The autosomal recessively inherited musculocontractural EDS (mcEDS) is genetically heterogeneous and in the 1998 Villfranche classification was included in the group of kyphoscoliotic EDS with inconspicuous LP/HP ratio (EDS type VIB). Today, a distinction is made between mcEDS patients with a D4ST1 deficiency (type 1) and mcEDS patients with a DSE deficiency (type 2).
mcEDS is a differential diagnosis to neuromuscular diseases within the group of connective tissue diseases. It is characterized by an asthenic physique, instability of the large joints, tapering fingers , brachycephaly and characteristic facial features, hyperextensible and fragile skin, and recurrent subcutaneous hematomas.
The molecular cause of D4ST1 deficiency (mcEDS type 1) is homozygous or combined heterozygous variants in the CHST14 gene (carbohydrate sulfotransferase 14), which encodes dermatan 4-O-sulfotransferase 1 (D4ST1). The molecular cause of DSE deficiency (mcEDS type 2) is homozygous or combined heterozygous variants in the DSE gene encoding dermatan sulfate epimerase (DSE). Both enzymes are involved in dermatan sulfate biosynthesis. DSE catalyzes the epimerization of D‑glucuronic acid (D-GlcA) to L-iduronic acid (L-IdoA) allowing D4ST1 to catalyze the 4-O-sulfonation of N-acetyl-D-galactosamine.
Brady et al. 2017, Am J Med Genet C 175:70 / Van Damme et al. 2016, Genet Med 18:882 / Colige et al. 2004, J Invest Dermatol 123:656 / Malfait et al. 2004, Am J Med Genet 131A:18