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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
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Novel cardiac abnormalities observed in CAH patients with tenascin-X haploinsufficiency

Andrea Sappl1, Annie M Sriramachandran1, Christian Lottspeich1

  • 1Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universität München, Munich, Germany.

Frontiers in Endocrinology
|June 1, 2026
PubMed

Insights

Congenital adrenal hyperplasia with Ehlers-Danlos syndrome (CAH-X) occurs in 5% of CAH patients. This syndrome presents with EDS symptoms, increased muscle echogenicity, and unique cardiac abnormalities, necessitating genetic and clinical screening.

Area of Science:

  • Genetics and Molecular Biology
  • Endocrinology
  • Rheumatology

Background:

  • Congenital adrenal hyperplasia (CAH) combined with hypermobility-type Ehlers-Danlos syndrome (EDS) is caused by defects in both the *CYP21A2* and *TNXB* genes, termed CAH-X syndrome.
  • CAH-X syndrome presents a complex interplay between endocrine dysfunction and connective tissue abnormalities.

Purpose of the Study:

  • To determine the frequency of CAH-X in a Munich cohort of CAH patients.
  • To assess the clinical implications of CAH-X through thorough characterization.
  • To correlate soluble TNXB (sTNXB) protein levels with clinical observations to understand potential consequences like cardiovascular or joint issues.

Main Methods:

  • PCR screening for disease-causing variants in *TNXB* and *CYP21A2* genes in 155 CAH patients.
  • Clinical examinations of 76 patients for joint, skin, muscle, and neurological abnormalities.
  • Matched case-control study comparing CAH-X patients with CAH controls, including sTNXB level estimation, muscle ultrasound, and echocardiography.

Main Results:

  • The CAH-X CH1 chimera was identified in 5% of the cohort.
  • CAH-X patients exhibited EDS-related symptoms, increased muscle echogenicity (especially in legs), and unique cardiac abnormalities like persistent truncus arteriosus and relaxation disorder.
  • These cardiac findings were not previously reported in other CAH cohorts.

Conclusions:

  • CAH-X syndrome requires comprehensive genetic and clinical screening.
  • Regular follow-up examinations are crucial for managing the diverse clinical manifestations of CAH-X.
  • The study highlights the importance of investigating genetic underpinnings for complex syndromic presentations.
Abstract

Keywords:
CAH-X syndromeEhlers-Danlos syndromechimeric TNXA/TNXB genecongenital adrenal hyperplasiatenascin X haploinsufficiency

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