Analysis of obstetric complications and uterine connective tissue in tenascin-X-deficient humans and mice

Abstract

Tenascin-X (TNX) is a large, multi-domain, extracellular matrix glycoprotein. Complete deficiency of TNX in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), and TNX haploinsufficiency is a cause of hypermobility type EDS. EDS patients appear to have a higher risk of several complications during pregnancy, such as pelvic instability, premature rupture of membranes, and postpartum hemorrhage. Here, we present a study of genitourinary and obstetric complications in TNX-deficient women of reproductive age. We have found complications, such as uterus prolapses, that are in agreement with previous findings in other EDS types. In TNX knockout (KO) mice, we have observed mild pregnancy-related abnormalities. Morphological and immunohistological analysis of uterine tissues has not revealed obvious quantitative or spatial differences between TNX KO and wildtype mice with respect to collagen types I, III, V, and XII or elastic fibers. We conclude that TNX-deficient women are at risk of obstetric complications, but that TNX KO mice show only a mild phenotype. Furthermore, we show that TNX is involved in the stability of elastic fibers rather than in their initial deposition.

Tenascin-X deficiency and Ehlers-Danlos syndrome: a case report and review of the literature

“…A number of patients with tenascin‐X deficiency have also been identified with gastrointestinal complications, particularly diverticulosis and rectal prolapse 17 . The gynaecological/obstetric complications reported include uterine and vaginal prolapse most likely due to decreased tone within the vaginal canal 17 .…”

Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type

“…[15][16][17] Heterozygotes for the same mutation, especially females, appear to have an EDS hypermobility phenotype.…”

Recognizing the tenascin‐X deficient type of Ehlers–Danlos syndrome: a cross‐sectional study in 17 patients

“…After the initial publication, additional cases have been reported, with a focus on specific clinical features, including neuromuscular, genito-urethral, gastrointestinal, and cardiovascular findings (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). So far, of 14 families only 18 patients with TNX-deficiency and two 2 with the contiguous gene syndrome have been reported, 14 of whom from the Netherlands.…”