Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Ehlers-Danlos Syndrome with Tenascin-X Deficiency [Q79.6]

OMIM numbers: 606408, 600985 (TNXB)

Dr. rer. nat. Karin Mayer

Scientific Background

This rare EDS type with autosomal recessive inheritance does not belong to the 6 main types. Hyperextensible skin, hyperflexible joints and fragile tissue are characteristic, these represent also two main criteria for classical EDS. However, in contrast to the symptoms of patients with classical EDS no atrophic scarring or a prolonged wound healing occurs. Additional manifestations can be complications like diverticulitis, rectal prolapse, mitral valve prolapse and neuromuscular symptoms like myasthenia, hypotonia, myalgia, fatigue and paresthesia. 

The genetic cause of EDS with Tenascin-X deficiency was discovered in a patient with congenital adrenal hyperplasia and a 21-hydroxylase deficiency with additional clinical symptoms of classical EDS. Causal was a 30-kb deletion on chromosome 6p21.3, that both included the CYP21B gene and the partially overlapping TNXB gene, which constituted a contiguous gene syndrome. Homozygous or combined heterozygous mutations in TNXB, which lead to a total lack of the gene product Tenascin-X on the RNA and protein level, are causal for EDS with Tenascin-X deficiency. There is no more Tenascin-X detectable in the serum of the patients. Tenascin-X is a glycoprotein that is synthesized in the extracellular matrix of skin, tendons, muscles and blood vessels and it is secreted into the serum. So far only six different mutations have been identified in the TNXB gene. Some patients with Tenascin-X deficiency have myopathic symptoms that are characteristic for Bethlem myopathy or Ullrich muscular dystrophy. The lack of serum Tenascin-X leads to a decreased expression of type VI-collagen. 

The lack of serum Tenascin-X substantiates the clinical diagnosis.