Molecular characterization of the new clinical entity associated with congenital adrenal hyperplasia: the CAH-X syndrome in the Spanish population.

Objectives: The chimeras causing the CAH-X syndrome (SCAH-X) result from recombination between CYP21A2-TNXB and their respective pseudogenes (CYP21A1P-TNXA). The clinical manifestations of this syndrome include congenital adrenal hyperplasia (CAH) and Ehlers-Danlos syndrome (EDS). Since SCAH-X has been recently described, the number of publications available is limited. The objective of this study was to set up a molecular approach and a screening algorithm for detecting CAH-X chimeras, determine their frequency and distribution in the Spanish population, and assess their clinical pattern of occurrence in a group of patients. Methods: A total of 186 patients were eligible for CAH-X molecular genetic testing. Testing included MLPA, heterodimer detection by capillary gel electrophoresis, and sequencing of exons 40, 41, and 43 of TNXB. A review was performed of the medical history of 20 patients from three hospitals of reference and the signs and symptoms of EDS they exhibited. Results: In total, 78 CAH patients were carriers of CAH-X chimeras (41.9 %). Forty-six patients were carriers of CH1 (24.7 %), 24 of CH2 (12.9 %), and 8 of CH3 (4.3 %), with a heterogeneous geographical distribution. Seven (35 %) of the 20 carriers of a CAH-X chimera who underwent clinical examination experienced clinical manifestations of EDS. Conclusions: The impact of SCAH-X in the Spanish population was assessed by genetic testing. In the light of the clinical pattern of occurrence and significant prevalence of SCAH-X in the Spanish population, early diagnosis of this entity is essential for an appropriate follow-up of clinical manifestations.