AUTHOR=Marino Roxana , Moresco Angélica , Perez Garrido Natalia , Ramirez Pablo , Belgorosky Alicia 

TITLE=Congenital Adrenal Hyperplasia and Ehlers-Danlos Syndrome

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.803226

DOI=10.3389/fendo.2022.803226

ISSN=1664-2392

ABSTRACT=<p>Congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency is an autosomal recessive disorder. The 21-hydroxylase enzyme P450c21 is encoded by the <italic>CYP21A2</italic> gene located on chromosome 6p21.33 within the HLA major histocompatibility complex. This locus also contains the <italic>CYP21A1P</italic>, a non-functional pseudogene, that is highly homologous to the <italic>CYP21A2</italic> gene. Other duplicated genes are <italic>C4A</italic> and <italic>C4B</italic>, that encode two isoforms of complement factor C4, the <italic>RP1</italic> gene that encodes a serine/threonine protein kinase, and the <italic>TNXB</italic> gene that, encodes the extracellular matrix glycoprotein tenascin-X (TNX). TNX plays a role in collagen deposition by dermal fibroblasts and is expressed in the dermis of the skin and the connective tissue of the heart and skeletal muscle. During meiosis, misalignment may occur producing large gene deletions or gene conversion events resulting in chimeric genes. Chimeric recombination may occur between <italic>TNXB</italic> and <italic>TNXA.</italic> Three <italic>TNXA/TNXB</italic> chimeras have been described that differ in the junction site (CH1 to CH3) and result in a contiguous <italic>CYP21A2</italic> and <italic>TNXB</italic> gene deletion, causing CAH-X syndrome. <italic>TNXB</italic> deficiency is associated with Ehlers Danlos syndrome (EDS). EDS comprises a clinically and genetically heterogeneous group of connective tissue disorders. As molecular analysis of the <italic>TNXB</italic> gene is challenging, the TNX-deficient type EDS is probably underdiagnosed. In this minireview, we will address the different strategies of molecular analysis of the <italic>TNXB</italic>-gene, as well as copy number variations and genetic status of <italic>TNXB</italic> in different cohorts. Furthermore, clinical features of EDS and clinical recommendations for long-term follow-up are discussed.</p>