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Background <p>Tatton‑Brown‑Rahman syndrome (TBRS) is an ultra-rare overgrowth and neurodevelopmental disorder caused by germline <i>DNMT3A</i> variants. Neoplastic manifestations are rarely reported; consequently, data regarding tumor susceptibility in this condition remain limited. Low-grade fibromyxoid sarcoma (LGFMS) has not been previously reported in individuals with TBRS.</p> Case presentation <p>We report a 20‑year‑old male with clinical features of TBRS and a heterozygous germline <i>DNMT3A</i> NM_022552.5:c.1904G &gt; A (p.Arg635Gln) variant, inherited from his father. The patient developed LGFMS at the age of 17 years. Histopathological and immunohistochemical findings supported the diagnosis. Molecular analysis confirmed the <i>DNMT3A</i> variant in blood and tumor tissue without loss of heterozygosity (LOH) by Sanger-based allelic comparison. Segregation analysis identified the variant in the affected father and sister, supporting pathogenicity and confirming familial transmission.</p> Conclusions <p>This case documents the first familial transmission of the <i>DNMT3A</i> c.1904G &gt; A (p.Arg635Gln) variant in a Brazilian family, and describes the first reported co-occurrence of TBRS and LGFMS. While causality remains unproven, this finding suggests that germline disruption of epigenetic regulators may influence tumor susceptibility.</p>

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Co-occurrence of low-grade fibromyxoid sarcoma and familial Tatton-Brown-Rahman syndrome with germline DNMT3A c.1904G > A (p.Arg635Gln): a case report

  • 期刊论文

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  • 发表日期：

    2026年7月2日

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  • Luana Diniz Guerra Braz,
  • Renan Gomes,
  • Fabiane Carvalho de Macedo,
  • Gabriel Lanes Cypriano,
  • Vanessa Mendonça,
  • Barbara da Costa Reis Monte-Mór,
  • Sima Ferman,
  • Anna Cláudia Evangelista dos Santos

摘要

Background

Tatton‑Brown‑Rahman syndrome (TBRS) is an ultra-rare overgrowth and neurodevelopmental disorder caused by germline DNMT3A variants. Neoplastic manifestations are rarely reported; consequently, data regarding tumor susceptibility in this condition remain limited. Low-grade fibromyxoid sarcoma (LGFMS) has not been previously reported in individuals with TBRS.

Case presentation

We report a 20‑year‑old male with clinical features of TBRS and a heterozygous germline DNMT3A NM_022552.5:c.1904G > A (p.Arg635Gln) variant, inherited from his father. The patient developed LGFMS at the age of 17 years. Histopathological and immunohistochemical findings supported the diagnosis. Molecular analysis confirmed the DNMT3A variant in blood and tumor tissue without loss of heterozygosity (LOH) by Sanger-based allelic comparison. Segregation analysis identified the variant in the affected father and sister, supporting pathogenicity and confirming familial transmission.

Conclusions

This case documents the first familial transmission of the DNMT3A c.1904G > A (p.Arg635Gln) variant in a Brazilian family, and describes the first reported co-occurrence of TBRS and LGFMS. While causality remains unproven, this finding suggests that germline disruption of epigenetic regulators may influence tumor susceptibility.