ESPE Abstracts (2021) 94 P2-33

1Departamento de Endocrinologia, Hospital das Forças Armadas (HFAR), Lisbon, Portugal; 2Unidade de Endocrinologia Pediátrica, Hospital de Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central (CHULC), Lisbon, Portugal; 3Unidade de Reumatologia Pediátrica, Hospital de Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central (CHULC), Lisbon, Portugal; 4Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal

Introduction: Congenital Adrenal Hyperplasia (CAH) is a group of genetic diseases characterized by impaired cortisol synthesis. 95% of CAH cases result from mutation in the CYP21A2 gene encoding 21-hydroxilase. TNX-B gene partially overlaps CYP21A2 and encodes a matrix protein called Tenascin-X (TNX). Complete tenascin deficiency causes Enlers-Danlos syndrome (EDS). A variant called CAH-X, has recently been described, resulting from CYP21A2 deletions extending into the TNXB on at least one allele. This haploinsufficiency of TNX may be associated with a mild hypermobility form of EDS, as well as other connective tissue comorbidities such as herniae, cardiac defects and chronic arthralgia. We report four patients heterozygous for a CAH-X allele that do not present clinical manifestations of the Ehlers-Danlos syndrome.

Case reports: Case 1: 18-year-old boy followed since classic salt wasting CAH presented in the newborn period. Molecular genetic testing confirmed the CAH diagnosis and identified (in heterozygosity) a CYP21A2 deletion overlapping the TNXB gene, giving rise to a TNXA/TNXB chimera. Neither clinical features of hypermobility or cardiac alterations were documented in this boy. At the age of 12 he was diagnosed with a testicular adrenal rest tumour.

Case 2: 14-year-old boy followed since the age of 7, when he was referred for evaluation due to precocious adrenarche. Endocrinologic parameters were compatible with non-classical CAH and genetic testing revealed a CYP21A2 variant and a complete CYP21A2 deletion on the other allele covering the last exons of TNXB. At physical exam he has a Beighton Score (BS) of 1 and history of joint disability. Cardiac defects were excluded.

Case 3: 12 year-old brother of Case 2, who was studied after index case diagnosis. Genetic testing revealed the same deletion; he is currently asymptomatic, without joint hypermobility, and with normal cardiologic evaluation. Case 4: 15 years old girl referred to endocrine paediatric department for secondary amenorrhea, without hirsutism or acne; elevated basal and post-stimulation 17-hydroxyprogesterone triggered genetic testing. A CYP21A2 deletion in one allele also affecting TNXB was identified. She has no clinical features of connective tissue disorders, and cardiac defects were also excluded.

Conclusion: These 4 CAH cases with a monoallelic CYP21A2 deletion overlapping the Tenascin-X gene, highlight the importance of additional clinical evaluations related with the recently described CAH-X Syndrome. CAH patients, carriers of these TNXA/TNXB chimeras, should be evaluated for clinical manifestations related to connective tissue hypermobility, cardiac abnormalities and other EDS features allowing a better clinical management.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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