Endocrine Abstracts

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is encoded by the CYP21A2 gene. The CYP21A2 gene is partially overlapped by the TNXB gene encoding an extracellular matrix protein called Tenascin-X. Deficiency of Tenascin X can cause the Ehlers-Danlos Syndrome (EDS). Deletions of CYP21A2 extending into TNXB rarely cause CAH combined with EDS. CAH associated with mild hypermobility form of EDS due to TNXB haploinsufficiency caused by heterozygous mutation has been named CAH-X syndrome. We genetically investigated a cohort of 81 patients (31 males, mean age 37.8 years ± 9.8) with classic CAH for CAH-X. Patients genetically positive for CAH-X and unaffected CAH control patients matched for sex, age and BMI underwent a thorough clinical investigation including joint examination by Beighton 9-point scale, skin and neurological examination, by a standardised protocol of thransthoracic echocardiography and muscle ultrasound. In addition serum tenascin-X has been measured. We identified one patient with CAH and EDS and 4 patients with CAH-X. All CAH-X patients had concentrations of tenascin-X below the normal range, but not different from 35 unaffected CAH patients. All 4 patients with CAH-X showed some associated clinical symptoms. Two had joint hypermobility detected by Beighton 9-point score. Two CAH-X patients showed cardiac abnormalities. The patient with CAH and EDS showed cardiac abnormalities and typical EDS symptoms. All affected patients complained about back pain and showed foot malposition. Profound changes in muscle ultrasound were found in 60 % of patients with CAH-X syndrome (3/5) and in none of the controls (0/5). In conclusion, our data confirm the previously described prevalence of CAH-X. Beighton-score seems to be a quick and cheap screening instrument for CAH-X and should be performed in all patients with classic CAH, since protein level in serum cannot be used for screening for CAH-X-Syndrome. A stronger focus needs to be made on back pain and foot malposition as symptoms of CAH-X and echocardiography should be performed in all CAH-X patients. Therapy should depend on clinical symptoms.