Delayed Wound Healing in a Young Patient with TNXB Variants and the Role of WES

Abstract

After decades of quality improvement efforts, surgical site infections and abnormal wound healing remain intermittent complications in surgery. In both cases, the complication and abnormality may be superficial, restricted to the skin, or deeper within the tissue. The synthesis of connective tissue proteins, critical for structural support as part of the extracellular matrix, is under the control of multiple genes, forming a complex adaptive network. We report an unusual case of delayed and abnormal wound healing with chronic infection in a 16-year-old patient following surgery for scoliosis. Skin patch test showed that he is allergic to cobalt, a component of fixation hardware used in his surgery. He underwent evaluation by clinical genetics with whole exome sequencing (WES) which showed two (maternally and paternally inherited) variants in the TNXB ( Tenasin XB) gene. These two variants are variants of uncertain significance (VUS). TNXB encodes tenascin-XB which is an extracellular matrix glycoprotein located primarily in the basement membrane. Autosomal recessive pathogenic and likely pathogenic variants in TNXB cause TNXB-related classical-like Ehlers-Danlos Syndrome. At present, there are no causal linkages of these VUSs in TNXB to abnormal wound healing. However, as WES becomes more affordable, its use will increase and therefore it is important that we start to document such associations.