hirsutism, dental anomalies, defective vision, strabismus.

Detection of the genetic defect

Clinical symptoms with extreme skin fragility + dysmorphia of the face.

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