AbstractObjectiveApproximately 10% of patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency carry a mutation that disruptsCYP21A2and the flankingTNXBgene resulting in CAH-X, a contiguous gene deletion syndrome.TNXBencodes tenascin-X (TNX), an extracellular matrix glycoprotein that plays an important role in collagen organization.TNXBimpairment is associated with Ehlers–Danlos syndrome. Symptoms include joint hypermobility, hernias and cardiac defects. We measured serum TNX using an antibody targeting the amino-terminal of the TNX protein in 161 subjects, including extensively genotyped and phenotyped CAH patients, their relatives, and healthy controls.ResultsWe evaluated the potential of serum TNX as a screening tool for CAH-X. CAH-X patients, especially haploinsufficient patients carrying theTNXA-TNXBchimeric gene CAH-X-CH-1 showed reduced TNX levels compared to controls (P < 0.05). TNX levels were similar in all subjects carrying aTNXBmutation. However, CAH patients who did not harbor aTNXBmutation also had reduced TNX compared to controls (P < 0.001). Thus, measuring serum TNX is not an effective screen for CAH-X amongst patients with CAH.TNXBgenotyping is recommended for CAH patients who have symptoms of a connective tissue disorder. Epigenetic factors that influence TNX expression require further study.