Novel cardiac abnormalities observed in CAH patients with tenascin-X haploinsufficiency.

BACKGROUND

Defects in both CYP21A2 and TNXB genes cause congenital adrenal hyperplasia combined with hypermobility-type Ehlers-Danlos syndrome (EDS), which has been named CAH-X syndrome.

OBJECTIVE

This study aimed to determine the frequency of CAH-X within the Munich cohort of CAH patients (n = 155: salt wasting = 94, simple virilizing = 44, non-classical = 12, gene carrier = 4, 11β-deficiency = 1) and assess its clinical implications by thorough clinical characterization of the cohort. In addition, sTNXB protein levels were linked to clinical observations to alleviate potential consequences of mutations such as cardiovascular or joint problems.

DESIGN/SETUP: PCR screening for the presence of disease-causing variants in TNXB as well as in CYP21A2 (n = 155) was conducted; simultaneously, with written consent from the patients (n = 76), clinical examinations for joint or skin abnormalities, muscle strength, and neurological functions were performed. CAH-X-positive patients were matched to two control CAH patients according to age and body mass index (BMI). sTNXB protein level estimation, muscle ultrasound, and echocardiography examinations were made on selected CAH-X and CAH patients.

OUTCOME/

CONCLUSION

In our cohort, only 5% carry the CAH-X CH1 chimera. Besides EDS-related clinical symptoms, increased muscle echogenicity compared to unaffected matched controls, particularly in the legs, and cardiac abnormalities that have not been observed in other cohorts and are associated with underlying CAH-X, such as persistent truncus arteriosus and relaxation disorder, were observed. They highlight the importance of genetic as well as clinical screening and regular follow-up examinations for the CAH-X syndrome.